Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms

Abstract

Neurogenesis within the adult hippocampus is modulated by endogenous and exogenous factors. Here, we review the role of sex hormones in the regulation of adult hippocampal neurogenesis in males and females. The review is framed around the potential functional implications of sex hormone regulation of adult hippocampal neurogenesis, with a focus on cognitive function and mood regulation, which may be related to sex differences in incidence and severity of dementia and depression. We present findings from preclinical studies of endogenous fluctuations in sex hormones relating to reproductive function and ageing, and from studies of exogenous hormone manipulations. In addition, we discuss the modulating roles of sex, age, and reproductive history on the relationship between sex hormones and neurogenesis. Because sex hormones have diverse targets in the central nervous system, we overview potential mechanisms through which sex hormones may influence hippocampal neurogenesis. Lastly, we advocate for a more systematic consideration of sex and sex hormones in studying the functional implications of adult hippocampal neurogenesis.

Impact of sex and reproductive status on memory circuitry structure and function in early midlife using structural covariance analysis

“…Sex differences in hippocampus are initiated during ontogeny through interaction of exposure to sex steroids and genotype (Arnold, ). Moreover, neurogenesis after birth, prominent in hippocampus (Clelland et al, ), and potentiated by puberty (Barha & Galea, ; Duarte‐Guterman, Yagi, Chow, & Galea, ; Mahmoud, Wainwright, & Galea, ), contributes to a larger adult hippocampal volume in females than males (Giedd et al, ). Further, healthy women have shown less age‐related decline in hippocampal volume than men (Pruessner et al, ).…”

Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats

“…Estradiol influences many types of learning and memory processes (Luine et al, 1998; Goodman et al, 2004; Leuner et al, 2004; Inagaki et al, 2010; Cover et al, 2014), and studies examining estradiol’s effects on neurogenesis, dendritic branching, and long-term potentiation have demonstrated that it can alter brain structure and function as well (Galvin and Ninan, 2014; Mahmoud et al, 2016; Srivastava et al, 2013). Given the higher prevalence of fear and anxiety disorders in women compared to men, a better understanding of how estradiol can affect the neural substrates and mechanisms that control fear responses is necessary.…”

Sex Hormones and Alzheimer’s Disease

“…On the other hand, brain estrogen expression was reduced in adult female mice previously exposed to stress in adolescence but not in early adulthood which concludes that adolescent stresses suppress estrogen activities and interfere with its organizational actions to attain adult mating behavior. From these results, we can conclude that the individual's susceptibility to many neurodegenerative disorders including AD may be attained since early life and we may not be able to reverse it easily later [67,68].…”