The relationship between serotonin and BDNF (brain-derived neurotrophic factor) TrkB (tropomyosin receptor kinase B) signaling is regulated by ERβ signaling in the hippocampus. Decreased ERβ receptor activity (4) decreases BDNF levels (5) and increases 5-HT2A and MAO (monoamine oxidase) levels (7). Aging is associated with altered brain bioenergetics, leading to reduced ATP (adenosine triphosphate) levels, decreased antioxidant defense, and increased ROS production and mtDNA (mitochondrial DNA) damage (8). Estrogen deficiency exacerbates immune dysfunction by activating the pro-inflammatory cytokines IL-1, IL-6, and IL-18 (6).