title: Microglial response to Alzheimer's disease is differentially modulated by voluntary wheel running and enriched environments.
abstract: 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, #/mm(3)) 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 12 months 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.
authors.affiliation: IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain, j.rodriguez-arellano@ikerbasque.org.
authors.forename: J J
authors.initials: JJ
authors.lastname: Rodríguez
authors.forename: H N
authors.initials: HN
authors.lastname: Noristani
authors.forename: A
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004777:Environment; D005106:Exploratory Behavior; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006799:Housing, Animal; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D016874:Neurofibrillary Tangles; D010805:Physical Conditioning, Animal; D058225:Plaque, Amyloid; D012420:Running; D013997:Time Factors; D014836:Volition