caa a22 4500 606203281 CHVBK 20210128100957.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00429-013-0693-5 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0693-5 Microglial response to Alzheimer's disease is differentially modulated by voluntary wheel running and enriched environments [Elektronische Daten] [J. Rodríguez, H. Noristani, A. Verkhratsky] Alzheimer's disease (AD) is an untreatable neurodegenerative disease that deteriorates memory. Increased physical/cognitive activity reduces dementia risk by promoting neuronal and glial response. Although few studies have investigated microglial response in wild-type rodents following exposure to physical/cognitive stimulation, environmental-induced changes of microglia response to AD have been neglected. We investigated effects of running (RUN) and enriched (ENR) environments on numerical density (N v, #/mm3) and morphology of microglia in a triple transgenic (3×Tg-AD) mouse model of AD that closely mimics AD pathology in humans. We used immunohistochemical approach to characterise microglial domain by measuring their overall cell surface, volume and somata volume. 3×Tg-AD mice housed in standard control (STD) environment showed significant increase in microglial N v (11.7%) in CA1 stratum lacunosum moleculare (S.Mol) of the hippocampus at 12months compared to non-transgenic (non-Tg) animals. Exposure to combined RUN and ENR environments prevented an increase in microglial N v in 3×Tg-AD and reduced microglial numbers to non-Tg control levels. Interestingly, 3×Tg-AD mice housed solely in ENR environment displayed significant decrease in microglial N v in CA1 subfield (9.3% decrease), stratum oriens (11.5% decrease) and S.Mol (7.6% decrease) of the hippocampus compared to 3×Tg-AD mice housed in STD environment. Morphological analysis revealed microglial hypertrophy due to pronounced increase in microglia surface, volume and somata volume (61, 78 and 41%) in 3×Tg-AD mice housed in RUN (but not in ENR) compared to STD environment. These results indicate that exposure to RUN and ENR environments have differential effects on microglial density and activation-associated changes in microglial morphology. Springer-Verlag Berlin Heidelberg, 2013 Microglia nationallicence Alzheimer's disease nationallicence Microglial activation nationallicence Enriched environment nationallicence Voluntary running nationallicence Rodríguez J. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain aut Noristani H. INSERM U1051, Institute for Neurosciences of Montpellier, 80, av Augustin, Fliche, 34091, Montpellier Cedex 05, France aut Verkhratsky A. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain aut Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 941-953 1863-2653 220:2<941 2015 220 429 https://doi.org/10.1007/s00429-013-0693-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0693-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rodríguez J. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain aut NATIONALLICENCE 700 1- Noristani H. INSERM U1051, Institute for Neurosciences of Montpellier, 80, av Augustin, Fliche, 34091, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Verkhratsky A. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/2(2015-03-01), 941-953 1863-2653 220:2<941 2015 220 429