Navegar

Colección

Datos Estadísticas

Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

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 alterations have an early onset in AD pathogenesis and that the exposure to an enriched environment is an appropriate strategy to reverse them. Cellular and molecular pathways involved in this regulation could constitute potential novel therapeutic targets. © 2012 Elsevier Inc.

Registro:

Documento: Artículo
Título:Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease
Autor:Beauquis, J.; Pavía, P.; Pomilio, C.; Vinuesa, A.; Podlutskaya, N.; Galvan, V.; Saravia, F.
Filiación:Laboratorio de Neurobiología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina
Department of Physiology, University of Texas Health Science Center at San Antonio, Texas, United States
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas, United States
Palabras clave:Alzheimer's disease; Astrocytes; Environmental enrichment; GFAP; Hippocampus; Transgenic mice; amyloid beta protein; amyloid precursor protein; glial fibrillary acidic protein; Alzheimer disease; amyloid plaque; analytic method; animal experiment; animal model; article; astrocyte; cell population; cell structure; cell volume; confocal microscopy; controlled study; disease association; disease model; environmental enrichment; female; hippocampus; mouse; neuroprotection; nonhuman; pathogenesis; priority journal; Sholl analysis; three dimensional imaging; transgenic mouse; treatment duration; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Astrocytes; Brain Chemistry; Coloring Agents; Congo Red; Disease Progression; Environment; Female; Glial Fibrillary Acidic Protein; Hippocampus; Humans; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments; Plaque, Amyloid
Año:2013
Volumen:239
Número:1
Página de inicio:28
Página de fin:37
DOI: http://dx.doi.org/10.1016/j.expneurol.2012.09.009
Título revista:Experimental Neurology
Título revista abreviado:Exp. Neurol.
ISSN:00144886
CODEN:EXNEA
CAS:amyloid beta protein, 109770-29-8; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Coloring Agents; Congo Red, 573-58-0; Glial Fibrillary Acidic Protein; Peptide Fragments; amyloid beta-protein (1-40); amyloid beta-protein (1-42)
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v239_n1_p28_Beauquis

Referencias:

  • Abramoff, M.D., Magelhaes, P.J., Ram, S.J., Image processing with ImageJ (2004) Biophotonics Int., 11, pp. 36-42
  • Akiyama, H., Mori, H., Saido, T., Kondo, H., Ikeda, K., McGeer, P.L., 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 (1999) Glia, 25, pp. 324-331
  • Arendash, G.W., Garcia, M.F., Costa, D.A., Cracchiolo, J.R., Wefes, I.M., Potter, H., Environmental enrichment improves cognition in aged Alzheimer's transgenic mice despite stable beta-amyloid deposition (2004) Neuroreport, 15, pp. 1751-1754
  • Arranz, L., De Castro, N.M., Baeza, I., Gimenez-Llort, L., de la, F.M., Effect of environmental enrichment on the immunoendocrine aging of male and female triple-transgenic 3xTg-AD mice for Alzheimer's disease (2011) J. Alzheimers Dis., 25, pp. 727-737
  • Beach, T.G., Walker, R., McGeer, E.G., Patterns of gliosis in Alzheimer's disease and aging cerebrum (1989) Glia, 2, pp. 420-436
  • Beauquis, J., Roig, P., De Nicola, A.F., Saravia, F., Short-term environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice (2010) PLoS One, 5, pp. e13993
  • Benediktsson, A.M., Schachtele, S.J., Green, S.H., Dailey, M.E., Ballistic labeling and dynamic imaging of astrocytes in organotypic hippocampal slice cultures (2005) J. Neurosci. Methods, 141, pp. 41-53
  • Bindu, B., Alladi, P.A., Mansooralikhan, B.M., Srikumar, B.N., Raju, T.R., Kutty, B.M., 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 (2007) Neuroscience, 144, pp. 412-423
  • Boekhoorn, K., Joels, M., Lucassen, P.J., Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus (2006) Neurobiol. Dis., 24, pp. 1-14
  • Braak, H., Braak, E., Evolution of neuronal changes in the course of Alzheimer's disease (1998) J. Neural Transm. Suppl., 53, pp. 127-140
  • Briones, T.L., Rogozinska, M., Woods, J., Environmental experience modulates ischemia-induced amyloidogenesis and enhances functional recovery (2009) J. Neurotrauma, 26, pp. 613-625
  • Carter, S.F., Scholl, M., Almkvist, O., Wall, A., Engler, H., Langstrom, B., Nordberg, A., Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG (2012) J. Nucl. Med., 53, pp. 37-46
  • Costa, D.A., Cracchiolo, J.R., Bachstetter, A.D., Hughes, T.F., Bales, K.R., Paul, S.M., Mervis, R.F., Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms (2007) Neurobiol. Aging, 28, pp. 831-844
  • Cotel, M.C., Jawhar, S., Christensen, D.Z., Bayer, T.A., Wirths, O., Environmental enrichment fails to rescue working memory deficits, neuron loss, and neurogenesis in APP/PS1KI mice (2012) Neurobiol. Aging, 33, pp. 96-107
  • de Senna, P.N., Ilha, J., Baptista, P.P., do Nascimento, P.S., Leite, M.C., Paim, M.F., Goncalves, C.A., Effects of physical exercise on spatial memory and astroglial alterations in the hippocampus of diabetic rats (2011) Metab. Brain Dis., 26, pp. 269-279
  • Dickson, D.W., Neuropathological diagnosis of Alzheimer's disease: a perspective from longitudinal clinicopathological studies (1997) Neurobiol. Aging, 18, pp. S21-S26
  • Dutra, M.F., Jaeger, M., Ilha, J., Kalil-Gaspar, P.I., Marcuzzo, S., Achaval, M., Exercise improves motor deficits and alters striatal GFAP expression in a 6-OHDA-induced rat model of Parkinson's disease (2012) Neurol. Sci., 33 (5), pp. 1137-1144
  • Fuller, S., Steele, M., Munch, G., Activated astroglia during chronic inflammation in Alzheimer's disease-do they neglect their neurosupportive roles? (2010) Mutat. Res., 690, pp. 40-49
  • Galvan, V., Gorostiza, O.F., Banwait, S., Ataie, M., Logvinova, A.V., Sitaraman, S., Carlson, E., Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664 (2006) Proc. Natl. Acad. Sci. U. S. A., 103, pp. 7130-7135
  • Geinisman, Y., Bondareff, W., Dodge, J.T., Hypertrophy of astroglial processes in the dentate gyrus of the senescent rat (1978) Am. J. Anat., 153, pp. 537-543
  • Giaume, C., Kirchhoff, F., Matute, C., Reichenbach, A., Verkhratsky, A., Glia: the fulcrum of brain diseases (2007) Cell Death Differ., 14, pp. 1324-1335
  • Gundersen, H.J., Bagger, P., Bendtsen, T.F., Evans, S.M., Korbo, L., Marcussen, N., Moller, A., The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis (1988) APMIS, 96, pp. 857-881
  • Hebb, D.O., The effects of early experience on problem-solving at maturity (1947) Am. Psychol., 2, pp. 306-307
  • Heneka, M.T., Rodriguez, J.J., Verkhratsky, A., Neuroglia in neurodegeneration (2010) Brain Res. Rev., 63, pp. 189-211
  • Herring, A., Yasin, H., Ambree, O., Sachser, N., Paulus, W., Keyvani, K., Environmental enrichment counteracts Alzheimer's neurovascular dysfunction in TgCRND8 mice (2008) Brain Pathol., 18, pp. 32-39
  • Hou, L., Liu, Y., Wang, X., Ma, H., He, J., Zhang, Y., Yu, C., The effects of amyloid-beta42 oligomer on the proliferation and activation of astrocytes in vitro (2011) In Vitro Cell. Dev. Biol. Anim., 47, pp. 573-580
  • Hsia, A.Y., Masliah, E., McConlogue, L., Yu, G.Q., Tatsuno, G., Hu, K., Kholodenko, D., Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models (1999) Proc. Natl. Acad. Sci. U. S. A., 96, pp. 3228-3233
  • Jankowsky, J.L., Xu, G., Fromholt, D., Gonzales, V., Borchelt, D.R., Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease (2003) J. Neuropathol. Exp. Neurol., 62, pp. 1220-1227
  • Jankowsky, J.L., Melnikova, T., Fadale, D.J., Xu, G.M., Slunt, H.H., Gonzales, V., Younkin, L.H., Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease (2005) J. Neurosci., 25, pp. 5217-5224
  • Jinno, S., Regional and laminar differences in antigen profiles and spatial distributions of astrocytes in the mouse hippocampus, with reference to aging (2011) Neuroscience, 180, pp. 41-52
  • Kempermann, G., Kuhn, H., Gage, F., More hippocampal neurons in adult mice living in an enriched environment (1997) Nature, 386, pp. 493-495
  • Kempermann, G., Kuhn, H.G., Gage, F.H., Experience-induced neurogenesis in the senescent dentate gyrus (1998) J. Neurosci., 18, pp. 3206-3212
  • Klein, W.L., Krafft, G.A., Finch, C.E., Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum? (2001) Trends Neurosci., 24, pp. 219-224
  • Krause, D.L., Muller, N., Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease (2010) Int. J. Alzheimers Dis., , pii:732806
  • Krech, D., Rosenzweig, M.R., Bennett, E.L., Relations between chemistry and problem-solving among rats raised in enriched and impoverished environments (1962) J. Comp. Physiol. Psychol., 55, pp. 801-807
  • Kuchibhotla, K.V., Lattarulo, C.R., Hyman, B.T., Bacskai, B.J., Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice (2009) Science, 323, pp. 1211-1215
  • Lazarov, O., Robinson, J., Tang, Y.P., Hairston, I.S., Korade-Mirnics, Z., Lee, V.M., Hersh, L.B., Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice (2005) Cell, 120, pp. 701-713
  • Li, S., Mallory, M., Alford, M., Tanaka, S., Masliah, E., Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression (1997) J. Neuropathol. Exp. Neurol., 56, pp. 901-911
  • Lue, L.F., Kuo, Y.M., Roher, A.E., Brachova, L., Shen, Y., Sue, L., Beach, T., Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease (1999) Am. J. Pathol., 155, pp. 853-862
  • Masliah, E., Alford, M., DeTeresa, R., Mallory, M., Hansen, L., Deficient glutamate transport is associated with neurodegeneration in Alzheimer's disease (1996) Ann. Neurol., 40, pp. 759-766
  • Massoud, F., Leger, G.C., Pharmacological treatment of Alzheimer disease (2011) Can. J. Psychiatry, 56, pp. 579-588
  • Mattson, M.P., Pathways towards and away from Alzheimer's disease (2004) Nature, 430, pp. 631-639
  • Mayeux, R., Clinical practice. Early Alzheimer's disease (2010) N. Engl. J. Med., 362, pp. 2194-2201
  • Mirochnic, S., Wolf, S., Staufenbiel, M., Kempermann, G., Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease (2009) Hippocampus, 19, pp. 1008-1018
  • Mucke, L., Masliah, E., Yu, G.Q., Mallory, M., Rockenstein, E.M., Tatsuno, G., Hu, K., High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation (2000) J. Neurosci., 20, pp. 4050-4058
  • Mulder, S.D., Veerhuis, R., Blankenstein, M.A., Nielsen, H.M., The effect of amyloid associated proteins on the expression of genes involved in amyloid-beta clearance by adult human astrocytes (2012) Exp. Neurol., 233, pp. 373-379
  • Murphy, S., Pearce, B., Functional receptors for neurotransmitters on astroglial cells (1987) Neuroscience, 22, pp. 381-394
  • Murray, A.D., Staff, R.T., McNeil, C.J., Salarirad, S., Ahearn, T.S., Mustafa, N., Whalley, L.J., The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases (2011) Brain, 134, pp. 3687-3696
  • Nagele, R.G., Wegiel, J., Venkataraman, V., Imaki, H., Wang, K.C., Wegiel, J., Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease (2004) Neurobiol. Aging, 25, pp. 663-674
  • Nedergaard, M., Dirnagl, U., Role of glial cells in cerebral ischemia (2005) Glia, 50, pp. 281-286
  • Newman, S.F., Sultana, R., Perluigi, M., Coccia, R., Cai, J., Pierce, W.M., Klein, J.B., An increase in S-glutathionylated proteins in the Alzheimer's disease inferior parietal lobule, a proteomics approach (2007) J. Neurosci. Res., 85, pp. 1506-1514
  • Nithianantharajah, J., Hannan, A.J., Enriched environments, experience-dependent plasticity and disorders of the nervous system (2006) Nat. Rev. Neurosci., 7, pp. 697-709
  • Ohira, K., Funatsu, N., Homma, K.J., Sahara, Y., Hayashi, M., Kaneko, T., Nakamura, S., Truncated TrkB-T1 regulates the morphology of neocortical layer I astrocytes in adult rat brain slices (2007) Eur. J. Neurosci., 25, pp. 406-416
  • Olabarria, M., Noristani, H.N., Verkhratsky, A., Rodriguez, J.J., Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease (2010) Glia, 58, pp. 831-838
  • Olson, A.K., Eadie, B.D., Ernst, C., Christie, B.R., Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways (2006) Hippocampus, 16, pp. 250-260
  • Parpura, V., Verkhratsky, A., Neuroglia at the crossroads of homeostasis, metabolism and signaling: evolution of the concept (2012) ASN Neuro, 4 (4), pp. 201-205
  • Pekny, M., Nilsson, M., Astrocyte activation and reactive gliosis (2005) Glia, 50, pp. 427-434
  • Querfurth, H.W., LaFerla, F.M., Alzheimer's disease (2010) N. Engl. J. Med., 362, pp. 329-344
  • Raponi, E., Agenes, F., Delphin, C., Assard, N., Baudier, J., Legraverend, C., Deloulme, J.C., S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage (2007) Glia, 55, pp. 165-177
  • Roberson, E.D., Scearce-Levie, K., Palop, J.J., Yan, F., Cheng, I.H., Wu, T., Gerstein, H., Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model (2007) Science, 316, pp. 750-754
  • Rodriguez, J.J., Olabarria, M., Chvatal, A., Verkhratsky, A., Astroglia in dementia and Alzheimer's disease (2009) Cell Death Differ., 16, pp. 378-385
  • Rolyan, H., Feike, A.C., Upadhaya, A.R., Waha, A., Van Dooren, T., Haass, C., Birkenmeier, G., Amyloid-beta protein modulates the perivascular clearance of neuronal apolipoprotein E in mouse models of Alzheimer's disease (2011) J. Neural Transm., 118, pp. 699-712
  • Scheff, S.W., Price, D.A., Schmitt, F.A., DeKosky, S.T., Mufson, E.J., Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment (2007) Neurology, 68, pp. 1501-1508
  • Selkoe, D.J., Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein (2000) Ann. N. Y. Acad. Sci., 924, pp. 17-25
  • Sholl, D.A., Dendritic organization in the neurons of the visual and motor cortices of the cat (1953) J. Anat., 87, pp. 387-406
  • Simpson, J.E., Ince, P.G., Shaw, P.J., Heath, P.R., Raman, R., Garwood, C.J., Gelsthorpe, C., Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype (2011) Neurobiol. Aging, 32, pp. 1795-1807
  • Sirevaag, A.M., Greenough, W.T., Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments (1991) Brain Res., 540, pp. 273-278
  • Spilman, P., Podlutskaya, N., Hart, M.J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease (2010) PLoS One, 5, pp. e9979
  • Steele, M.L., Robinson, S.R., Reactive astrocytes give neurons less support: implications for Alzheimer's disease (2012) Neurobiol. Aging, 33 (2), pp. 423.e1-13
  • Steiner, B., Kronenberg, G., Jessberger, S., Brandt, M.D., Reuter, K., Kempermann, G., Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice (2004) Glia, 46, pp. 41-52
  • Thal, D.R., The role of astrocytes in amyloid beta-protein toxicity and clearance (2012) Exp. Neurol., 236, pp. 1-5
  • Thal, D.R., Schultz, C., Dehghani, F., Yamaguchi, H., Braak, H., Braak, E., Amyloid beta-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex (2000) Acta Neuropathol., 100, pp. 608-617
  • Tian, G.F., Azmi, H., Takano, T., Xu, Q., Peng, W., Lin, J., Oberheim, N., An astrocytic basis of epilepsy (2005) Nat. Med., 11, pp. 973-981
  • Tomiyama, T., Matsuyama, S., Iso, H., Umeda, T., Takuma, H., Ohnishi, K., Ishibashi, K., A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo (2010) J. Neurosci., 30, pp. 4845-4856
  • Valero, J., Espana, J., Parra-Damas, A., Martin, E., Rodriguez-Alvarez, J., Saura, C.A., Short-term environmental enrichment rescues adult neurogenesis and memory deficits in APP(Sw, Ind) transgenic mice (2011) PLoS One, 6, pp. e16832
  • van Praag, H., Kempermann, G., Gage, F.H., Neural consequences of environmental enrichment (2000) Nat. Rev. Neurosci., 1, pp. 191-198
  • Verret, L., Krezymon, A., Halley, H., Trouche, S., Zerwas, M., Lazouret, M., Lassalle, J.M., 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, in press. (Electronic publication ahead of print)
  • Vijayan, V.K., Geddes, J.W., Anderson, K.J., Chang-Chui, H., Ellis, W.G., Cotman, C.W., Astrocyte hypertrophy in the Alzheimer's disease hippocampal formation (1991) Exp. Neurol., 112, pp. 72-78
  • Viola, G.G., Rodrigues, L., Americo, J.C., Hansel, G., Vargas, R.S., Biasibetti, R., Swarowsky, A., Morphological changes in hippocampal astrocytes induced by environmental enrichment in mice (2009) Brain Res., 1274, pp. 47-54
  • Webster, B., Hansen, L., Adame, A., Crews, L., Torrance, M., Thal, L., Masliah, E., Astroglial activation of extracellular-regulated kinase in early stages of Alzheimer disease (2006) J. Neuropathol. Exp. Neurol., 65, pp. 142-151
  • Wilcock, D.M., Gordon, M.N., Morgan, D., Quantification of cerebral amyloid angiopathy and parenchymal amyloid plaques with Congo red histochemical stain (2006) Nat. Protoc., 1, pp. 1591-1595
  • Williamson, L.L., Chao, A., Bilbo, S.D., Environmental enrichment alters glial antigen expression and neuroimmune function in the adult rat hippocampus (2012) Brain Behav. Immun., 26, pp. 500-510
  • Wyss-Coray, T., Lin, C., Yan, F., Yu, G.Q., Rohde, M., McConlogue, L., Masliah, E., TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice (2001) Nat. Med., 7, pp. 612-618
  • Yeh, C.Y., Vadhwana, B., Verkhratsky, A., Rodriguez, J.J., Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease (2011) ASN Neuro, 3, pp. 271-279

Citas:

---------- APA ----------
Beauquis, J., Pavía, P., Pomilio, C., Vinuesa, A., Podlutskaya, N., Galvan, V. & Saravia, F. (2013) . Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease. Experimental Neurology, 239(1), 28-37.
http://dx.doi.org/10.1016/j.expneurol.2012.09.009
---------- CHICAGO ----------
Beauquis, J., Pavía, P., Pomilio, C., Vinuesa, A., Podlutskaya, N., Galvan, V., et al. "Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease" . Experimental Neurology 239, no. 1 (2013) : 28-37.
http://dx.doi.org/10.1016/j.expneurol.2012.09.009
---------- MLA ----------
Beauquis, J., Pavía, P., Pomilio, C., Vinuesa, A., Podlutskaya, N., Galvan, V., et al. "Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease" . Experimental Neurology, vol. 239, no. 1, 2013, pp. 28-37.
http://dx.doi.org/10.1016/j.expneurol.2012.09.009
---------- VANCOUVER ----------
Beauquis, J., Pavía, P., Pomilio, C., Vinuesa, A., Podlutskaya, N., Galvan, V., et al. Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease. Exp. Neurol. 2013;239(1):28-37.
http://dx.doi.org/10.1016/j.expneurol.2012.09.009