Stress-induced inflammation and neural dysfunction - toward a cross-disease understanding of brain pathology

Abstract

Stress is a physical and mental strain caused by aversive and demanding conditions and risks mental illnesses, including depression and dementia. Rodent studies using stress models have shown that acute stress increases dendritic growth of prefrontal neurons and stress resilience via dopamine, whereas chronic stress activates microglia via the innate immune receptors TLR2/4, leading to neuronal and behavioral dysfunction. Chronic stress also promotes behavioral dysfunction by mobilizing leukocytes from the bone marrow. Thus, the role of inflammation in the brain and periphery in stress-induced neural dysfunction has been established. However, as our understanding of the biological basis of stress is still fragmentary, we and others are using single-cell omics and multi-omics analyses and molecular manipulations in a manner selective for brain regions and cell types to comprehensively identify the biological basis of stress-induced inflammation in the brain and periphery and link it to multiple behavioral domains. In this talk, I will present our recent findings on stress-induced inflammation and its relevance to neural dysfunction and discuss their implications for a cross-disease understanding of mental illnesses.