Effects of brain estrogen receptor on depression and its mechanism of action

Depression is a refractory disease involving multiple pathologic changes, characterized by long-term disease course, low curative rate, and complex symptoms. However, the pathologic mechanism of this disease is incompletely known. Current research mainly focuses on the monoamine neurotransmitter hypothesis, neuroendocrine-related hypothesis, neuroinflammation hypothesis, and brain structure-function hypothesis. An intimate interplay exists between estrogen with the development and progression of depression. Estrogen receptors are widely distributed in the central nervous system, the expression of which can exert genetic and nongenetic effects to improve depression through regulating the level of neurotransmitters, mediating the function of the hypothalamus-pituitarium-adrenal axis, alleviating neuroinflammation, and protecting neurons. This study elaborated on the regulatory effect and mechanism of brain estrogen receptors on depression, hoping to provide new ideas for the clinical treatment of depression.