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01-01-2015 | Original Article

An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease

Authors: Ilse S. Pienaar, Ian F. Harrison, Joanna L. Elson, Alexander Bury, Petter Woll, Anna Katharina Simon, David T. Dexter

Published in: Brain Structure and Function | Issue 1/2015

Abstract

A rostral brainstem structure, the pedunculopontine nucleus (PPN), is severely affected by Parkinson’s disease (PD) pathology and is regarded a promising target for therapeutic deep-brain stimulation (DBS). However, understanding the PPN’s role in PD and assessing the potential of DBS are hampered by the lack of a suitable model of PPN degeneration. Rats were rendered Parkinsonian through a unilateral substantia nigra pars compacta (SNpc) stereotaxic injection of the proteasome inhibitor Lactacystin, to investigate whether the lesion’s pathological effects spread to impact the integrity of PPN cholinergic neurons which are affected in PD. At 5 weeks post-surgery, stereological analysis revealed that the lesion caused a 48 % loss of dopaminergic SNpc neurons and a 61 % loss of PPN cholinergic neurons, accompanied by substantial somatic hypotrophy in the remaining cholinergic neurons. Magnetic resonance imaging revealed T2 signal hyper-/hypointensity in the PPN of the injected hemisphere, respectively at weeks 3 and 5 post-lesion. Moreover, isolated PPN cholinergic neurons revealed no significant alterations in key autophagy mRNA levels, suggesting that autophagy-related mechanisms fail to protect the PPN against Lactacystin-induced cellular changes. Hence, the current results suggest that the Lactacystin PD model offers a suitable model for investigating the role of the PPN in PD.

Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69:1326–1329. doi:10.1046/j.1471-4159.1997.69031326.x PubMedCrossRef

Alessandro S, Ceravolo R, Brusa L, Pierantozzi M, Costa A, Galati S, Placidi F, Romigi A et al (2010) Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: focus on sleep and cognitive domains. J Neurol Sci 289:44–48. doi:10.1016/j.jns.2009.08.017 PubMedCrossRef

Antonini A, Leenders KL, Meier D, Oertel WH, Boesiger P, Anliker M (1993) T2 relaxation time in patients with Parkinson’s disease. Neurology 43:697. doi:10.1212/WNL.43.4.697 PubMedCrossRef

Bandhyopadhyay U, Cuervo AM (2007) Chaperone-mediated autophagy in aging and neurodegeneration: lessons from alpha-synuclein. Exp Gerontol 42:120–128. doi:10.1016/j.exger.2006.05.019

Baquet ZC, Williams D, Brody J, Smeyne RJ (2009) A comparison of modelbased (2D) and design-based (3D) stereological methods for estimating cell number in the substantia nigra pars compacta (SNpc) of the C57BL/6J mouse. Neuroscience 161:1082–1090. doi:10.1016/j.neuroscience.2009.04.031 PubMedCentralPubMedCrossRef

Baskerville KA, Kent C, Personett D, Lai WR, Park PJ, Coleman P, Mckinney M (2008) Aging elevates metabolic gene expression in brain cholinergic neurons. Neurobiol Aging 29:1874–1893. doi:10.1016/j.neurobiolaging.2007.04.024 PubMedCrossRef

Bohnen NI, Albin RL (2011) The cholinergic system and Parkinson disease. Behav Brain Res 221:564–573. doi:10.1016/j.bbr.2009.12.048 PubMedCentralPubMedCrossRef

Brar S, Henderson D, Schenck J, Zimmerman E (2009) Iron accumulation in the substantia nigra of patients with Alzheimer disease and parkinsonism. Arch Neurol 66:371–374. doi:10.1001/archneurol.2008.586 PubMed

Bursch W (2001) The autophagosomal–lysosomal compartment in programmed cell death. Cell Death Differ 8:569–581. doi:10.1038/sj.cdd.4400852 PubMedCrossRef

Butler D, Nixon RA, Bahr BA (2006) Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases. Autophagy 2:234–237

Chen J, Hardy P, Kucharczyk W, Clauberg M, Joshi J, Vourlas A, Dhar M, Henkelman RM (1993) MR of human postmortem brain tissue: correlative study between T2 and assays of iron and ferritin in Parkinson and Huntington disease. AJNR Am J Neuroradiol 14:275–281PubMed

Cho BP, Song DY, Sugama S, Shin DH, Shimizu Y, Kim SS, Kim YS, Joh TH (2006) Pathological dynamic of activated microglia following medial forebrain bundle transection. Glia 53:92–102. doi:10.1002/glia.20265 PubMedCrossRef

Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–86. doi:10.1038/nrm1552 PubMedCrossRef

Cook C, Petrucelli L (2009) A critical evaluation of the ubiquitin proteasome system in Parkinson’s disease. Biochim Biophys Acta 1792:664–675. doi:10.1016/j.bbadis.2009.01.012 PubMedCentralPubMedCrossRef

Dexter DT, Wells FR, Lee AJ, Agid F, Agid Y, Jenner P, Marsden CD (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52:1830–1836. doi:10.1111/j.1471-4159.1989.tb07264.x PubMedCrossRef

Dickson DW (2007) Linking selective vulnerability to cell death mechanisms in Parkinson’s disease. Am J Pathol 170:16–19. doi:10.2353/ajpath.2007.061011 PubMedCentralPubMedCrossRef

Dugger BN, Murray ME, Boeve BF, Parisi JE, Benarroch EE, Ferman TJ, Dickson DW (2012) Neuropathological analysis of brainstem cholinergic and catecholaminergic nuclei in relation to REM sleep behaviour disorder. Neuropathol Appl Neurobiol 38:142–152. doi:10.1111/j.1365-2990.2011.01203 PubMedCentralPubMedCrossRef

Ferraye MU, Debû B, Fraix V, Goetz L, Ardouin C, Yelnik J, Henry-Lagrange C, Seigneuret E et al (2010) Effects of pedunculopontine nucleus area stimulation on gait disorders in Parkinson’s disease. Brain 133:205–214. doi:10.1093/brain/awp229 PubMedCrossRef

Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K et al (2002) α-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164. doi:10.1038/ncb748 PubMedCrossRef

Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM (2000) Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 290:985–989. doi:10.1126/science.290.5493.985 PubMedCrossRef

Gorell JM, Ordidge RJ, Brown GG, Deniau J-C, Buderer NM, Helpern JA (1995) Increased iron-related MRI contrast in the substantia nigra in Parkinson’s disease. Neurology 45:1138–1143. doi:10.1212/WNL.45.6.1138 PubMedCrossRef

Gundersen HJG (1977) Notes on the estimation of the numerical density of arbitrary particles. J Microsc 111:219–223CrossRef

Halliday GM (2009) Thalamic changes in Parkinson’s disease. Parkinsonism Relat Disord 15:S152–S155. doi:10.1016/S1353-8020(09)70804-1 PubMedCrossRef

Healy-Stoffel M, Ahmad SO, Stanford JA, Levant B (2012) A novel use of combined tyrosine hydroxylase and silver nucleolar staining to determine the effects of a unilateral intrastriatal 6-hydroxydopamine lesion in the substantia nigra: a stereological study. J Neurosci Methods 2010:187–194. doi:10.1016/j.jneumeth.2012.07.013 CrossRef

Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976–5980PubMedCentralPubMedCrossRef

Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoiola F, Tolosa E (2006) Rapid-eye movement sleep behaviour disorder as an early marker for neurodegenerative disorder: a descriptive study. Lancet Neurol 5:572–577. doi:10.1016/S1474-4422(06)70476-8 PubMedCrossRef

Jenkinson N, Nandi D, Miall RC, Stein JF, Aziz TZ (2004) Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey. NeuroReport 15:2621–2624PubMedCrossRef

Jenkinson N, Nandi D, Oram R, Stein JF, Aziz TZ (2006) Pedunculopontine nucleus electric stimulation alleviates akinesia independently of dopaminergic mechanisms. NeuroReport 17:639–641PubMedCrossRef

Karachi C, Grabli D, Bernard FA, Tandé D, Wattiez N, Belaid H, Bardinet E, Prigent A et al (2010) Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease. J Clin Invest 120:1026–1033. doi:10.1172/JCI42642 CrossRef

Kaur C, Ling EA (1992) Activation and re-expression of surface antigen in microglia following an epidural application of kainic acid in the rat brain. J Anat 180:333–342PubMedCentralPubMed

Kondoh T, Bannai M, Nishino H, Torii K (2005) 6-Hydroxydopamine induced lesions in a rat model of hemi-Parkinson’s disease monitored by magnetic resonance imaging. Exp Neurol 192:194–202. doi:10.1016/j.expneurol.2004.12.016 PubMedCrossRef

Kosta P, Argyropoulou M, Markoula S, Konitsiotis S (2006) MRI evaluation of the basal ganglia size and iron content in patients with Parkinson’s disease. J Neurol 253:26–32. doi:10.1007/s00415-005-0914-9 PubMedCrossRef

Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318PubMedCrossRef

Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol 75:345–353PubMedCrossRef

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408. doi:10.1006/meth 2001.1262PubMedCrossRef

Lorenc-Koci E, Lenda T, Antkiewicz-Michaluk L, Wardas J, Domin H, Smiałowska M, Konieczny J (2011) Different effects of intranigral and intrastriatal administration of the proteasome inhibitor lactacystin on typical neurochemical and histological markers of Parkinson’s disease in rats. Neurochem Internat 58:839–849. doi:10.1016/j.neuint.2011.03.013 CrossRef

Lue L-F, Kuo Y-M, Beach T, Walker DG (2010) Microglia activation and anti-inflammatory regulation in Alzheimer’s disease. Mol Neurobiol 41:115–128. doi:10.1007/s12035-010-8106-8 PubMedCentralPubMedCrossRef

MacInnes N, Iravani MM, Perry E, Piggott M, Perry R, Jenner P, Ballard C (2008) Proteasomal abnormalities in cortical Lewy body disease and the impact of proteasomal inhibition within cortical and cholinergic systems. J Neural Transm 115:869–878. doi:10.1007/s00702-008-0027-6 PubMedCrossRef

Mackey S, Jing Y, Flores J, Dinelle K, Doudet DJ (2013) Direct intranigral administration of an ubiquitin proteasome system inhibitor in rat: behaviour, positron emission tomography, immunohistochemistry. Exp Neurol 247:19–24. doi:10.1016/j.expneurol.2013.03.021 PubMedCrossRef

Maeno E, Ishizaki Y, Kanaseki T, Hazama A, Okada Y (2000) Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci USA 97:9487–9492. doi:10.1073/pnas.140216197 PubMedCentralPubMedCrossRef

Marinova-Mutafchieva L, Sadeghian M, Broom L, Davis JB, Medhurst AD, Dexter DT (2009) Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: a time course study in a 6-hydroxydopamine model of Parkinson’s disease. J Neurochem 110:966–975. doi:10.1111/j.1471-4159.2009.06189.x PubMedCrossRef

Martinez-Vicente M, Cuervo AM (2007) Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol 6:352–361. doi:10.1016/S1474-4422(07)70076-5 PubMedCrossRef

Maskos U (2008) The cholinergic mesopontine tegmentum is a relatively neglected nicotinic master modulator of the dopaminergic system: relevance to drugs of abuse and pathology. Br J Pharmacol 153:S438–S445. doi:10.1038/bjp.2008.5 PubMedCentralPubMedCrossRef

McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302–330. doi:10.1016/j.sleep.2007.03.005 PubMedCrossRef

McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P (2001) Failure of the ubiquitin–proteasome system in Parkinson’s disease. Nat Rev Neurosci 2:589–594. doi:10.1038/35086067 PubMedCrossRef

McNaught KSP, Mytilineou C, Jnobaptiste R, Yabut J, Shashidharan P, Jennert P, Oleo CW (2002) Impairment of the ubiquitin–proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J Neurochem 81:301–306. doi:10.1046/j.1471-4159.2002.00821.x PubMedCrossRef

Mena-Segovia J, Micklem BR, Nair-Roberts RG, Ungless MA, Bolam JP (2009) GABAergic neuron distribution in the pedunculopontine nucleus defines functional subterritories. J Comp Neurol 515:397–408. doi:10.1002/cne.22065 PubMedCrossRef

Menke RA, Scholz J, Miller KL, Deoni S, Jbabdi S, Matthews PM, Zarei M (2009) MRI characteristics of the substantia nigra in Parkinson’s disease: a combined quantitative T1 and DTI study. NeuroImage 47:435–441. doi:10.1016/j.neuroimage.2009.05.017 PubMedCrossRef

Mesulam MM, Mufson EJ, Wainer BH, Levey AI (1983) Central cholinergic pathways in the rat: an overview based on alternative nomenclature (Hh1-Ch6). Neuroscience 10:1185–1201PubMedCrossRef

Miletich RS, Bankiewicz KS, Quarantelli M, Plunkett RJ, Frank J, Kopin IJ, Di Chiro G (1994) MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys. Ann Neurol 35:689–697PubMedCrossRef

Moro E, Hamani C, Poon YY, Al-Khairallah T, Dostrovsky JO, Hutchison WD, Lozano AM (2010) Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain 133:215–224. doi:10.1093/brain/awp261 PubMedCrossRef

Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318. doi:10.1126/science.1110647 PubMedCrossRef

Niu C, Mei J, Pan Q, Fu X (2009) Nigral degeneration with inclusion body formation and behavioral changes in rats after proteasomal inhibition. Stereotact Funct Neurosurg 87:69–81. doi:10.1159/000202972 PubMedCentralPubMedCrossRef

Olanow CW, McNaught KS (2006) Ubiquitin-proteasome system and Parkinson’s disease. Mov Disord 21:1806–1823. doi:10.1002/mds.21013 PubMedCrossRef

Oorschot DE (1998) Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: a stereological study using the cavalieri and optical dissector methods. J Compar Neurol 366:580–599. doi:10.1002/(SICI)1096-9861(19960318 CrossRef

Ossig C, Reichmann H (2013) Treatment of Parkinson’s disease in the advanced stage. J Neural Transm. doi:10.1007/s00702-013-1008-y (in press)

Paine SML, Anderson G, Bedford K, Lawler K, Mayer RJ, Lowe J, Bedford L (2013) Pale body-like inclusion formation and neurodegeneration following depletion of 26S proteasomes in mouse brain neurones are independent of α-synuclein. PLoS One 8:e54711. doi:10.1371/journal.pone.0054711 PubMedCentralPubMedCrossRef

Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, San Diego

Paxinos G, Watson C (2009) The rat brain in stereotaxic coordinates. Academic Press, Sydney

Péran P, Nemmi F, Méligne D, Cardebat D, Peppe A, Rascol O, Caltagirone C, Demonet JF et al (2012) Effect of levodopa on both verbal and motor representations of action in Parkinson’s disease: a fMRI study. Brain Lang 125:324–329. doi:10.1016/j.bandl.2012.06.001 PubMedCrossRef

Petersen MA, Dailey ME (2004) Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices. Glia 46:195–206. doi:10.1002/glia.10362 PubMedCrossRef

Pienaar IS, Van de Berg W (2013) A non-cholinergic neuronal loss in the pedunculopontine nucleus of toxin-evoked Parkinsonian rats. Exp Neurol 248C:213–223. doi:10.1016/j.expneurol.2013.06.008 CrossRef

Pienaar IS, Kellaway LA, Russell VA, Stein DJ, Zigmond MJ, Daniels WMU (2007) Maternal separation exaggerates the toxic effects of 6-OHDA in adult rats: implications for neurodegenerative disorders. Stress 11:448–456. doi:10.1080/10253890801890721 CrossRef

Pienaar IS, Elson JL, Racca C, Nelson G, Turnbull DM, Morris CM (2013) Mitochondrial abnormality associates with type-specific neuronal loss and cell morphology changes in the pedunculopontine nucleus in Parkinson’s disease. Am J Pathol. pii:S0003-9440(13)00609-3 (in press)

Plaha P, Gill SS (2005) Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson’s disease. NeuroReport 16:1883–1887PubMedCrossRef

Platt B, Riedel G (2011) The cholinergic system, EEG and sleep. Behav Brain Res 221:299–504. doi:10.1016/j.bbr.2011.01.017 CrossRef

Rideout HJ, Larsen KE, Sulzer D, Stefanis L (2001) Proteasomal inhibition leads to formation of ubiquitin/alpha-synuclein-immunoreactive inclusions in PC12 cells. J Neurochem 78:899–908. doi:10.1046/j.1471-4159.2001.00474.x PubMedCrossRef

Rinne JO, Ma SY, Lee MS, Collan Y, Röyttä M (2008) Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson’s disease is related to disability of the patients. Parkinsonism Relat Disord 14:553–557. doi:10.1016/j.parkreldis.2008.01.006 PubMedCrossRef

Rochester L, Yarnall AJ, Baker MR, David RV, Lord S, Galna B, Burn DJ (2012) Cholinergic dysfunction contributes to gait disturbance in early Parkinson’s disease. Brain 135:2779–2788. doi:10.1093/brain/aws207 PubMedCentralPubMedCrossRef

Rodriguez-Pallares J, Parga JA, Munoz A, Rey P, Guerra MJ, Labandeira-Garcia JL (2007) Mechanism of 6-hydroxydopamine neurotoxicity: role of NADPH oxidase and microglial activation in 6-hydroxydopamine induced degeneration of dopaminergic neurons. J Neurochem 103:145–156. doi:10.1111/j.1471-4159.2007.04699.x PubMed

Rubinsztein DC (2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443:780–786. doi:10.1038/nature05291 PubMedCrossRef

Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST (2000) CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacol 39:777–787. doi:10.1016/s0028-3908(00)00005-8 CrossRef

Schenck CH, Bundie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38 % of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46:388–393. doi:10.1212/WNL.46.2.388 PubMedCrossRef

Schmitz C, Hof PR (2005) Design-based stereology in neuroscience. Neuroscience 130:813–831. doi:10.1016/j.neuroscience.2004.08.050 PubMedCrossRef

Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMedCrossRef

Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, Tropepi D, Pierantozzi M, Brusa L et al (2007) Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain 130:1596–15607. doi:10.1093/brain/awl346 PubMedCrossRef

Streit WJ, Kreutzberg GW (1988) Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin. J Comp Neurol 268:248–263PubMedCrossRef

Vernon AC, Johansson SM, Modo MM (2010) Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson’s disease. BMC Neurosci 11:1471–2202. doi:10.1186/1471-2202-11-1 CrossRef

Vernon AC, Crum WR, Johansson SM, Modo M (2011) Evolution of extra-nigral damage predicts behavioural deficits in a rat proteasome inhibitor model of Parkinson’s disease. PLoS One 6:e17269. doi:10.1371/journal.pone.0017269 PubMedCentralPubMedCrossRef

Vymazal J, Righini A, Brooks RA, Canesi M, Mariani C, Leonardi M, Pezzoli G (1999) T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 211:489–495PubMedCrossRef

Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974–3980. doi:10.1523/JNEUROSCI.4363-08.2009 PubMedCrossRef

West MJ (1993) New stereological methods for counting neurons. Neurobiol Aging 14:275–285PubMedCrossRef

West MJ, Gundersen HJ (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296:1–22PubMedCrossRef

Wolf OT, Dyakin V, Vadasz C, de Leon MJ, McEwen BS, Bulloch K (2002) Volumetric measurement of the hippocampus, the anterior cingulate cortex, and the retrosplenial granular cortex of the rat using structural MRI. Brain Res Brain Res Protoc 10:41–46. doi:10.1016/S1385-299X(02)00181-2 PubMedCrossRef

Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13:805–811. doi:10.1038/nn.2575 PubMedCentralPubMedCrossRef

Wu H, Malhotra K, Lalwani K, Li R, Cooc J, Danenberg KD, Williams M (2006) Multiplex qRT-PCR gene expression assay on the COBAS^® TaqMan 48 Analyzer using RNA extracted from formalin-fixed paraffin embedded tissue. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12–15. Abstract number: A11

Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306PubMedCrossRef

Yarnall A, Rochester L, Burn DJ (2011) The interplay of cholinergic function, attention, and falls in Parkinson’s disease. Mov Disord 26:2496–2503. doi:10.1002/mds.23932 PubMedCrossRef

Zhu W, Xie W, Pan T, Xu P, Fridkin M, Zheng H, Jankovic J, Youdim MB et al (2007) Prevention and restoration of lactacystin-induced nigrostriatal dopamine neuron degeneration by novel brain-permeable iron chelators. FASEB J 21:3835–3844. doi:10.1096/fj.07-8386com PubMedCrossRef

Zrinzo L, Zrinzo LV (2008) Surgical anatomy of the pedunculopontine and peripeduncular nuclei. Br J Neurosurg 22:S19–S24. doi:10.1080/02688690802448426 PubMedCrossRef

Title: An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease
Authors: Ilse S. Pienaar
Ian F. Harrison
Joanna L. Elson
Alexander Bury
Petter Woll
Anna Katharina Simon
David T. Dexter
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 1/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-013-0669-5

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An animal model mimicking pedunculopontine nucleus cholinergic degeneration in Parkinson’s disease

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