A high fat diet limits the birth and growth of new neurons in adult female, but not male, mice, according to new research published in eNeuro. Further research could inspire metabolism-based preventions and treatments for brain disorders.

Metabolic disorders like obesity and type 2 diabetes are associated with an increased risk for brain disorders ranging from depression to Alzheimer's disease. The birth and development of new neurons - adult neurogenesis - may be a link between these two types of conditions. The hippocampus, an area of the brain implicated in memory and emotional processes, is a known site of adult neurogenesis.

The researchers fed one group of mice a high fat diet and another group a normal diet for eighteen weeks. The high fat diet caused weight gain and high blood sugar in both male and female mice.

After 3 months on the diet, mice were injected with EdU, then euthanized 4 weeks later. Cell proliferation, differentiation/maturation and survival of new neurons in the dentate gyrus was assessed with immunofluorescence for EdU, Ki67, doublecortin (DCX), and NeuN. CON females had more proliferating cells (Ki67+) and neuroblasts/immature neurons (DCX+) compared to CON males; however, HF diet reduced these in females to the levels of males. Diet did not affect neurogenesis in males.

Further, the numbers of proliferating cells and immature neurons were inversely correlated with both weight gain and glucose intolerance in females only. These effects were robust in the dorsal hippocampus, which supports cognitive processes.

Assessment of microglia in the dentate gyrus using immunofluorescence for Iba1 and CD68 uncovered sex-specific effects of diet, which may contribute to observed differences in neurogenesis.

This finding offers additional insight into why women are more at risk for greater cognitive decline during Alzheimer's disease and depression.

https://www.eneuro.org/content/early/2019/12/19/ENEURO.0391-19.2019

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