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Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that affects neurons and glial cells and leads to dementia. Growing evidence shows that glial changes may precede neuronal alterations and behavioral impairment in the progression of the disease. The modulation of these changes could be addressed as a potential therapeutic strategy. Environmental enrichment has been classically associated to effects on neuronal morphology and function but less attention has been paid to the modulation of glia. We thus characterized astroglial changes in the hippocampus of adult PDAPP-J20 transgenic mice, a model of AD, exposed for 3 months to an enriched environment, from 5 to 8 months of age. Using confocal microscopy, three-dimensional reconstruction and Sholl analysis, we evaluated the morphology of two distinct populations of astrocytes: those associated to amyloid β plaques and those that were not. We found that plaque-associated astrocytes in PDAPP-J20 mice had an increased volume and process ramification than control astrocytes. Non-plaque-associated astrocytes showed a decrease in volume and an increase in the ramification of GFAP+ processes as compared with control astrocytes. Environmental enrichment prevented these alterations and promoted a cellular morphology similar to that found in control mice. Morphological changes in non-plaque-associated astrocytes were found also at 5 months of age, before amyloid β deposition in the hippocampus. These results suggest that glial alter…
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“Emerging evidence suggests astrocytes can adapt to lifestyle changes, offering clinical benefits30,31.”
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Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052
Neural consequences of enviromental enrichment
van Praag, H., Kempermann, G., & Gage, F. H. (2000) · Nature Reviews Neuroscience · doi:10.1038/35044558 · Cited by 2,468
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771
Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models
Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G.-Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R. C., Nicoll, R. A., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3228 · Cited by 1,123
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033
Self-citationEnvironmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Jankowsky, J. L., Melnikova, T., Fadale, D. J., Xu, G. M., Slunt, H. H., Gonzales, V., Younkin, L. H., Younkin, S. G., Borchelt, D. R., & Savonenko, A. V. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5080-04.2005 · Cited by 517
Deficient glutamate tranport is associated with neurodegeneration in Alzheimer's disease
Masliah, E., Hansen, L., Alford, M., Deteresa, R., & Mallory, M. (1996) · Annals of Neurology · doi:10.1002/ana.410400512 · Cited by 476
Carter, S. F., Schöll, M., Almkvist, O., Wall, A., Engler, H., Långström, B., & Nordberg, A. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.110.087031 · Cited by 442
Tomiyama, T., Matsuyama, S., Iso, H., Umeda, T., Takuma, H., Ohnishi, K., Ishibashi, K., Teraoka, R., Sakama, N., Yamashita, T., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5825-09.2010 · Cited by 396
Research works printed but not linked: 72
- Abramoff, 2004, Image processing with ImageJ, Biophotonics Int., 11, 36
- Akiyama, 1999, Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer's disease, Glia, 25, 324, 10.1002/(SICI)1098-1136(19990215)25:4<324::AID-GLIA2>3.0.CO;2-5 · DOI
- Arendash, 2004, Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable beta-amyloid deposition, Neuroreport, 15, 1751, 10.1097/01.wnr.0000137183.68847.4e · DOI
- Arranz, 2011, Effect of environmental enrichment on the immunoendocrine aging of male and female triple-transgenic 3xTg-AD mice for Alzheimer's disease, J. Alzheimers Dis., 25, 727, 10.3233/JAD-2011-110236 · DOI
- Beach, 1989, Patterns of gliosis in Alzheimer's disease and aging cerebrum, Glia, 2, 420, 10.1002/glia.440020605 · DOI
- Beauquis, 2010, Short-term environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice, PLoS One, 5, e13993, 10.1371/journal.pone.0013993 · DOI
- Benediktsson, 2005, Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures, J. Neurosci. Methods, 141, 41, 10.1016/j.jneumeth.2004.05.013 · DOI
- Bindu, 2007, Short-term exposure to an enriched environment enhances dendritic branching but not brain-derived neurotrophic factor expression in the hippocampus of rats with ventral subicular lesions, Neuroscience, 144, 412, 10.1016/j.neuroscience.2006.09.057 · DOI
- Boekhoorn, 2006, Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus, Neurobiol. Dis., 24, 1, 10.1016/j.nbd.2006.04.017 · DOI
- Braak, 1998, Evolution of neuronal changes in the course of Alzheimer's disease, J. Neural Transm. Suppl., 53, 127, 10.1007/978-3-7091-6467-9_11 · DOI
- Briones, 2009, Environmental experience modulates ischemia-induced amyloidogenesis and enhances functional recovery, J. Neurotrauma, 26, 613, 10.1089/neu.2008.0707 · DOI
- Costa, 2007, Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms, Neurobiol. Aging, 28, 831, 10.1016/j.neurobiolaging.2006.04.009 · DOI
- Cotel, 2012, Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice, Neurobiol. Aging, 33, 96, 10.1016/j.neurobiolaging.2010.02.012 · DOI
- de Senna, 2011, Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats, Metab. Brain Dis., 26, 269, 10.1007/s11011-011-9262-x · DOI
- Dutra, 2012, Exercise improves motor deficits and alters striatal GFAP expression in a 6-OHDA-induced rat model of Parkinson's disease, Neurol. Sci., 33, 1137, 10.1007/s10072-011-0925-5 · DOI
- Fuller, 2010, Activated astroglia during chronic inflammation in Alzheimer's disease—do they neglect their neurosupportive roles?, Mutat. Res., 690, 40, 10.1016/j.mrfmmm.2009.08.016 · DOI
- Galvan, 2006, Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664, Proc. Natl. Acad. Sci. U. S. A., 103, 7130, 10.1073/pnas.0509695103 · DOI · Paper page
- Geinisman, 1978, Hypertrophy of astroglial processes in the dentate gyrus of the senescent rat, Am. J. Anat., 153, 537, 10.1002/aja.1001530405 · DOI
- Giaume, 2007, Glia: the fulcrum of brain diseases, Cell Death Differ., 14, 1324, 10.1038/sj.cdd.4402144 · DOI
- Gundersen, 1988, The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis, APMIS, 96, 857, 10.1111/j.1699-0463.1988.tb00954.x · DOI
- Hebb, 1947, The effects of early experience on problem-solving at maturity, Am. Psychol., 2, 306
- Heneka, 2010, Neuroglia in neurodegeneration, Brain Res. Rev., 63, 189, 10.1016/j.brainresrev.2009.11.004 · DOI
- Herring, 2008, Environmental enrichment counteracts Alzheimer's neurovascular dysfunction in TgCRND8 mice, Brain Pathol., 18, 32, 10.1111/j.1750-3639.2007.00094.x · DOI
- Hou, 2011, The effects of amyloid-beta42 oligomer on the proliferation and activation of astrocytes in vitro, In Vitro Cell. Dev. Biol. Anim., 47, 573, 10.1007/s11626-011-9439-y · DOI
- Jankowsky, 2003, Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease, J. Neuropathol. Exp. Neurol., 62, 1220, 10.1093/jnen/62.12.1220 · DOI
- Jinno, 2011, Regional and laminar differences in antigen profiles and spatial distributions of astrocytes in the mouse hippocampus, with reference to aging, Neuroscience, 180, 41, 10.1016/j.neuroscience.2011.02.013 · DOI
- Kempermann, 1997, More hippocampal neurons in adult mice living in an enriched environment, Nature, 386, 493, 10.1038/386493a0 · DOI
- Kempermann, 1998, Experience-induced neurogenesis in the senescent dentate gyrus, J. Neurosci., 18, 3206, 10.1523/JNEUROSCI.18-09-03206.1998 · DOI · Paper page
- Klein, 2001, Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum?, Trends Neurosci., 24, 219, 10.1016/S0166-2236(00)01749-5 · DOI · Paper page
- Krause, 2010, Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease, Int. J. Alzheimers Dis., 10.4061/2010/732806 · DOI · Paper page
- Krech, 1962, Relations between chemistry and problem-solving among rats raised in enriched and impoverished environments, J. Comp. Physiol. Psychol., 55, 801, 10.1037/h0044220 · DOI
- Kuchibhotla, 2009, Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice, Science, 323, 1211, 10.1126/science.1169096 · DOI · Paper page
- Lazarov, 2005, Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice, Cell, 120, 701, 10.1016/j.cell.2005.01.015 · DOI · Paper page
- Li, 1997, Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression, J. Neuropathol. Exp. Neurol., 56, 901, 10.1097/00005072-199708000-00008 · DOI · Paper page
- Lue, 1999, Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease, Am. J. Pathol., 155, 853, 10.1016/S0002-9440(10)65184-X · DOI · Paper page
- Massoud, 2011, Pharmacological treatment of Alzheimer disease, Can. J. Psychiatry, 56, 579, 10.1177/070674371105601003 · DOI
- Mayeux, 2010, Clinical practice. Early Alzheimer's disease, N. Engl. J. Med., 362, 2194, 10.1056/NEJMcp0910236 · DOI
- Mirochnic, 2009, Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease, Hippocampus, 19, 1008, 10.1002/hipo.20560 · DOI
- Mucke, 2000, High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation, J. Neurosci., 20, 4050, 10.1523/JNEUROSCI.20-11-04050.2000 · DOI · Paper page
- Mulder, 2012, The effect of amyloid associated proteins on the expression of genes involved in amyloid-beta clearance by adult human astrocytes, Exp. Neurol., 233, 373, 10.1016/j.expneurol.2011.11.001 · DOI
- Murphy, 1987, Functional receptors for neurotransmitters on astroglial cells, Neuroscience, 22, 381, 10.1016/0306-4522(87)90342-3 · DOI
- Murray, 2011, The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases, Brain, 134, 3687, 10.1093/brain/awr259 · DOI
- Nagele, 2004, Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease, Neurobiol. Aging, 25, 663, 10.1016/j.neurobiolaging.2004.01.007 · DOI
- Nedergaard, 2005, Role of glial cells in cerebral ischemia, Glia, 50, 281, 10.1002/glia.20205 · DOI
- Newman, 2007, An increase in S-glutathionylated proteins in the Alzheimer's disease inferior parietal lobule, a proteomics approach, J. Neurosci. Res., 85, 1506, 10.1002/jnr.21275 · DOI
- Ohira, 2007, Truncated TrkB-T1 regulates the morphology of neocortical layer I astrocytes in adult rat brain slices, Eur. J. Neurosci., 25, 406, 10.1111/j.1460-9568.2007.05282.x · DOI
- Olabarria, 2010, Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease, Glia, 58, 831, 10.1002/glia.20967 · DOI · Paper page
- Olson, 2006, Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways, Hippocampus, 16, 250, 10.1002/hipo.20157 · DOI
- Parpura, 2012, Neuroglia at the crossroads of homeostasis, metabolism and signaling: evolution of the concept, ASN Neuro, 4, 201, 10.1042/AN20120019 · DOI
- Pekny, 2005, Astrocyte activation and reactive gliosis, Glia, 50, 427, 10.1002/glia.20207 · DOI · Paper page
- Raponi, 2007, S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage, Glia, 55, 165, 10.1002/glia.20445 · DOI
- Roberson, 2007, Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model, Science, 316, 750, 10.1126/science.1141736 · DOI · Paper page
- Rodriguez, 2009, Astroglia in dementia and Alzheimer's disease, Cell Death Differ., 16, 378, 10.1038/cdd.2008.172 · DOI
- Rolyan, 2011, Amyloid-beta protein modulates the perivascular clearance of neuronal apolipoprotein E in mouse models of Alzheimer's disease, J. Neural Transm., 118, 699, 10.1007/s00702-010-0572-7 · DOI
- Scheff, 2007, Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment, Neurology, 68, 1501, 10.1212/01.wnl.0000260698.46517.8f · DOI · Paper page
- Selkoe, 2000, Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein, Ann. N. Y. Acad. Sci., 924, 17, 10.1111/j.1749-6632.2000.tb05554.x · DOI
- Sholl, 1953, Dendritic organization in the neurons of the visual and motor cortices of the cat, J. Anat., 87, 387
- Simpson, 2011, Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype, Neurobiol. Aging, 32, 1795, 10.1016/j.neurobiolaging.2011.04.013 · DOI
- Sirevaag, 1991, Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments, Brain Res., 540, 273, 10.1016/0006-8993(91)90517-Y · DOI
- Steele, 2012, Reactive astrocytes give neurons less support: implications for Alzheimer's disease, Neurobiol. Aging, 33, 423.e1-13, 10.1016/j.neurobiolaging.2010.09.018 · DOI
- Steiner, 2004, Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice, Glia, 46, 41, 10.1002/glia.10337 · DOI
- Thal, 2012, The role of astrocytes in amyloid beta-protein toxicity and clearance, Exp. Neurol., 236, 1, 10.1016/j.expneurol.2012.04.021 · DOI
- Tian, 2005, An astrocytic basis of epilepsy, Nat. Med., 11, 973, 10.1038/nm1277 · DOI · Paper page
- Valero, 2011, Short-term environmental enrichment rescues adult neurogenesis and memory deficits in APP(Sw, Ind) transgenic mice, PLoS One, 6, e16832, 10.1371/journal.pone.0016832 · DOI
- Verret, L., Krezymon, A., Halley, H., Trouche, S., Zerwas, M., Lazouret, M., Lassalle, J.M., et al., in press. Transient enriched housing before amyloidosis onset sustains cogni-tive improvement in Tg2576 mice. Neurobiol Aging. http://dx.doi.org/10.1016/j.neurobiolaging.2012.05.013. (Electronic publication ahead of print). · DOI
- Vijayan, 1991, Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation, Exp. Neurol., 112, 72, 10.1016/0014-4886(91)90115-S · DOI
- Viola, 2009, Morphological changes in hippocampal astrocytes induced by environmental enrichment in mice, Brain Res., 1274, 47, 10.1016/j.brainres.2009.04.007 · DOI
- Webster, 2006, Astroglial activation of extracellular-regulated kinase in early stages of Alzheimer disease, J. Neuropathol. Exp. Neurol., 65, 142, 10.1097/01.jnen.0000199599.63204.6f · DOI
- Wilcock, 2006, Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain, Nat. Protoc., 1, 1591, 10.1038/nprot.2006.277 · DOI
- Williamson, 2012, Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus, Brain Behav. Immun., 26, 500, 10.1016/j.bbi.2012.01.003 · DOI
- Wyss-Coray, 2001, TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice, Nat. Med., 7, 612, 10.1038/87945 · DOI · Paper page
- Yeh, 2011, Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease, ASN Neuro, 3, 271, 10.1042/AN20110025 · DOI
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Metadata
- Authors
- Beauquis, J., Pavía, P., Pomilio, C., Vinuesa, A., Podlutskaya, N., Galvan, V., & Saravia, F.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 239
- Pages
- 28-37
- ISSN
- 0014-4886
- Cited by
- 148
- References
- 12
- Language
- en
- Funders
- Agencia Nacional de Promoción de Ciencia y Tecnología of Argentina (PICT 2011, #1012)
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