J Neuroinflammation 2019 Aug 19; 16(1):169
AG051496,Alzheimer’s Association Research Fellowship 2018-AARF-589154
BACKGROUND: Environmental factors are critical in the development of age-related cognitive decline and dementia. A western diet (WD) can cause nutrient deficiency and inflammation that could impact cognition directly. It is increasingly recognized that innate immune responses by brain myeloid cells, such as resident microglia, and infiltrating peripheral monocytes/macrophages may represent an essential link between a WD, cognitive decline, and dementia. Our previous data demonstrated that chronic consumption of a WD induced inflammation through brain myeloid cells in aging mice and a mouse model of Alzheimer's disease (AD). However, the subtypes of myeloid cells that contribute to the WD-induced inflammation remain unclear.
METHODS: C57BL/6J (B6), myeloid cell reporter mice (B6.Ccr2
RESULTS: Ccr2::RFP expressing myeloid cells were significantly increased in brains of WD- compared to CD-fed mice, but were not elevated in Ccr2-deficient WD-fed mice. The percent of CD11b+CD45
CONCLUSIONS: These data further support the model that peripheral myeloid cells enter the brain in response to diet-induced obesity. Elucidating their contribution to age-related cognitive decline and age-related neurodegenerative diseases should offer new avenues for therapeutic intervention in Alzheimer's disease and related dementias, where diet/obesity are major risk factors.
Yang, Hongtian; Graham, Leah C.; Reagan, Alaina M; Grabowska, Weronika; Schott, William H.; and Howell, Gareth R, "Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1, and Spp1 in western diet-induced obesity." (2019). Faculty Research 2019. 196.