Androgens and Adult Neurogenesis in the Hippocampus

Abstract

Adult neurogenesis in the hippocampus is modulated by steroid hormones, including androgens, in male rodents. In this review, we summarize research showing that chronic exposure to androgens, such as testosterone and dihydrotestosterone, enhances the survival of new neurons in the dentate gyrus of male, but not female, rodents, via the androgen receptor. However, the neurogenesis promoting the effect of androgens in the dentate gyrus may be limited to younger adulthood as it is not evident in middle-aged male rodents. Although direct exposure to androgens in adult or middle age does not significantly influence neurogenesis in female rodents, the aromatase inhibitor letrozole enhances neurogenesis in the hippocampus of middle-aged female mice. Unlike other androgens, androgenic anabolic steroids reduce neurogenesis in the hippocampus of male rodents. Collectively, the research indicates that the ability of androgens to enhance hippocampal neurogenesis in adult rodents is dependent on dose, androgen type, sex, duration, and age. We discuss these findings and how androgens may be influencing neuroprotection, via neurogenesis in the hippocampus, in the context of health and disease.

Evaluating the role of inhibiting the biosynthesis of estrogens in the sex-specific antidepressant-like effects of ketamine in rats

“…The copyright holder for this preprint this version posted March 30, 2023. ; https://doi.org/10.1101/2023.03.29.534716 doi: bioRxiv preprint with letrozole, in line with prior results [19,34], induced an antidepressant-like effect exclusively in female rats, which parallel the increased in testosterone levels observed 1 h post-treatment. Remarkably, the repeated administration of testosterone was previously shown to induce an antidepressant-like response in the forced-swim test [37] and to increase hippocampal neurogenesis (see review by [38]), suggesting a role for this hormone in the beneficial effects induced by letrozole in female rats.…”

“…One could speculate that letrozole could either be acting synergistically on the same molecular pathways targeted by ketamine or in additional molecular pathways, producing the enhanced physiological response observed. Moreover, and as discussed in the context of the beneficial effects of letrozole observed in females, it is possible that the increase in testosterone that accompanies aromatase inhibition might be responsible for the improved antidepressant-like response (i.e., [37][38]) induced by ketamine.…”

The Effects of Extrinsic and Intrinsic Factors on Neurogenesis

“…Surprisingly, when healthy adult mice were treated with antibiotics for 7 weeks, long-term neurogenesis in the SGZ of the DG was significantly impaired, but this change could be fully reversed through probiotic administration and voluntary exercise [276]. Moreover, an interesting study showed that C57BL/6 mice that received fecal microbiota transplantation from 5xFAD mice displayed decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment and microglial activation [277]. Gut microbes can also regulate microglia and cognitive function during malnutrition and regulate enteric neurons and glia [183,278].…”

Fundamental neurochemistry review: Old brain stories ‐ Influence of age and sex on the neurodegeneration‐associated lipid changes

“…Extensive research has focused on analyzing the role of sex steroids in determining sex differences in the hippocampus. In this brain region, a sex‐dependent regulation has been detected in cell proliferation and survival (Barker & Galea, 2008), number and density of dendrites (Mathias et al, 2010; Segarra & McEwen, 1991), patterns and density of fibers (Madeira & Paula‐Barbosa, 1993), and neurogenesis (Blankers & Galea, 2021; Duarte‐Guterman et al, 2015), among others. In addition, accumulating evidence indicates that the hippocampus is a key player in sex steroid synthesis (Brandt et al, 2020; Gall et al, 2023; Hojo et al, 2009).…”