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Open Access 01-02-2020 | Insulins | Neurology and Preclinical Neurological Studies - Review Article

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

Authors: Jelena Osmanovic Barilar, Ana Knezovic, Ana Babic Perhoc, Jan Homolak, Peter Riederer, Melita Salkovic-Petrisic

Published in: Journal of Neural Transmission | Issue 2/2020

Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and co-expression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.

Abramov AY, Duchen MR (2005) The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides. Philos Trans R Soc Lond B Biol Sci 360:2309–2314PubMedPubMedCentral

Afshin-Majd S, Bashiri K, Kiasalari Z, Baluchnejadmojarad T, Sedaghat R, Roghani M (2017) Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson's disease in the rat. Biomed Pharmacother 89:1–9PubMed

Agrawal R, Mishra B, Tyagi E, Nath C, Shukla R (2010) Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharmacol Res 61:247–252PubMed

Albers MW, Gilmore GC, Kaye J et al (2015) At the interface of sensory and motor dysfunctions and Alzheimer's disease. Alzheimers Dement 11:70–98PubMed

Allard P, Alafuzoff I, Carlsson A, Eriksson K, Ericson E, Gottfries CG, Marcusson JO (1990) Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease. Eur Neurol 30:181–185PubMed

Amin J, Paquet C, Baker A, Asuni AA, Love S, Holmes C, Hugon J, Nicoll JA, Boche D (2015) Effect of amyloid-β (Aβ) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3β. Neuropathol Appl Neurobiol 41:445–457PubMed

Amiri S, Haj-Mirzaian A, Momeny M, Amini-Khoei H, Rahimi-Balaei M, Poursaman S, Rastegar M, Nikoui V, Mokhtari T, Ghazi-Khansari M, Hosseini MJ (2017) Streptozotocin induced oxidative stress, innate immune system responses and behavioural abnormalities in male mice. Neuroscience 340:373–383PubMed

An Y, Varma VR, Varma S et al (2018) Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement 14:318–329PubMed

Angelova PR, Abramov AY (2016) Functional role of mitochondrial reactive oxygen species in physiology. Free Radic Biol Med 100:81–85PubMed

Anitha M, Abraham PM, Paulose CS (2012) Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: effect of pyridoxine treatment. Eur J PharmacolDec 696:54–61

Arluison M, Quignon M, Nguyen P, Thorens B, Leloup C, Penicaud L (2004) Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain—an immunohistochemical study. J Chem Neuroanat 28:117–136PubMed

Arora R, Deshmukh R (2017) Embelin attenuates intracerebroventricular streptozotocin-induced behavioral, biochemical, and neurochemical abnormalities in rats. Mol Neurobiol 54:6670–6680PubMed

Athauda D, Foltynie T (2016) The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action. Drug Discov Today 21:802–818PubMed

Babic Perhoc A, Osmanovic Barilar J, Knezovic A, Farkas V, Bagaric R, Svarc A, Grünblatt E, Riederer P, Salkovic-Petrisic M (2019) Cognitive, behavioral and metabolic effects of oral galactose treatment in the transgenic Tg2576 mice. Neuropharmacology 148:50–67PubMed

Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer's disease. Lancet 377:1019–1031PubMed

Barilar JO, Knezovic A, Grünblatt E, Riederer P, Salkovic-Petrisic M (2015) Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease. J Neural Transm (Vienna) 122:565–576

Becker B, Demirbas M, Johann S, Zendedel A, Beyer C, Clusmann H, Haas SJ, Wree A, Tan SKH, Kipp M (2018) Effect of intrastriatal 6-OHDA lesions on extrastriatal brain structures in the mouse. Mol Neurobiol 55:4240–4252PubMed

Biosa A, Outeiro TF, Bubacco L, Bisaglia M (2018) Diabetes mellitus as a risk factor for Parkinson's disease: a molecular point of view. Mol Neurobiol 55:8754–8763PubMed

Biswas J, Gupta S, Verma DK, Gupta P, Singh A, Tiwari S, Goswami P, Sharma S, Singh S (2018) Involvement of glucose related energy crisis and endoplasmic reticulum stress: insinuation of streptozotocin induced Alzheimer's like pathology. Cell Signal 42:211–226PubMed

Bloom GS, Lazo JS, Norambuena A (2018) Reduced brain insulin signaling: a seminal process in Alzheimer's disease pathogenesis. Neuropharmacology 136:192–195PubMed

Bolzán AD, Bianchi MS (2002) Genotoxicity of streptozotocin. Mutat Res. 512:121–134PubMed

Bonito-Oliva A, Pignatelli M, Spigolon G, Yoshitake T, Seiler S, Longo F et al (2014) Cognitive impairment and dentate gyrus synaptic dysfunction in experimental Parkinsonism. Biol Psychiatry 75:701–710PubMed

Bordey A, Sontheimer H (2000) Ion channel expression by astrocytes in situ: comparison of different CNS regions. Glia 30:27–38PubMed

Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24:197–211PubMed

Brooks DJ (2010) Examining Braak's hypothesis by imaging Parkinson's disease. Mov Disord 25:S83–88PubMed

Brownell AL, Canales K, Chen YI, Jenkins BG, Owen C, Livni E, Yu M, Cicchetti F, Sanchez-Pernaute R, Isacson O (2003) Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model. Neuroimage 20:1064–1075PubMed

Budni J, Feijó DP, Batista-Silva H, Garcez ML, Mina F, Belletini-Santos T, Krasilchik LR, Luz AP, Schiavo GL, Quevedo J (2017) Lithium and memantine improve spatial memory impairment and neuroinflammation induced by β-amyloid 1–42 oligomers in rats. Neurobiol Learn Mem 141:84–92PubMed

Burwinkel M, Lutzenberger M, Heppner FL, Schulz-Schaeffer W, Baier M (2018) Intravenous injection of beta-amyloid seeds promotes cerebral amyloid angiopathy (CAA). Acta Neuropathol Commun 6:23PubMedPubMedCentral

Caballol N, Martí MJ, Tolosa E (2007) Cognitive dysfunction and dementia in Parkinson disease. Mov Disord 17:S358–366

Casteels C, Lauwers E, Bormans G, Baekelandt V, Van Laere K (2008) Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson's disease. Eur J Nucl Med Mol Imaging 35:124–134PubMed

Castro AA, Wiemes BP, Matheus FC, Lapa FR, Viola GG, Santos AR, Tasca CI, Prediger RD (2013) Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson's disease. Brain Res 1513:103–116PubMed

Chen Z, Zhong C (2013) Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol 108:21–43PubMed

Chen HH, Chang PC, Chen C, Chan MH (2018a) Protective and therapeutic activity of honokiol in reversing motor deficits and neuronal degeneration in the mouse model of Parkinson's disease. Pharmacol Rep 70:668–676PubMed

Chen Y, Guo Z, Mao YF, Zheng T, Zhang B (2017) Intranasal insulin ameliorates cerebral hypometabolism, neuronal loss, and astrogliosis in streptozotocin-induced Alzheimer's rat model. Neurotox Res 33:716–724PubMed

Chen Y, Guo Z, Mao YF, Zheng T, Zhang B (2018b) Intranasal insulin ameliorates cerebral hypometabolism, neuronal loss, and astrogliosis in streptozotocin-induced Alzheimer’s rat model. Neurotox Res 33:716–724PubMed

Churchill MJ, Pflibsen L, Sconce MD, Moore C, Kim K, Meshul CK (2017) Exercise in an animal model of Parkinson’s disease: motor recovery but not restoration of the nigrostriatal pathway. Neuroscience 359:224–247PubMed

Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O (2001) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991–998

Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S (2015) Long acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis. 45:1269–1270PubMed

Correia SC, Santos RX, Santos MS, Casadesus G, Lamanna JC, Perry G, Smith MA, Moreira PI (2013) Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer's disease. Curr Alzheimer Res 10:406–419PubMed

Costa G, Simola N, Morelli M (2014) MDMA administration during adolescence exacerbates MPTP-induced cognitive impairment and neuroinflammation in the hippocampus and prefrontal cortex. Psychopharmacology 231:4007–4018PubMed

Costa M, Bernardi J, Fiuza T, Costa L, Brandão R, Pereira ME (2016) N-Acetylcysteine protects memory decline induced by streptozotocin in mice. Chem Biol Interact 253:10–17PubMed

Crabbé M, Van der Perren A, Bollaerts I, Kounelis S, Baekelandt V, Bormans G, Casteels C, Lieve Moons L, Van Laere K (2019) Increased P2X7 receptor binding is associated with neuroinflammation in acute but not chronic rodent models for Parkinson’s disease. Front Neurosci 13:799PubMedPubMedCentral

Da Cunha C, Wietzikoski S, Wietzikoski EC, Miyoshi E, Ferro MM, Anselmo-Franci JA, Canteras NS (2003) Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system. Neurobiol Learn Mem 79:236–242PubMed

Da Cunha C, Silva MH, Wietzikoski S, Wietzikoski EC, Ferro MM, Kouzmine I, Canteras NS (2006) Place learning strategy of substantia nigra pars compacta-lesioned rats. Behav Neurosci 120:1279–1284PubMed

Datta I, Ganapathy K, Razdan R, Bhonde R (2018) Location and number of astrocytes determine dopaminergic neuron survival and function under 6-OHDA stress mediated through differential BDNF release. Mol Neurobiol 55:5505–5525PubMed

Davie CA (2008) A review of Parkinson's disease. Br Med Bull 86:109–127PubMed

de la Monte SM, Tong M (2014) Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol 88:548–559PubMed

Defelice FG, Ferreira ST (2002) Physiopathological modulators of amyloid aggregation and novel pharmacological approaches in Alzheimer's disease. An Acad Bras Cienc 74:265–284PubMed

Deng Y, Li B, Liu Y, Iqbal K, Grundke-Iqbal I, Gong CX (2009) Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: implication for Alzheimer’s disease. Am J Pathol 175:2089–2098PubMedPubMedCentral

Ding A, Nitsch R, Hoyer S (1992) Changes in brain monoaminergic neurotransmitter concentrations in rat after intracerebroventricular injection of streptozotocin. J Cereb Blood Flow Metab 12:103–109PubMed

Dos Santos JPA, Vizuete A, Hansen F, Biasibetti R, Gonçalves CA (2018) Early and persistent O-GlcNAc protein modification in the streptozotocin model of Alzheimer's disease. J Alzheimers Dis 61:237–249PubMed

Dwyer DS, Vannucci SJ, Simpson IA (2002) Expression, regulation, and functional role of glucose transporters (GLUTs) in brain. Int Rev Neurobiol 51:159–188PubMed

Eisele YS, Bolmont T, Heikenwalder M, Langer F, Jacobson LH, Yan ZX, Roth K, Aguzzi A, Staufenbiel M, Walker LC, Jucker M (2009) Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci USA 106:12926–21231PubMed

Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M (2010) Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science 330:980–982PubMedPubMedCentral

Eisele YS, Fritschi SK, Hamaguchi T, Obermüller U, Füger P, Skodras A, Schäfer C, Odenthal J, Heikenwalder M, Staufenbiel M, Jucker M (2014) Multiple factors contribute to the peripheral induction of cerebral β-amyloidosis. J Neurosci 34:10264–10273PubMedPubMedCentral

Eleazu CO, Eleazu KC, Chukwuma S, Essien UN (2013) Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord 12:60PubMedPubMedCentral

Engelender S, Isacson O (2017) The threshold theory for Parkinson's disease. Trends Neurosci 40:4–14PubMed

Facchinetti R, Bronzuoli MR, Scuderi C (2018) An animal model of Alzheimer disease based on the intrahippocampal injection of amyloid β-peptide (1–42). Methods Mol Biol 1727:343–352PubMed

Falardeau P, Bédard PJ, Di Paolo T (1988) Relation between brain dopamine loss and D2 dopamine receptor density in MPTP monkeys. Neurosci Lett 86:225–229PubMed

Falquetto B, Tuppy M, Potje SR, Moreira TS, Antoniali C, Takakura AC (2017) Cardiovascular dysfunction associated with neurodegeneration in an experimental model of Parkinson's disease. Brain Res 1657:156–166PubMed

Femminella GD, Edison P (2014) Evaluation of neuroprotective effect of glucagon-like peptide 1 analogs using neuroimaging. Alzheimers Dement 10:S55–61PubMed

Feng XY, Yang J, Zhang X, Zhu J (2019) Gastrointestinal non-motor dysfunction in Parkinson's disease model rats with 6-hydroxydopamine. Physiol Res 68:295–303PubMed

Fernandez-Ruiz J, Doudet DJ, Aigner TG (1995) Long-term cognitive impairment in MPTP-treated rhesus monkeys. NeuroReport 7:102–104PubMed

Fifel K, Dkhissi-Benyahya O, Cooper HM (2013) Lack of long-term changes in circadian, locomotor, and cognitive functions in acute and chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse models of Parkinson's disease. Chronobiol Int 30:741–755PubMed

Figlewicz DP, Evans SB, Murphy J, Hoen M, Baskin DG (2003) Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat. Brain Res 964:107–115PubMed

Foffani G, Obeso JA (2018) A cortical pathogenic theory of Parkinson's disease. Neuron 99:1116–1128PubMed

Fulceri F, Biagioni F, Lenzi P, Falleni A, Gesi M, Ruggieri S, Fornai F (2006) Nigrostriatal damage with 6-OHDA. Cell 166:867–880

Gai W, Schott-Ohly P, Schulte IM, Walde S, Gleichmann H (2004) Differential target molecules for toxicity induced by streptozotocin and alloxan in pancreatic islets of mice in vitro. Exp Clin Endocrinol Diabetes 112:29–37PubMed

Garabadu D, Verma J (2019) Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt dependent pathway in amyloid beta (1–42)-induced cognitive deficit rats. Neurochem Int 128:39–49PubMed

García-Cáceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P et al (2016) Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166:867–880PubMed

Garcia-Tornadú I, Perez-Millan MI, Recouvreux V, Ramirez MC, Luque G, Risso GS, Ornstein AM, Cristina C, Diaz-Torga G, Becu-Villalobos D (2010) New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2 mouse. Neuroendocrinology 92:207–214PubMed

Gerhart DZ, Leino RL, Borson ND, Taylor WE, Gronlund KM, McCall AL, Drewes LR (1995) Localization of glucose transporter GLUT 3 in brain: comparison of rodent and dog using species-specific carboxyl-terminal antisera. Neuroscience 66:237–246PubMed

Gibb WR, Lees AJ, Jenner P, Marsden CD (1986) The dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces histological lesions in the hypothalamus of the common marmoset. Neurosci Lett 65:79–83PubMed

Goes AT, Souza LC, Filho CB, Del Fabbro L, De Gomes MG, Boeira SP, Jesse CR (2014) Neuroprotective effects of swimming training in a mouse model of Parkinson's disease induced by 6-hydroxydopamine. Neuroscience 256:61–71PubMed

Goes ATR, Jesse CR, Antunes MS, Lobo Ladd FV, Lobo Ladd AAB, Luchese C, Paroul N, Boeira SP (2018) Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson's disease: involvement of neuroinflammation and neurotrophins. Chem Biol Interact 279:111–120PubMed

Graham WC, Clarke CE, Boyce S, Sambrook MA, Crossman AR, Woodruff GN (1990) Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis). Brain Res 514:103–110PubMed

Gratwicke J, Jahanshahi M, Foltynie T (2018) Parkinson’s disease dementia: a neural networks perspective. Brain 138:1454–1476

Grospe GM, Baker PM, Ragozzino ME (2018) Cognitive flexibility deficits following 6-OHDA lesions of the rat dorsomedial striatum. Neuroscience 374:80–90PubMed

Gruenblatt E, Salkovic-Petrisic M, Osmanovic J, Riederer P, Hoyer S (2007) Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem 101:757–770

Guerra de Souza AC, Gonçalves CL, de Souza V, Hartwig JM, Farina M, Prediger RD (2018) Agmatine attenuates depressive-like behavior and hippocampal oxidative stress following amyloid β (Aβ1-40) administration in mice. Behav Brain Res 353:51–56PubMed

Gupta S, Yadav K, Mantri SS, Singhal NK, Ganesh S, Sandhir R (2018) Evidence for compromised insulin signaling and neuronal vulnerability in experimental model of sporadic Alzheimer's disease. Mol Neurobiol 55:8916–8935PubMed

Haddadi R, Poursina M, Zeraati F, Nadi F (2018) Gastrodin microinjection suppresses 6-OHDA-induced motor impairments in parkinsonian rats: insights into oxidative balance and microglial activation in SNc. Inflammopharmacology 26:1305–1316PubMed

Haga H, Matsuo K, Yabuki Y, Zhang C, Han F, Fukunaga K (2019) Enhancement of ATP production ameliorates motor and cognitive impairments in a mouse model of MPTP-induced Parkinson's disease. Neurochem Int 129:104492PubMed

Han Z, Tian R, Ren P, Zhou W, Wang P, Luo M, Jin S (2018) Parkinson’s disease and Alzheimer’s disease: a Mendelian randomization study. BMC Med Genet 19:215PubMedPubMedCentral

Harkany T, Hortobágyi T, Sasvári M, Kónya C, Penke B, Luiten PG, Nyakas C (1999) Neuroprotective approaches in experimental models of beta-amyloid neurotoxicity: relevance to Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 23:963–1008PubMed

Heo JH, Lee SR, Lee ST, Lee KM, Oh JH, Jang DP, Chang KT, Cho ZH (2011) Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. J Alzheimers Dis 25:517–523PubMed

Hill JM, Lesniak MA, Pert CB, Roth J (1986) Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience 17:1127–1138PubMed

Horita KT, Kobayashi M, Mori A, Jenner P, Kanda T (2015) Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacology 230:345–352

Hoyer S (2004) Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 490:115–125PubMed

Hu D, Cao Y, He R, Han N, Liu Z, Miao L, Yin J (2012) Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates Aβ1-42-induced memory impairment in mice. Oxid Med Cell Longev 2012:721721PubMedPubMedCentral

Hu M, Li F, Wang W (2018) Vitexin protects dopaminergic neurons in MPTP-induced Parkinson’s disease through PI3K/Akt signaling pathway. Drug Des Devel Ther 12:565–573PubMedPubMedCentral

Isaev NK, Genrikhs EE, Voronkov DN, Kapkaeva MR, Stelmashook EV (2018) Streptozotocin toxicity in vitro depends on maturity of neurons. Toxicol Appl Pharmacol 348:99–104PubMed

Jafari A, Noursadeghi E, Khodagholi F, Saghiri R, Sauve R, Aliaghaei A, Eliassi A (2015) Brain mitochondrial ATP-insensitive large conductance Ca²⁺-activated K⁺ channel properties are altered in a rat model of amyloid-β neurotoxicity. Exp Neurol 269:8–16PubMed

Jang DP, Min HK, Lee SY, Kim IY, Park HW, Im YH, Lee S, Sim J, Kim YB, Paek SH, Cho ZH (2012) Functional neuroimaging of the 6-OHDA lesion rat model of Parkinson's disease. Neurosci Lett 513:187–192PubMed

Javed H, Vaibhav K, Ahmed ME, Khan A, Tabassum R, Islam F, Safhi MM, Islam F (2015) Effect of hesperidin on neurobehavioral, neuroinflammation, oxidative stress and lipid alteration in intracerebroventricular streptozotocin induced cognitive impairment in mice. J Neurol Sci 348:51–59PubMed

Javitch JA, D'Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177PubMed

Jayant S, Sharma BM, Sharma B (2016) Protective effect of transient receptor potential vanilloid subtype 1 (TRPV1) modulator, against behavioral, biochemical and structural damage in experimental models of Alzheimer's disease. Brain Res 1642:397–408PubMed

Jellinger KA (2019) Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update-I. Hypokinetic-rigid movement disorders. J Neural Transm (Vienna) 126:933–995

Jing H, Wang S, Wang M, Fu W, Zhang C, Xu D (2017) Isobavachalcone attenuates MPTP-induced Parkinson's disease in mice by inhibition of microglial activation through NF-κB pathway. PLoS ONE 12:e0169560PubMedPubMedCentral

Jurcovicova J (2014) Glucose transport in brain—effect of inflammation. Endocr Regul 48:35–48PubMed

Kamat PK (2015) Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism. Neural Regen Res 10:1050–1052PubMedPubMedCentral

Kang L, Routh VH, Kuzhikandathil EV, Gaspers LD, Levin BE (2004) Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 53:549–559PubMed

Kaundal M, Deshmukh R, Akhtar M (2018) Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: possible neurotransmitters and neuroinflammatory mechanism. Pharmacol Rep 70:540–548PubMed

Kleinridders A, Cai W, Cappellucci L, Ghazarian A, Collins WR, Vienberg SG, Pothos EN, Kahn CR (2015) Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc Natl Acad Sci USA 11:3463–3468

Knezovic A, Osmanovic Barilar J, Babic A, Bagaric R, Farkas V, Riederer P, Salkovic-Petrisic M (2018) Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer's disease. Neuropharmacology 135:48–62PubMed

Knezovic A, Osmanovic-Barilar J, Curlin M, Hof PR, Simic G, Riederer P, Salkovic-Petrisic M (2015) Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer's disease. J Neural Transm (Vienna) 122:577–592

Knezovic A, Loncar A, Homolak J, Smailovic U, Osmanovic Barilar J, Ganoci L, Bozina N, Riederer P, Salkovic-Petrisic M (2017) Rat brain glucose transporter-2, insulin receptor and glial expression are acute targets of intracerebroventricular streptozotocin: risk factors for sporadic Alzheimer's disease? J Neural Transm (Vienna) 124:695–708

Ko WKD, Camus SM, Li Q, Yang J, McGuire S, Pioli EY, Bezard E (2016) An evaluation of istradefylline treatment on Parkinsonian motor and cognitive deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque models. Neuropharmacology 110:48–58PubMed

Kraska A, Santin MD, Dorieux O, Joseph-Mathurin N, Bourrin E, Petit F, Jan C, Chaigneau M, Hantraye P, Lestage P, Dhenain M (2012) In vivo cross-sectional characterization of cerebral alterations induced by intracerebroventricular administration of streptozotocin. PLoS ONE 7:e46196PubMedPubMedCentral

Krishnamoorthy A, Sevanan M, Mani S, Balu M, Balaji S, Ramajayan P (2019) Chrysin restores MPTP induced neuroinflammation, oxidative stress and neurotrophic factors in an acute Parkinson's disease mouse model. Neurosci Lett 709:134382PubMed

Kumar A, Singh N (2017) Inhibitor of phosphodiestearse-4 improves memory deficits, oxidative stress, neuroinflammation and neuropathological alterations in mouse models of dementia of Alzheimer's Type. Biomed Pharmacother 88:698–707PubMed

Kumar M, Bansal N (2018) Ellagic acid prevents dementia through modulation of PI3-kinase-endothelial nitric oxide synthase signalling in streptozotocin-treated rats. Naunyn Schmiedebergs Arch Pharmacol 391:987–1001PubMed

Lacković Z, Salković M (1990) Streptozotocin and alloxan produce alterations in rat brain monoamines independently of pancreatic beta cells destruction. Life Sci 46:49–54PubMed

Lagrue E, Abe H, Lavanya M, Touhami J, Bodard S, Chalon S, Battini JL, Sitbon M, Castelnau P (2010) Regional characterization of energy metabolism in the brain of normal and MPTP-intoxicated mice using new markers of glucose and phosphate transport. J Biomed Sci 17:91PubMedPubMedCentral

Lana E, Khanbolouki M, Degavre C, Samuelsson EB, Åkesson E, Winblad B, Alici E, Lithner CU, Behbahani H (2017) Perforin promotes amyloid beta internalisation in neurons. Mol Neurobiol 54:874–887PubMed

Landrigan PJ, Sonawane B, Butler RN, Trasande L, Callan R, Droller D (2005) Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 113:1230–1233PubMedPubMedCentral

Lau YS, Meredith GE (2003) From drugs of abuse to parkinsonism. The MPTP mouse model of Parkinson's disease. Methods Mol Med 79:103–116PubMed

Lee Y, Kim YH, Park SJ, Huh JW, Kim SH, Kim SU, Kim JS, Jeong KJ, Lee KM, Hong Y, Lee SR, Chang KT (2014) Insulin/IGF signaling-related gene expression in the brain of a sporadic Alzheimer's disease monkey model induced by intracerebroventricular injection of streptozotocin. J Alzheimers Dis. 38:251–267PubMed

Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM (2006) Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. J Alzheimers Dis 9:13–33PubMed

Levin J (2019) Parkinsonism in genetic and sporadic Alzheimer's disease. Int Rev Neurobiol 149:237–247PubMed

Liu AK, Chang RC, Pearce RK, Gentleman SM (2015) Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease. Acta Neuropathol 129:527–540PubMedPubMedCentral

Lim HS, Kim JS, Moon BC, Ryu SM, Lee J, Park G (2019) Batryticatus bombyx protects dopaminergic neurons against MPTP-induced neurotoxicity by inhibiting oxidative damage. Antioxidants (Basel) 8(12):E574

Liu Y, Liu F, Iqbal K, Grundke-Iqbal K, Gong CX (2008) Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 582:359–364PubMedPubMedCentral

Liu A, Zhao X, Li H, Liu Z, Liu B, Mao X, Guo L, Bi K, Jia Y (2014) 5-Hydroxymethylfurfural, an antioxidant agent from Alpinia oxyphylla Miq. improves cognitive impairment in Aβ 1–42 mouse model of Alzheimer's disease. Int Immunopharmacol 23:719–725PubMed

Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2009) Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer disease. J Neurochem 111:242–249PubMedPubMedCentral

Liu Y, Geng L, Zhang J, Wang J, Zhang Q, Duan D, Zhang Q (2018) Oligo-porphyran ameliorates neurobehavioral deficits in parkinsonian mice by regulating the PI3K/Akt/Bcl-2 pathway. Mar Drugs 16:3

Ma D, Shuler JM, Raider KD, Rogers RS, Wheatley JL, Geiger PC, Stanford JA (2015) Effects of discontinuing a high-fat diet on mitochondrial proteins and 6-hydroxydopamine-induced dopamine depletion in rats. Brain Res 1613:49–58PubMedPubMedCentral

Ma Y, Zhan M, OuYang L, Li Y, Chen S, Wu J, Chen J, Luo C, Lei W (2014) The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats. Behav Brain Res 266:37–45PubMed

Maione F, Piccolo M, De Vita S, Chini MG, Cristiano C, De Caro C, Lippiello P, Miniaci MC, Santamaria R, Irace C, De Feo V, Calignano A, Mascolo N, Bifulco G (2017) Down regulation of pro-inflammatory pathways by tanshinone IIA and cryptotanshinone in a non-genetic mouse model of Alzheimer's disease. Pharmacol Res 129:482–490PubMed

Majkutewicz I, Kurowska E, Podlacha M, Myślińska D, Grembecka B, Ruciński J, Plucińska K, Jerzemowska G, Wrona D (2016) Dimethyl fumarate attenuates intracerebroventricular streptozotocin-induced spatial memory impairment and hippocampal neurodegeneration in rats. Behav Brain Res 308:24–37PubMed

Mansur RB, Lee Y, Subramaniapillai M, Cha DS, Brietzke E, McIntyre RS (2019) Parsing metabolic heterogeneity in mood disorders: a hypothesis-driven cluster analysis of glucose and insulin abnormalities. Bipolar Disord. https://doi.org/10.1111/bdi.12826(epub ahead of print) CrossRefPubMed

Mantych GJ, James DE, Chung HD, Devaskar SU (1992) Cellular localization and characterization of Glut 3 glucose transporter isoform in human brain. Endocrinology 131:1270–1278PubMed

Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689PubMed

Martinez A, Perez DI, Gil C (2013) Lessons learnt from glycogen synthase kinase 3 inhibitors development for Alzheimer's disease. Curr Top Med Chem 13:1808–1819PubMed

Mori MA, Delattre AM, Carabelli B et al (2018) Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson's disease is mediated by a reduction of inducible nitric oxide synthase. Nutr Neurosci. 21:341–351PubMed

Moriguchi S, Yabuki Y, Fukunaga K (2012) Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice. J Neurochem 120:541–551PubMed

Morris JK, Zhang H, Gupte AA, Bomhoff GL, Stanford JA, Geiger PC (2008) Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinson's disease. Brain Res. 1240:185–195PubMedPubMedCentral

Morroni F, Sita G, Tarozzi A, Rimondini R, Hrelia P (2016) Early effects of Aβ1-42 oligomers injection in mice: involvement of PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways. Behav Brain Res 314:106–115PubMed

Motzko-Soares ACP, Vizin RCL, Martins TMS, Hungaro ARO, Sato JR, Almeida MC, Carrettiero DC (2018) Thermoregulatory profile of neurodegeneration-induced dementia of the Alzheimer's type using intracerebroventricular streptozotocin in rats. Acta Physiol (Oxf) 224:e13084

Mukhin VN, Sizov VV, Pavlov KI, Klimenko VM (2019) β-Amyloid 25–35 suppresses the secretory activity of the dopaminergic system in the rat brain. Neurosci Behav Physiol 49:816–821

Narayan P, Holmström KM, Kim DH, Whitcomb DJ, Wilson MR, St George-Hyslop P, Wood NW, Dobson CM, Cho K, Abramov AY, Klenerman D (2014) Rare individual amyloid-β oligomers act on astrocytes to initiate neuronal damage. Biochemistry 53:2442–2453PubMedPubMedCentral

Nassar SZ, Badae NM, Issa YA (2018) Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer's disease. Arch Physiol Biochem 17:1–9

Nezhadi A, Sheibani V, Esmaeilpour K, Shabani M, Esmaeili-Mahani S (2016) Neurosteroid allopregnanolone attenuates cognitive dysfunctions in 6-OHDA-induced rat model of Parkinson's disease. Behav Brain Res 305:258–264PubMed

O'Keeffe ST, Kazeem H, Philpott RM, Playfer JR, Gosney M, Lye M (1996) Gait disturbance in Alzheimer's disease: a clinical study. Age Ageing 25:313–316PubMed

Osmanovic J, Plaschke K, Salkovic-Petrisic M, Grünblatt E, Riederer P, Hoyer S (2010) Chronic exogenous corticosterone administration generates an insulin-resistant brain state in rats. Stress 13:123–131PubMed

Ozkay UD, Can OD, Ozkay Y, Oztürk Y (2012) Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits. Pharmacol Rep 64:834–847PubMed

Pandey D, Banerjee S, Basu M, Mishra N (2016) Memory enhancement by Tamoxifen on amyloidosis mouse model. Horm Behav 79:70–73PubMed

Pearson-Leary J, McNay EC (2012a) Intrahippocampal administration of amyloid-β(1–42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism. J Alzheimers Dis 30:413–422PubMedPubMedCentral

Pellegrini C, Fornai M, Colucci R, Tirotta E, Blandini F, Levandis G, Cerri S, Segnani C, Ippolito C, Bernardini N, Cseri K, Blandizzi C, Haskó G, Antonioli L (2016) Alteration of colonic excitatory tachykininergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration. J Neuroinflamm 13:146

Peng S, Ma Y, Flores J, Cornfeldt M, Mitrovic B, Eidelberg D, Doudet JD (2016b) Modulation of abnormal metabolic brain networks by experimental therapies in a nonhuman primate model of parkinson disease: an application to human retinal pigment epithelial cell implantation. J Nucl Med 57:1591–1598PubMedPubMedCentral

Pérez V, Marin C, Rubio A, Aguilar E, Barbanoj M, Kulisevsky J (2009) Effect of the additional noradrenergic neurodegeneration to 6-OHDA-lesioned rats in levodopa-induced dyskinesias and in cognitive disturbances. J Neural Transm (Vienna) 116:1257–1266

Pinessi L, Rainero I, De Gennaro T, Gentile S, Portaleone P, Bergamasco B (1987) Biogenic amines in cerebrospinal fluid and plasma of patients with dementia of Alzheimer type. Funct Neurol 2:51–58PubMed

Pizzolato G, Chierichetti F, Fabbri M, Cagnin A, Dam M, Ferlin G, Battistin L (1996) Reduced striatal dopamine receptors in Alzheimer's disease: single photon emission tomography study with the D2 tracer [123I]-IBZM. Neurology 47:1065–1068PubMed

Plum L, Schubert M, Brüning JC (2005) The role of insulin receptor signaling in the brain. Trends Endocrinol Metab 16:59–65PubMed

Prediger RD, Batista LC, Medeiros R, Pandolfo P, Florio JC, Takahashi RN (2006) The risk is in the air: intranasal administration of MPTP to rats reproducing clinical features of Parkinson's disease. Exp Neurol 202:391–403PubMed

Przedborski S, Jackson-Lewis V, Djaldetti R, Liberatore G, Vila M, Vukosavic S, Almer G (2000) The parkinsonian toxin MPTP: action and mechanism. Restor Neurol Neurosci 16:135–142PubMed

Puchades M, Sogn CJ, Maehlen J, Bergersen LH, Gundersen V (2013) Unaltered lactate and glucose transporter levels in the MPTP mouse model of Parkinson's disease. J Parkinsons Dis 3:371–385PubMed

Rabie MA, Abd El Fattah MA, Nassar NN, El-Abhar HS, Abdallah DM (2018) Angiotensin 1–7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis. Biochem Pharmacol 151:126–134PubMed

Rai SN, Dilnashin H, Birla H, Singh SS, Zahra W, Rathore AS, Singh BK, Singh SP (2019) The role of PI3K/Akt and ERK in neurodegenerative disorders. Neurotox Res 35:775–795PubMed

Rajasekar N, Dwivedi S, Nath C, Hanif K, Shukla R (2014) Protection of streptozotocin induced insulin receptor dysfunction, neuroinflammation and amyloidogenesis in astrocytes by insulin. Neuropharmacology 86:337–352PubMed

Ramírez-García G, Palafox-Sánchez V, Limón ID (2015) Nitrosative and cognitive effects of chronic L-DOPA administration in rats with intra-nigral 6-OHDA lesion. Neuroscience 290:492–508PubMed

Razavinasab M, Shamsizadeh A, Shabani M, Nazeri M, Allahtavakoli M, Asadi-Shekaari M, Esmaeli-Mahani S, Sheibani V (2013) Pharmacological blockade of TRPV1 receptors modulates the effects of 6-OHDA on motor and cognitive functions in a rat model of Parkinson's disease. Fundam Clin Pharmacol 27:632–640PubMed

Riederer P, Berg D, Casadei N, Cheng F, Classen J, Dresel C et al (2019) α-Synuclein in Parkinson's disease: causal or bystander? J Neural Transm (Vienna) 126:815–840

Rodrigues L, Wartchow KM, Suardi LZ, Federhen BC, Selistre NG, Gonçalves CA (2019) Streptozotocin causes acute responses on hippocampal S100B and BDNF proteins linked to glucose metabolism alterations. Neurochem Int 128:85–93PubMed

Russo I, Caracciolo L, Tweedie D, Choi SH, Greig NH, Barlati S, Bosetti F (2012) 3,6'-Dithiothalidomide, a new TNF-α synthesis inhibitor, attenuates the effect of Aβ1–42 intracerebroventricular injection on hippocampal neurogenesis and memory deficit. J Neurochem 122:1181–1192PubMedPubMedCentral

Saab AS, Neumeyer A, Jahn HM, Cupido A, Šimek AA, Boele HJ, Scheller A, Le Meur K, Götz M, Monyer H, Sprengel R, Rubio ME, Deitmer JW, De Zeeuw CI, Kirchhoff F (2012) Bergmann glial AMPA receptors are required for fine motor coordination. Science 337:749–753PubMed

Salković M, Sabolić I, Lacković Z (1995) Striatal dopaminergic D1 and D2 receptors after intracerebroventricular application of alloxan and streptozocin in rat. J Neural Transm Gen Sect 100:137–145PubMed

Salkovic-Petrisic M, Tribl F, Schmidt M, Hoyer S, Riederer P (2006) Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway. J Neurochem 96:1005–1015PubMed

Salkovic-Petrisic M, Osmanovic J, Grünblatt E, Riederer P, Hoyer S (2009) Modeling sporadic Alzheimer's disease: the insulin resistant brain state generates multiple long-term morphobiological abnormalities including hyperphosphorylated tau protein and amyloid-beta. J Alzheimers Dis 18:729–750PubMed

Salkovic-Petrisic M, Osmanovic-Barilar J, Knezovic A, Hoyer S, Mosetter K, Reutter W (2014) Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin. Neuropharmacology 77:68–80PubMed

Salković-Petrisić M, Lacković Z (2003) Intracerebroventricular administration of betacytotoxics alters expression of brain monoamine transporter genes. J Neural Transm (Vienna) 110:15–29

Sandyk R, Iacono RP, Kay SR (1990) The hypothalamus in MPTP-induced Parkinsonism. Ital J Neurol Sci 20:20

Santiago JA, Potashkin JA (2013) Shared dysregulated pathways lead to Parkinson's disease and diabetes. Trends Mol Med 11(4):367–372

Sarkar S, Chigurupati S, Raymick J, Mann D, Bowyer JF, Schmitt T, Beger RD, Hanig JP, Schmued LC, Paule MG (2014) Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP-induced Parkinson's disease mouse model. Neurotoxicology 44:250–262PubMed

Schechter R, Holtzclaw L, Sadiq F, Kahn A, Devaskar S (1988) Insulin synthesis by isolated rabbit neurons. Endocrinology 123:505–513PubMed

Schelp AO, Mendes-Chiloff CL, Paduan VC, Corrente JE, Vieira A, Marchette JCN, de Souza JT, Luvizuto GJ, Nogueira CR, Bazan R (2017) Amnestic dementia impairment in Parkinson's disease: the role of body composition, ageing and insulin resistance. Clin Nutr ESPEN 20:47–51PubMed

Schmid S, Jungwirth B, Gehlert V, Blobner M, Schneider G, Kratzer S, Kellermann K, Rammes G (2017) Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test. Behav Brain Res 324:15–20PubMed

Schnedl WJ, Ferber S, Johnson JH, Newgard CB (1994) STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes 43:1326–1333PubMed

Schulingkamp RJ, Pagano TC, Hung D, Raffa RB (2000) Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 24:855–872PubMed

Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V (2012) Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 33:430.e5–18

Shyu WC, Li KW, Peng HF, Lin SZ, Liu RS, Wang HJ, Su CY, Lee YJ, Li H (2009) Induction of GAP-43 modulates neuroplasticity in PBSC (CD34+) implanted-Parkinson's model. J Neurosci Res 87:2020–2033PubMed

Silva MD, Glaus C, Hesterman JY, Hoppin J, Puppa GH, Kazules T, Orcutt KM, Germino M, Immke D, Miller S (2013) Regional, kinetic [(18)F]FDG PET imaging of a unilateral Parkinsonian animal model. Am J Nucl Med Mol Imaging 3:129–141PubMedPubMedCentral

Simpson IA, Dwyer D, Malide D, Moley KH, Travis A, Vannucci SJ (2008) The facilitative glucose transporter GLUT3: 20 years of distinction. Am J Physiol Endocrinol Metab 295:E242–253PubMedPubMedCentral

Singh S, Kumar P (2017) Neuroprotective potential of curcumin in combination with piperine against 6-hydroxy dopamine induced motor deficit and neurochemical alterations in rats. Inflammopharmacology 25:69–79PubMed

Solesio MA, Prime TA, Logan A, Murphy MP, Arroyo-Jimenez MM, Jordán J, Galindo MF (2013) The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease. BBA Mol Basis Disease 1832:174–182

Sriram K, Pai KS, Boyd MR, Ravindranath V (1997) Evidence for generation of oxidative stress in brain by MPTP: in vitro and in vivo studies in mice. Brain Res 749:44–52PubMed

Storch A, Ludolph AC, Schwarz J (2004) Dopamine transporter: involvement in selective dopaminergic neurotoxicity and degeneration. J Neural Transm 111:1267–1286PubMed

Storga D, Vrecko K, Birkmayer JG, Reibnegger G (1996) Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients. Neurosci Lett 203:29–32PubMed

Stouffer MA, Woods CA, Patel JC, Lee CR, Witkovsky P, Bao L, Machold RP, Jones KT, de Vaca SC, Reith ME, Carr KD, Rice ME (2015) Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward. Nat Commun 6:8543PubMedPubMedCentral

Sun P, Ortega G, Tan Y, Hua Q, Riederer PF, Deckert J, Schmitt-Böhrer AG (2018) Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system. Front Aging Neurosci 10:145PubMedPubMedCentral

Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:537–546PubMed

Tanji H, Araki T, Nagasawa H, Itoyama Y (1999) Differential vulnerability of dopamine receptors in the mouse brain treated with MPTP. Brain Res 824:224–231PubMed

Thornton E, Vink R (2012) Treatment with a substance P receptor antagonist is neuroprotective in the intrastriatal 6-hydroxydopamine model of early Parkinson's disease. PLoS ONE 7:e34138PubMedPubMedCentral

Tieu K (2011) A guide to neurotoxic animal models of Parkinson's disease. Cold Spring Harb Perspect Med 1:a009316PubMedPubMedCentral

Tong M, Neusner A, Longato L, Lawton M, Wands JR, de la Monte SM (2009) Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer's disease. J Alzheimers Dis 17:827–844PubMedPubMedCentral

Trabace L, Kendrick KM, Castrignanò S, Colaianna M, De Giorgi A, Schiavone S, Lanni C, Cuomo V, Govoni S (2007) Soluble amyloid beta1-42 reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide. Neuroscience 147:652–663PubMed

Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM (2013) ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proc Natl Acad Sci USA 110:E1807–1816PubMed

Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E (2011) Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson's disease. PLoS ONE 6:e23952PubMedPubMedCentral

Vučković MG, Li Q, Fisher B, Nacca A, Leahy RM, Walsh JP, Mukherjee J, Williams C, Jakowec MW, Petzinger GME (2010) Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: in vivo imaging with [¹⁸F]fallypride. Mov Disord 25:2777–2784PubMedPubMedCentral

Walsh S, Finn DP, Dowd E (2011) Time-course of nigrostriatal neurodegeneration and neuroinflammation in the 6-hydroxydopamine induced axonal and terminal lesion models of Parkinson's disease in the rat. Neuroscience 175:251–261PubMed

Wang C, Cai Z, Wang W, Wei M, Kou D, Li T, Yang Z, Guo H, Le W, Li S (2019) Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer's disease. J Nutr Biochem 70:147–155PubMed

Wang D, Liu L, Li S, Wang C (2018a) Effects of paeoniflorin on neurobehavior, oxidative stress, brain insulin signaling, and synaptic alterations in intracerebroventricular streptozotocin-induced cognitive impairment in mice. Physiol Behav 191:12–20PubMed

Wang H, Wang R, Zhao Z, Ji Z, Xu S, Holscher C (2009) Coexistences of insulin signaling-related proteins and choline acetyltransferase in neurons. Brain Res 1249:237–243PubMed

Wang Y, Yu X, Zhang P, Ma Y, Wang L, Xu H, Sui D (2018b) Neuroprotective effects of pramipexole transdermal patch in the MPTP-induced mouse model of Parkinson's disease. J Pharmacol Sci 138:31–37PubMed

Wei J, Yang F, Gong C, Shi X, Wang G (2019) Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model. J Biochem Mol Toxicol 21:e22319

Weihmuller FB, Bruno JP, Neff NH, Hadjiconstantinou M (1990) Dopamine receptor plasticity following MPTP-induced nigrostriatal lesions in the mouse. Eur J Pharmacol 1180:369–372

Wesén E, Jeffries GDM, Matson Dzebo M, Esbjörner EK (2017) Endocytic uptake of monomeric amyloid-β peptides is clathrin- and dynamin-independent and results in selective accumulation of Aβ(1–42) compared to Aβ(1–40). Sci Rep 7:2021PubMedPubMedCentral

Wilcox BJ, Matsumoto AM, Dorsa DM, Baskin DG (1989) Reduction of insulin binding in the arcuate nucleus of the rat hypothalamus after 6-hydroxydopamine treatment. Brain Res 500:149–155PubMed

Woiciechowsky C, Guilarte TR, May CH, Vesper J, Wagner HN Jr, Vogel S (1995) Intrastriatal dopamine infusion reverses compensatory increases in D2-dopamine receptors in the 6-OHDA lesioned rat. Neurodegeneration 4:161–169PubMed

Wu KL, Hung CY, Chan JY, Wu CW (2014) An increase in adenosine-5'-triphosphate (ATP) content in rostral ventrolateral medulla is engaged in the high fructose diet-induced hypertension. J Biomed Sci 27:21–28

Wu Y, Shang Y, Sun S, Liang H, Liu R (2007) Erythropoietin prevents PC12 cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis via the Akt/GSK-3beta/caspase-3 mediated signaling pathway. Apoptosis 12:1365–1375PubMed

Xu L, Sapolsky RM, Giffard RG (2001) Differential sensitivity of murine astrocytes and neurons from different brain regions to injury. Exp Neurol 169:416–424PubMed

Xu M, Zhang HL (2011) Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. Acta Pharmacol Sin 32:1089–1099PubMedPubMedCentral

Xu M, Dong Y, Wan S, Yan T, Cao J, Wu L, Bi K, Jia Y (2016) Schisantherin B ameliorates Aβ1-42-induced cognitive decline via restoration of GLT-1 in a mouse model of Alzheimer's disease. Physiol Behav 167:265–273PubMed

Yabuki Y, Ohizumi Y, Yokosuka A, Mimaki Y, Fukunaga K (2014) Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice. Neuroscience 259:126–141PubMed

Yan JJ, Kim DH, Moon YS, Jung JS, Ahn EM, Baek NI, Song DK (2004) Protection against beta-amyloid peptide-induced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. Prog Neuropsychopharmacol Biol Psychiatry 28:25–30PubMed

Yang JS, Wu XH, Yu HG, Teng LS (2017) Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats. Inflammopharmacology 25:471–484PubMed

Yang L, Wang H, Liu L, Xie A (2018) The role of insulin/IGF-1/PI3K/Akt/GSK3β signaling in Parkinson's disease dementia. Front Neurosci 12:73PubMedPubMedCentral

Yin F, Sancheti H, Patil I, Cadenas E (2016) Energy metabolism and inflammation in brain aging and Alzheimer's disease. Free Radic Biol Med 100:108–122PubMedPubMedCentral

Zhang H, Wang D, Gong P, Lin A, Zhang Y, Ye RD, Yu Y (2019a) Formyl peptide receptor 2 deficiency improves cocgnition and attenuates tau hyperphosphorylation and astrogliosis in a mouse model of Alzheimer's disease. J Alzheimers Dis 67:169–179PubMed

Zhang L, Zhang L, Li L, Hölscher C (2019b) Semaglutide is neuroprotective and reduces α-synuclein levels in the chronic MPTP mouse model of Parkinson's disease. J Parkinsons Dis 9:157–171PubMed

Zhao C, Ling Z, Newman MB, Bhatia A, Carvey PM (2007) TNF-alpha knockout and minocycline treatment attenuates blood–brain barrier leakage in MPTP-treated mice. Neurobiol Dis 26:36–46PubMedPubMedCentral

Zhu J, Gao W, Shan X, Wang C, Wang H, Shao Z, Dou S, Jiang Y, Wang C, Cheng B (2019) Apelin-36 mediates neuroprotective effects by regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson's disease model mice. Brain Res 1726:146493PubMed

Zussy C, Brureau A, Delair B, Marchal S, Keller E, Ixart G, Naert G, Meunier J, Chevallier N, Maurice T, Givalois L (2011) Time-course and regional analyses of the physiopathological changes induced after cerebral injection of an amyloid β fragment in rats. Am J Pathol 179:315–334PubMedPubMedCentral

Title: Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease
Authors: Jelena Osmanovic Barilar
Ana Knezovic
Ana Babic Perhoc
Jan Homolak
Peter Riederer
Melita Salkovic-Petrisic
Publication date: 01-02-2020
Publisher: Springer Vienna
Keywords: Insulins
Alzheimer's Disease
Alzheimer's Disease
Pathology
Parkinson's Disease
Insulins
Published in: Journal of Neural Transmission / Issue 2/2020
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-020-02152-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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