High-fat diet suppresses the astrocytic process arborization and downregulates the glial glutamate transporters in the hippocampus of mice

Metabolic disorders induce adverse effects on brain functions. The hippocampus is one of the most vulnerable regions to metabolic disorders. Disrupted neuroplasticity is a major cause of hippocampus-related behavioral impairments, including memory loss, anxiety, and depression. Astrocytes support processes of neuroplasticity. However, whether metabolic disorders induce changes in astrocytes and their roles in affective disorders is relatively unclear. To answer this question, we fed 8-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to induce metabolic disruption and then examined their performance of hippocampus-related memory, and anxiety- and depression-like behaviors. The morphology of astrocytes and the expression of astrocytic neuroplasticity-related proteins in the hippocampus were also assessed. The results showed that HFD led to obesity, systemic insulin resistance and dysregulated lipid metabolism in mice. HFD induced depression-like behaviors, but not anxiety or memory impairment. Furthermore, HFD increased the expression of GFAP, shortened the processes of GFAP⁺ cells, and downregulated the expression of astrocytic neuroplasticity-related protein, GLAST, GLT-1, and connexin-43 in the hippocampi. In conclusion, HFD disturbs the function of hippocampal astrocytes and induces depression-like behaviors in mice. A decrease of hippocampal glutamate transporters may play a critical role in the pathogenesis of metabolic disorder-related depression.