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JAX Source

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.


The authors would like to thank Ted Duffy from Flow Cytometry Service at The Jackson Laboratory (JAX) for assistance with flow cytometry and FACS. We thank Heidi Munger and Genome Technologies at JAX for consultation and performing RNA sequencing. We also thank Vivek Philip, Grace Stafford and Tim Sterns from Computational Sciences at JAX for advice in RNAsequencing data analysis. This work benefitted from data assembled by the Immgen reference. Finally, we are grateful to Simon John, Jeffrey Harder, and Mimi deVries for creating the western diet used in this study and the continued collaborative discussions regarding the role of diet-induced neuroinflammation in aging and neurodegenerative diseases. SJ—your presence at JAX will be sorely missed!

This open access article is licensed under a Creative Commons Attribution 4.0 International License.