Author/Editor		Rodríguez, José J.; Noristani, H. N.; Verkhratsky, Alexei
Title		Microglial response to Alzheimer's disease is differentially modulated by voluntary wheel running and enriched environments
Type		članek
Vol. and No.		Letnik 220, št. 2
Publication year		2015
Volume		str. 941-953
ISSN		1863-2653 - Brain structure & function
Language		eng
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.
Keywords		Alzheimer's disease dementia cognitive activity Alzheimerjeva bolezen demenca kognitivna dejavnost