Sex differences in hippocampal cognition and neurogenesis

Abstract

Sex differences are reported in hippocampal plasticity, cognition, and in a number of disorders that target the integrity of the hippocampus. For example, meta-analyses reveal that males outperform females on hippocampus-dependent tasks in rodents and in humans, furthermore women are more likely to experience greater cognitive decline in Alzheimer's disease and depression, both diseases characterized by hippocampal dysfunction. The hippocampus is a highly plastic structure, important for processing higher order information and is sensitive to the environmental factors such as stress. The structure retains the ability to produce new neurons and this process plays an important role in pattern separation, proactive interference, and cognitive flexibility. Intriguingly, there are prominent sex differences in the level of neurogenesis and the activation of new neurons in response to hippocampus-dependent cognitive tasks in rodents. However, sex differences in spatial performance can be nuanced as animal studies have demonstrated that there are task, and strategy choice dependent sex differences in performance, as well as sex differences in the subregions of the hippocampus influenced by learning. This review discusses sex differences in pattern separation, pattern completion, spatial learning, and links between adult neurogenesis and these cognitive functions of the hippocampus. We emphasize the importance of including both sexes when studying genomic, cellular, and structural mechanisms of the hippocampal function.

Loss of α7 nicotinic acetylcholine receptors in GABAergic interneurons causes sex-dependent impairments in postnatal neurogenesis and cognitive and social behavior

“…Proliferation, as measured by Ki67+ density, did not change, and there was no significant difference in immature neurons, as measured by DCX+ cell density. Additionally, within WT mice we observed fewer GFAP+ neurons in female mice relative to males, suggesting a major underlying sex difference in the level of postnatal neurogenesis, consistent with some prior findings (Juraska et al 1985; Falconer and Galea 2003; Brydges et al 2018; Yagi and Galea 2019). In a battery of behavioral tests, the most notable deficits were a male-specific deficiency in social recognition and impaired spatial learning that was strongest in the male cKO mice.…”

“…This deficit is strongest in the male cKO, although female cKO also failed to show a spatial bias for the target quadrant. Female controls showed a less pronounced spatial bias relative to control males, consistent with some prior evidence of relative spatial deficits in females (Yagi and Galea 2019). This reduced bias likely created a floor effect such that the target quadrant preference in the female cKO mice was not significantly reduced relative to female controls.…”

Brain Structure and Subclinical Symptoms: A Dimensional Perspective of Psychopathology in the Depression and Anxiety Spectrum

“…Since there is plenty of evidence for genetically driven differential neurodevelopment in men and women, especially with regard to psychopathology [67], there should be more analyses addressing the effect of gender in larger samples. For example, healthy hippocampus function as well as functional decline in illnesses like Alzheimer's disease or major depression is considerably modulated by gender, which can be demonstrated clinically, functionally, and structurally, thus hinting at gender-specific neurogenesis [68].…”

Sex-dependent effects of chronic exercise on cognitive flexibility in aging mice

“…For example, chronic exercise can alleviate the decrease of hippocampal neurogenesis and synaptic plasticity in aging rodents (Anacker & Hen, 2017;van Praag, Shubert, Zhao, & Gage, 2005). Importantly, the hippocampus is a sexually-dimorphic brain region in rodents and humans, dependent on hormonal cycle stage (reviewed in Yagi & Galea, 2019). Indeed, sex differences in hippocampus-dependent learning have been widely reported in rodents and humans, with males typically showing superior spatial learning (Jonasson, 2005;Linn & Petersen, 1985;Voyer, Voyer, & Bryden, 1995).…”