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The Journal of Prevention of Alzheimer's Disease
Published in:

01-04-2023 | Dementia | Review

Environmental Enrichment in Murine Models and Its Translation to Human Factors Improving Conditions in Alzheimer Disease

Authors: M. F. Colavitta, L. Grasso, Francisco J. Barrantes

Published in: The Journal of Prevention of Alzheimer's Disease | Issue 2/2023

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Abstract

With the aging of the world population, there has been a notable increase in the incidence of Alzheimer disease (AD), the most prevalent neurodegenerative disease affecting the elderly. Several studies have reported a delay in the onset of AD symptoms and age-related cognitive dysfunction upon changes to a healthier lifestyle. These positive adjustments find support in the cognitive reserve hypothesis, which holds that the ability to defer disease inception and protect cognitive performance is related to healthier lifestyle habits such as cognitive and physical activity, social engagement, and sensorial stimulation. These lifestyle habits can be compounded under the umbrella of the environmental enrichment (EE) paradigm. The mechanisms underlying EE’s capacity to modulate disease expression remain unclear. Since ethical and methodological considerations rule out direct analysis of such changes in the human brain, researchers have resorted to animal models to carry out in-depth characterizations of post-EE structural and functional brain modifications using a variety of behavioral, electrophysiological, genetic, biochemical, and biophysical approaches. Moreover, given the shorter lifespan of animals compared to humans, it is possible to address the effects of aging in control and AD models. In this review we analyze and classify EE data from studies using AD murine models and compare the setup variables employed. We also delve into various aspects of neuroplasticity, under the posit that this property is the key mechanistic process underlying the benefits of EE in both animal and human subjects.
Literature
1.
Puderbaugh, M. and P.D. Emmady, Neuroplasticity, in StatPearls. 2022, StatPearls Publishing, Copyright © 2022, StatPearls Publishing LLC.: Treasure Island (FL).
2.
Kühn, S. and U. Lindenberger, Chapter 6. Research on Human Plasticity in Adulthood. 2016.
3.
Chen, X., J. Hu, and A. Sun, The Beneficial Effect of Enriched Environment on Pathogenesis of Alzheimer’s Disease. Yangtze Medicine, 2018. 02: p. 225–243.
4.
Phillips, C., Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging. Neural Plast, 2017. 2017: p. 3589271.PubMedPubMedCentral
5.
Janssen, H., et al., Translating the use of an enriched environment poststroke from bench to bedside: study design and protocol used to test the feasibility of environmental enrichment on stroke patients in rehabilitation. Int J Stroke, 2012. 7(6): p. 521–6.PubMed
6.
7.
Bekdash, R.A., The Cholinergic System, the Adrenergic System and the Neuropathology of Alzheimer’s Disease. Int J Mol Sci, 2021. 22(3).
8.
Tatulian, S.A., Challenges and hopes for Alzheimer’s disease. Drug Discov Today, 2022. 27(4): p. 1027–1043.PubMed
9.
Perneczky, R., et al., Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer’s Association Reserve, Resilience and Protective Factors Professional Interest Area working groups. BMC Medicine, 2019. 17(1): p. 47.PubMedPubMedCentral
10.
Arenaza-Urquijo, E.M., M. Wirth, and G. Chételat, Cognitive reserve and lifestyle: moving towards preclinical Alzheimer’s disease. Front Aging Neurosci, 2015. 7: p. 134.PubMedPubMedCentral
11.
Stern, Y., et al., Mechanisms underlying resilience in ageing. Nature Reviews Neuroscience, 2019. 20(4): p. 246–246.PubMed
12.
Mercerón-Martínez, D., et al., Alzheimer’s Disease, Neural Plasticity, and Functional Recovery. J Alzheimers Dis, 2021. 82(s1): p. S37–S50.PubMed
13.
Harrison, S.L., et al., Exploring strategies to operationalize cognitive reserve: A systematic review of reviews. Journal of Clinical and Experimental Neuropsychology, 2015. 37(3): p. 253–264.PubMed
14.
Cancino, M. and L. Rehbein, Factores de riesgo y precursores del Deterioro Cognitivo Leve (DCL): Una mirada sinóptica % J Terapia psicológica. 2016. 34: p. 183–189.
15.
Sampedro-Piquero, P. and A. Begega, Environmental enrichment as a positive behavioral intervention across the lifespan. Current Neuropharmacology, 2017. 15(4): p. 459–470.PubMedPubMedCentral
16.
Zhang, Y., et al., The short-term improvements of enriched environment in behaviors and pathological changes of APP/PS1 mice via regulating cytokines. Hum Vaccin Immunother, 2018. 14(8): p. 2003–2011.PubMedPubMedCentral
17.
Stern, Y., et al., Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement, 2020. 16(9): p. 1305–1311.PubMed
18.
Torres-Lista, V. and L. Giménez-Llort, Early postnatal handling and environmental enrichment improve the behavioral responses of 17-month-old 3xTg-AD and non-transgenic mice in the Forced Swim Test in a gender-dependent manner. Behavioural Processes, 2015. 120: p. 120–127.PubMed
19.
Shepherd, A., et al., Transgenic Mouse Models as Tools for Understanding How Increased Cognitive and Physical Stimulation Can Improve Cognition in Alzheimer’s Disease. Brain Plasticity, 2018. 4: p. 127–150.PubMedPubMedCentral
20.
Moga, D.C., et al., INtervention for Cognitive Reserve Enhancement in delaying the onset of Alzheimer’s Symptomatic Expression (INCREASE), a randomized controlled trial: rationale, study design, and protocol. Trials, 2019. 20(1): p. 806.PubMedPubMedCentral
21.
Lei, P., S. Ayton, and A.I. Bush, The essential elements of Alzheimer’s disease. J Biol Chem, 2021. 296: p. 100105.PubMed
22.
Mahaman, Y.A.R., et al., Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention. Ageing Res Rev, 2022. 74: p. 101544.PubMed
23.
24.
Zangrossi, A., et al., Heterogeneity and Factorial Structure in Alzheimer’s Disease: A Cognitive Perspective. J Alzheimers Dis, 2021. 83(3): p. 1341–1351.PubMed
25.
Cloak, N. and Y. Al Khalili, Behavioral And Psychological Symptoms In Dementia, in StatPearls. 2022, StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.: Treasure Island (FL).
26.
Boublay, N., A.M. Schott, and P. Krolak-Salmon, Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer’s disease: a review of 20 years of research. Eur J Neurol, 2016. 23(10): p. 1500–9.PubMed
27.
Ismail, Z., et al., Psychosis in Alzheimer disease — mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol, 2022. 18(3): p. 131–144.PubMedPubMedCentral
28.
Rodríguez-Blázquez, C., et al., Calidad de vida y estado de salud en personas mayores de 60 años con demencia institucionalizadas % J Revista Española de Salud Pública. 2015. 89: p. 51–60.
29.
Peterman, J.L., et al., Prolonged isolation stress accelerates the onset of Alzheimer’s disease-related pathology in 5xFAD mice despite running wheels and environmental enrichment. Behav Brain Res, 2020. 379: p. 112366.PubMed
30.
Calabrò, M., et al., The biological pathways of Alzheimer disease: a review. AIMS Neurosci, 2021. 8(1): p. 86–132.PubMed
31.
Montarolo, F., et al., Early enriched environment exposure protects spatial memory and accelerates amyloid plaque formation in APP(Swe)/PS1(L166P) mice. PLoS One, 2013. 8(7): p. e69381.PubMedPubMedCentral
32.
Mora, F., Successful brain aging: plasticity, environmental enrichment, and lifestyle. Dialogues Clin Neurosci, 2013. 15(1): p. 45–52.PubMedPubMedCentral
33.
Ziegler-Waldkirch, S., et al., Environmental enrichment reverses Aβ pathology during pregnancy in a mouse model of Alzheimer’s disease. Acta Neuropathol Commun, 2018. 6(1): p. 44.PubMedPubMedCentral
34.
Kuo, Y.-C. and R. Rajesh, Challenges in the treatment of Alzheimer’s disease: recent progress and treatment strategies of pharmaceuticals targeting notable pathological factors. Expert Review of Neurotherapeutics, 2019. 19(7): p. 623–652.PubMed
35.
36.
Xu, H., et al., Environmental Enrichment Potently Prevents Microglia-Mediated Neuroinflammation by Human Amyloid β-Protein Oligomers. J Neurosci, 2016. 36(35): p. 9041–56.PubMedPubMedCentral
37.
Nakano, M., An enriched environment improves cognitive impairment in an Alzheimer’s disease model by enhancing the secretion of exosomal miR-146a from the choroid plexus. 2020. 16(S2): p. e041682.
38.
Mandolesi, L., et al., Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies. Neural Plast, 2017. 2017: p. 7219461.PubMedPubMedCentral
39.
Prado Lima, M.G., et al., Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in amyloid beta neurotoxicity. Proc Natl Acad Sci U S A, 2018. 115(10): p. E2403–E2409.PubMedPubMedCentral
40.
Hüttenrauch, M., et al., Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model. Transl Psychiatry, 2016. 6(5): p. e800.PubMedPubMedCentral
41.
Bisht, K., K. Sharma, and M. Tremblay, Chronic stress as a risk factor for Alzheimer’s disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol Stress, 2018. 9: p. 9–21.PubMedPubMedCentral
42.
Snowdon, D.A., Healthy aging and dementia: findings from the Nun Study. Ann Intern Med, 2003. 139 (5 Pt 2): p. 450–4.PubMed
43.
Bauckneht, M., et al., Metabolic correlates of reserve and resilience in MCI due to Alzheimer’s Disease (AD). Alzheimers Res Ther, 2018. 10(1): p. 35.PubMedPubMedCentral
44.
Kempermann, G., Environmental enrichment, new neurons and the neurobiology of individuality. Nat Rev Neurosci, 2019. 20(4): p. 235–245.PubMed
45.
Hebb, D.O., The organization of behavior; a neuropsychological theory. The organization of behavior; a neuropsychological theory. 1949, Oxford, England: Wiley. xix, 335-xix, 335.
46.
Nithianantharajah, J. and A.J. Hannan, Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci, 2006. 7(9): p. 697–709.PubMed
47.
van Dellen, A., et al., Delaying the onset of Huntington’s in mice. Nature, 2000. 404(6779): p. 721–2.PubMed
48.
Hockly, E., et al., Environmental enrichment slows disease progression in R6/2 Huntington’s disease mice. 2002. 51(2): p. 235–242.
49.
Spires, T.L., et al., Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. J Neurosci, 2004. 24(9): p. 2270–6.PubMedPubMedCentral
50.
Arendash, G.W., et al., Environmental enrichment improves cognition in aged Alzheimer’s transgenic mice despite stable beta-amyloid deposition. Neuroreport, 2004. 15(11): p. 1751–4.PubMed
51.
Robison, L.S., et al., Environmental Enrichment: Disentangling the Influence of Novelty, Social, and Physical Activity on Cerebral Amyloid Angiopathy in a Transgenic Mouse Model. Int J Mol Sci, 2020. 21(3).
52.
Rodriguez, A., et al., Relación entre la Reserva Cognitiva y el Enriquecimiento Ambiental: Una revisión del Aporte de las Neurociencias a la comprensión del Envejecimiento Saludable. Cuadernos de Neuropsicología / Panamerican Journal of Neuropsychology, 2014. 8(2): p. 171–201.
53.
Bezzina, C., et al., Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer’s disease. Front Aging Neurosci, 2015. 7: p. 178.PubMedPubMedCentral
54.
Hu, Y.S., et al., Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PLoS One, 2013. 8(5): p. e64460.PubMedPubMedCentral
55.
Drummond, E. and T. Wisniewski, Alzheimer’s disease: experimental models and reality. Acta Neuropathol, 2017. 133(2): p. 155–175.PubMed
56.
Barrett, J.E. and P. Mcgonigle. Rodent Models for Alzheimer’s Disease in Drug Discovery. 2017.
57.
Justice, M.J. and P. Dhillon, Using the mouse to model human disease: increasing validity and reproducibility. Dis Model Mech, 2016. 9(2): p. 101–3.PubMedPubMedCentral
58.
Elder, G.A., M.A. Gama Sosa, and R. De Gasperi, Transgenic mouse models of Alzheimer’s disease. Mt Sinai J Med, 2010. 77(1): p. 69–81.PubMedPubMedCentral
59.
Holcomb, L., et al., Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med, 1998. 4(1): p. 97–100.PubMed
60.
Oddo, S., et al., Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron, 2003. 39(3): p. 409–21.PubMed
61.
Oakley, H., et al., Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer’s Disease Mutations: Potential Factors in Amyloid Plaque Formation. 2006. 26(40): p. 10129–10140.
62.
Radde, R., et al., Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep, 2006. 7(9): p. 940–6.PubMedPubMedCentral
63.
Jankowsky, J.L., et al., APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiol Aging, 2004. 25(7): p. 885–92.PubMed
64.
Li, J.Z., et al., An enriched environment delays the progression from mild cognitive impairment to Alzheimer’s disease in senescence-accelerated mouse prone 8 mice. Exp Ther Med, 2021. 22(5): p. 1320.PubMedPubMedCentral
65.
Brouillette, J., et al., Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid-β1–42 oligomers are revealed in vivo by using a novel animal model. J Neurosci, 2012. 32(23): p. 7852–61.PubMedPubMedCentral
66.
Lahiani-Cohen, I., et al., Moderate environmental enrichment mitigates tauopathy in a neurofibrillary tangle mouse model. J Neuropathol Exp Neurol, 2011. 70(7): p. 610–21.PubMed
67.
Xu, H., et al., Enriched environment enhances β-adrenergic signaling to prevent microglia inflammation by amyloid-β. EMBO Mol Med, 2018. 10(9).
68.
Li, S., et al., Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers. Neuron, 2013. 77(5): p. 929–41.PubMedPubMedCentral
69.
Wei, Z., et al., Environmental enrichment prevents Aβ oligomer-induced synaptic dysfunction through mirna-132 and hdac3 signaling pathways. Neurobiol Dis, 2020. 134: p. 104617.PubMed
70.
Dong, J., et al., Memantine combined with environmental enrichment improves spatial memory and alleviates Alzheimer’s disease-like pathology in senescence-accelerated prone-8 (SAMP8) mice. J Biomed Res, 2012. 26(6): p. 439–47.PubMedPubMedCentral
71.
Görtz, N., et al., Effects of environmental enrichment on exploration, anxiety, and memory in female TgCRND8 Alzheimer mice. Behav Brain Res, 2008. 191(1): p. 43–8.PubMed
72.
Pietropaolo, S., J. Feldon, and B.K. Yee, Environmental enrichment eliminates the anxiety phenotypes in a triple transgenic mouse model of Alzheimer’s disease. Cognitive, Affective & Behavioral Neuroscience, 2014. 14(3): p. 996–1008.
73.
Stuart, K.E., et al., Late-life environmental enrichment preserves short-term memory and may attenuate microglia in male APP/PS1 mice. Neuroscience, 2019. 408: p. 282–292.PubMed
74.
Stuart, K.E., et al., Mid-life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ-associated pathology and positively influences synaptic and cognitive health in healthy ageing. J Comp Neurol, 2017. 525(8): p. 1797–1810.PubMed
75.
Jankowsky, J.L., et al., Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J Neuropathol Exp Neurol, 2003. 62(12): p. 1220–7.PubMed
76.
Herring, A., et al., Reduction of cerebral oxidative stress following environmental enrichment in mice with Alzheimer-like pathology. Brain Pathol, 2010. 20(1): p. 166–75.PubMed
77.
Herring, A., et al., Environmental Enrichment Counteracts Alzheimer’s Neurovascular Dysfunction in TgCRND8 Mice. 2008. 18(1): p. 32–39.
78.
Barak, B., et al., Opposing actions of environmental enrichment and Alzheimer’s disease on the expression of hippocampal microRNAs in mouse models. Transl Psychiatry, 2013. 3(9): p. e304.PubMedPubMedCentral
79.
Cotel, M.C., et al., Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice. Neurobiol Aging, 2012. 33(1): p. 96–107.PubMed
80.
Griñán-Ferré, C., et al., Environmental Enrichment Improves Cognitive Deficits, AD Hallmarks and Epigenetic Alterations Presented in 5xFAD Mouse Model. Front Cell Neurosci, 2018. 12: p. 224.PubMedPubMedCentral
81.
Polito, L., et al., Environmental enrichment lessens cognitive decline in APP23 mice without affecting brain sirtuin expression. J Alzheimers Dis, 2014. 42(3): p. 851–64.PubMed
82.
Stazi, M. and O. Wirths, Physical activity and cognitive stimulation ameliorate learning and motor deficits in a transgenic mouse model of Alzheimer’s disease. Behav Brain Res, 2021. 397: p. 112951.PubMed
83.
Berardi, N., et al., Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration. J Alzheimers Dis, 2007. 11(3): p. 359–70.PubMed
84.
Cao, W.Y., et al., Role of early environmental enrichment on the social dominance tube test at adulthood in the rat. Psychopharmacology (Berl), 2017. 234(22): p. 3321–3334.PubMed
85.
Herring, A., et al., Preventive and therapeutic types of environmental enrichment counteract beta amyloid pathology by different molecular mechanisms. Neurobiol Dis, 2011. 42(3): p. 530–8.PubMed
86.
Herring, A., et al., Environmental enrichment enhances cellular plasticity in transgenic mice with Alzheimer-like pathology. Exp Neurol, 2009. 216(1): p. 184–92.PubMed
87.
Rodríguez, J.J., H.N. Noristani, and A. Verkhratsky, Microglial response to Alzheimer’s disease is differentially modulated by voluntary wheel running and enriched environments. Brain Struct Funct, 2015. 220(2): p. 941–53.PubMed
88.
Stuart, K.E., et al., Mid-Life Complex and Novel Environmental Enrichment Increase Corticosterone and Exacerbate AB Neuropathology in a Mouse Model of Alzheimer’s Disease. 2016. 12 (7, Supplement 1): p. P1039–P1040.
89.
Arranz, L., et al., Effect of environmental enrichment on the immunoendocrine aging of male and female triple-transgenic 3xTg-AD mice for Alzheimer’s disease. J Alzheimers Dis, 2011. 25(4): p. 727–37.PubMed
90.
Arranz, L., et al., Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice. Rejuvenation research, 2010. 13(4): p. 415–428.PubMed
91.
Jeong, Y.H., et al., Environmental enrichment compensates for the effects of stress on disease progression in Tg2576 mice, an Alzheimer’s disease model. J Neurochem, 2011. 119(6): p. 1282–93.PubMed
92.
Balthazar, J., et al., Enriched Environment Significantly Reduced Senile Plaques in a Transgenic Mice Model of Alzheimer’s Disease, Improving Memory. Front Aging Neurosci, 2018. 10: p. 288.PubMedPubMedCentral
93.
Huang, Y., et al., Magnesium boosts the memory restorative effect of environmental enrichment in Alzheimer’s disease mice. 2018. 24(1): p. 70–79.
94.
Kalogeraki, E., J. Pielecka-Fortuna, and S. Löwel, Environmental enrichment accelerates ocular dominance plasticity in mouse visual cortex whereas transfer to standard cages resulted in a rapid loss of increased plasticity. PLoS One, 2017. 12(10): p. e0186999.PubMedPubMedCentral
95.
Serra, L., et al., Rethinking the Reserve with a Translational Approach: Novel Ideas on the Construct and the Interventions. J Alzheimers Dis, 2018. 65(4): p. 1065–1078.PubMed
96.
Stozicka, Z., et al., Environmental Enrichment Rescues Functional Deficit and Alters Neuroinflammation in a Transgenic Model of Tauopathy. Journal of Alzheimer’s disease: JAD, 2020. 74(3): p. 951–964.PubMed
97.
Mirochnic, S., et al., Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease. Hippocampus, 2009. 19(10): p. 1008–18.PubMed
98.
Rodríguez, J.J., et al., Voluntary running and environmental enrichment restores impaired hippocampal neurogenesis in a triple transgenic mouse model of Alzheimer’s disease. Curr Alzheimer Res, 2011. 8(7): p. 707–17.PubMed
99.
Verret, L., et al., Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice. Neurobiol Aging, 2013. 34(1): p. 211–25.PubMed
100.
Jankowsky, J.L., et al., Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease. J Neurosci, 2005. 25(21): p. 5217–24.PubMedPubMedCentral
101.
Maesako, M., et al., Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice. Neurobiol Aging, 2012. 33(5): p. 1011.e11–23.PubMed
102.
Maurer, S.V. and C.L. Williams, The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells. Front Immunol, 2017. 8: p. 1489.PubMedPubMedCentral
103.
Hampel, H., et al., Reply: Optimal use of cholinergic drugs in Alzheimer’s disease. Brain, 2018. 141(9): p. e69–e69.PubMed
104.
Vallés, A.S. and F.J. Barrantes, Dendritic spine membrane proteome and its alterations in autistic spectrum disorder. Adv Protein Chem Struct Biol, 2022. 128: p. 435–474.PubMed
105.
Barrantes, F.J., V. Borroni, and S.J.F.l. Vallés, Neuronal nicotinic acetylcholine receptor-cholesterol crosstalk in Alzheimer’s disease. 2010. 584(9): p. 1856–1863.
106.
Valles, A.S., Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer’s Disease: Rationale and Current Status, ed. M.V. Borroni and F.J. Barrantes. 2014.
107.
Beauquis, J., et al., Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer’s disease. Exp Neurol, 2013. 239: p. 28–37.PubMed
108.
Blázquez, G., et al., Cognitive and emotional profiles of aged Alzheimer’s disease (3xTgAD) mice: effects of environmental enrichment and sexual dimorphism. Behav Brain Res, 2014. 268: p. 185–201.PubMed
109.
Yuste, R. and T. Bonhoeffer, Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu.Rev.Neurosci., 2001. 24: p. 1071–1089.PubMed
110.
Bear, M.F. and R.C. Malenka, Synaptic plasticity: LTP and LTD. Curr.Opin. Neurobiol., 1994. 4(3): p. 389–399.
111.
Toni, N., et al., LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature, 1999. 402(6760): p. 421–425.PubMed
112.
Lang, C., et al., Transient expansion of synaptically connected dendritic spines upon induction of hippocampal long-term potentiation. Proc.Natl.Acad. Sci.U.S.A, 2004. 101(47): p. 16665–16670.
113.
Fukazawa, Y., et al., Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron, 2003. 38(3): p. 447–460.PubMed
114.
Bonilla-Quintana, M., et al., Actin in Dendritic Spines Self-Organizes into a Critical State. 2020: p. 2020.04.22.054577.
115.
Medvedev, N.I., et al., The N-methyl-D-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat. Neuroscience, 2010. 165(4): p. 1170–1181.PubMed
116.
Zhou, Q., K.J. Homma, and M.M. Poo, Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron, 2004. 44(5): p. 749–757.PubMed
117.
Bi, G.Q. and M.M. Poo, Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci., 1998. 18(24): p. 10464–10472.PubMedPubMedCentral
118.
Tsien, J.Z., P.T. Huerta, and S. Tonegawa, The Essential Role of Hippocampal CA1 NMDA Receptor’s Dependent Synaptic Plasticity in Spatial Memory. Cell, 1996. 87(7): p. 1327–1338.PubMed
119.
Faherty, C.J., D. Kerley, and R.J. Smeyne, A Golgi-Cox morphological analysis of neuronal changes induced by environmental enrichment. Brain Res Dev Brain Res, 2003. 141(1–2): p. 55–61.PubMed
120.
Leggio, M.G., et al., Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behav Brain Res, 2005. 163(1): p. 78–90.PubMed
121.
Kempermann, G., H.G. Kuhn, and F.H. Gage, More hippocampal neurons in adult mice living in an enriched environment. Nature, 1997. 386(6624): p. 493–5.PubMed
122.
Artola, A., et al., Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Eur J Neurosci, 2006. 23(1): p. 261–72.PubMed
123.
Pham, T.M., et al., Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats. Behav Brain Res, 1999. 103(1): p. 63–70.PubMed
124.
Ickes, B.R., et al., Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol, 2000. 164(1): p. 45–52.PubMed
125.
Nithianantharajah, J., et al., Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins. 2004. 81(3): p. 200–210.
126.
Naka, F., et al., Modification of AMPA receptor properties following environmental enrichment. Brain Dev, 2005. 27(4): p. 275–8.PubMed
127.
Tang, Y.P., et al., Differential effects of enrichment on learning and memory function in NR2B transgenic mice. Neuropharmacology, 2001. 41(6): p. 779–90.PubMed
128.
Franzmeier, N., et al., The left frontal cortex supports reserve in aging by enhancing functional network efficiency. Alzheimer’s Research & Therapy, 2018. 10(1): p. 28.
129.
Moody, L., H. Chen, and Y.X. Pan, Early-Life Nutritional Programming of Cognition-The Fundamental Role of Epigenetic Mechanisms in Mediating the Relation between Early-Life Environment and Learning and Memory Process. Adv Nutr, 2017. 8(2): p. 337–350.PubMedPubMedCentral
130.
Fischer, A., Environmental enrichment as a method to improve cognitive function. What can we learn from animal models? NeuroImage, 2016. 131: p. 42–47.PubMed
131.
Gajewski, P.D., et al., Impact of Biological and Lifestyle Factors on Cognitive Aging and Work Ability in the Dortmund Vital Study: Protocol of an Interdisciplinary, Cross-sectional, and Longitudinal Study. JMIR Res Protoc, 2022. 11(3): p. e32352.PubMedPubMedCentral
132.
Koch, G. and D. Spampinato, Alzheimer disease and neuroplasticity. Handb Clin Neurol, 2022. 184: p. 473–479.PubMed
133.
Foster, P.P., K.P. Rosenblatt, and R.O. Kuljis, Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front Neurol, 2011. 2: p. 28.PubMedPubMedCentral
134.
De la Rosa, A., et al., Physical exercise in the prevention and treatment of Alzheimer’s disease. J Sport Health Sci, 2020. 9(5): p. 394–404.PubMedPubMedCentral
135.
Kępka, A., et al., Healthy Food Pyramid as Well as Physical and Mental Activity in the Prevention of Alzheimer’s Disease. 2022. 14(8): p. 1534.
136.
Bartrés-Faz, D., et al., Meaning in life: resilience beyond reserve. Alzheimer’s Research & Therapy, 2018. 10(1): p. 47.
137.
Nilsson, J. and M. Lovdén, Naming is not explaining: future directions for the “cognitive reserve” and “brain maintenance” theories. Alzheimer’s research & therapy, 2018. 10: p. 34.
138.
139.
Cabeza, R., et al., Reply to’ Mechanisms underlying resilience in ageing’. Nature Reviews Neuroscience, 2019. 20(4): p. 247–247.PubMed
140.
Cabeza, R., et al., Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing. Nature Reviews Neuroscience, 2018. 19(11): p. 701–710.PubMedPubMedCentral
141.
Soldan, A., et al., Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer’s disease. Neurobiol Aging, 2017. 60: p. 164–172.PubMedPubMedCentral
142.
Fang, Y., Guiding research and practice: a conceptual model for aerobic exercise training in Alzheimer’s disease. Am J Alzheimers Dis Other Demen, 2011. 26(3): p. 184–94.
143.
Amadasi, E., S.S. Rodríguez Espínola, and C.S. Garofalo, Condiciones de vida de las personas mayores (2017–2021): vulnerabilidades en clave de pandemia por COVID-19, EDUCA, Editor. 2022, EDSA Serie Agenda para la Equidad: Repositorio Institucional UCA.
144.
Dyer, A.H., et al., Social networks in mild-to-moderate Alzheimer disease: longitudinal relationships with dementia severity, cognitive function, and adverse events. Aging Ment Health, 2021. 25(10): p. 1923–1929.PubMed
145.
Hsiao, Y.H., C.H. Chang, and P.W. Gean, Impact of social relationships on Alzheimer’s memory impairment: mechanistic studies. J Biomed Sci, 2018. 25(1): p. 3.PubMedPubMedCentral
146.
Bruno, R.M., et al., Vascular Function Is Improved After an Environmental Enrichment Program: The Train the Brain-Mind the Vessel Study. Hypertension, 2018. 71(6): p. 1218–1225.PubMed
147.
Wilson, R.S., et al., Cognitive Activity and Onset Age of Incident Alzheimer Disease Dementia. Neurology, 2021. 97(9): p. e922–e929.PubMedPubMedCentral
148.
Ngandu, T., et al., A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet, 2015. 385(9984): p. 2255–63.PubMed
149.
Kivipelto, M., et al., World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia. Alzheimers Dement, 2020. 16(7): p. 1078–1094.PubMedPubMedCentral
150.
Rosenberg, A., et al., Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World- Wide FINGERS. J Prev Alzheimers Dis, 2020. 7(1): p. 29–36.PubMed
151.
Bott, N.T., et al., Face-to-Face and Digital Multidomain Lifestyle Interventions to Enhance Cognitive Reserve and Reduce Risk of Alzheimer’s Disease and Related Dementias: A Review of Completed and Prospective Studies. Nutrients, 2019. 11(9).
152.
Li, L., et al., Multi-component exercise training improves the physical and cognitive function of the elderly with mild cognitive impairment: a six-month randomized controlled trial. Ann Palliat Med, 2021. 10(8): p. 8919–8929.PubMed
153.
Ten Brinke, L.F., et al., The Effects of Computerized Cognitive Training With and Without Physical Exercise on Cognitive Function in Older Adults: An 8-Week Randomized Controlled Trial. J Gerontol A Biol Sci Med Sci, 2020. 75(4): p. 755–763.PubMed
154.
Yang, H.L., et al., Construction and evaluation of multidomain attention training to improve alertness attention, sustained attention, and visual-spatial attention in older adults with mild cognitive impairment: A randomized controlled trial. Int J Geriatr Psychiatry, 2020. 35(5): p. 537–546.PubMed
155.
Andersen, F., et al., The effect of stimulation therapy and donepezil on cognitive function in Alzheimer’s disease. A community based RCT with a two-by-two factorial design. BMC Neurol, 2012. 12: p. 59.PubMedPubMedCentral
156.
Matsuda, O., et al., Short-term effect of combined drug therapy and cognitive stimulation therapy on the cognitive function of Alzheimer’s disease. Psychogeriatrics, 2010. 10(4): p. 167–72.PubMed
157.
Wolozin, B., Statins and therapy of Alzheimer’s disease: questions of efficacy versus trial design. Alzheimers Res Ther, 2012. 4(1): p. 3.PubMedPubMedCentral
158.
Kandiah, N., et al., Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®. CNS neuroscience & therapeutics, 2019. 25(2): p. 288–298.
159.
Farina, N., et al., Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev, 2017. 4(4): p. Cd002854.PubMed
160.
O’Brien, J.T., et al., Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol, 2017. 31(2): p. 147–168.PubMed
161.
Bourdon, E. and J. Belmin, Enriched gardens improve cognition and independence of nursing home residents with dementia: a pilot controlled trial. Alzheimers Res Ther, 2021. 13(1): p. 116.PubMedPubMedCentral
162.
Lee, D.H., et al., Effects of Cognitive Reserve in Alzheimer’s Disease and Cognitively Unimpaired Individuals. Front Aging Neurosci, 2021. 13: p. 784054.PubMed
163.
Pettigrew, C. and A. Soldan, Defining Cognitive Reserve and Implications for Cognitive Aging. Curr Neurol Neurosci Rep, 2019. 19(1): p. 1.PubMedPubMedCentral
Metadata
Title
Environmental Enrichment in Murine Models and Its Translation to Human Factors Improving Conditions in Alzheimer Disease
Authors
M. F. Colavitta
L. Grasso
Francisco J. Barrantes
Publication date
01-04-2023
Publisher
Springer International Publishing
Keywords
Dementia
Dementia
Published in
The Journal of Prevention of Alzheimer's Disease / Issue 2/2023
Electronic ISSN: 2426-0266
DOI
https://doi.org/10.14283/jpad.2023.5

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