» Articles » PMID: 37524006

Sex Differences in Socioemotional Behavior and Changes in Ventral Hippocampal Transcription Across Aging in C57Bl/6J Mice

Overview
Journal Neurobiol Aging
Publisher Elsevier
Date 2023 Jul 31
PMID 37524006
Authors
Affiliations
Soon will be listed here.
Abstract

Socioemotional health is positively correlated with improved cognitive and physical aging. Despite known sex differences in socioemotional behaviors and the trajectory of aging, the interactive effects between sex and aging on socioemotional outcomes are poorly understood. We performed the most comprehensive assessment of sex differences in socioemotional behaviors in C57Bl/6J mice across aging to date. Compared to males, females exhibited decreased anxiety-like behavior and social preference but increased social recognition. With age, anxiety-like behavior, cued threat memory generalization, and social preference increased in both sexes. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed transcriptional neuropathology markers in the ventral hippocampus and found age-related changes in genes related to activated microglia, angiogenesis, and cytokines. Sex differences emerged in the timing, direction, and magnitude of these changes, independent of reproductive senescence in aged females. Interestingly, female-specific upregulation of autophagy-related genes correlated with age-related behavioral changes selectively in females. These novel findings reveal critical sex differences in trajectories of ventral hippocampal aging that may contribute to sex- and age-related differences in socioemotional outcomes.

Citing Articles

Dietary phytoestrogens recalibrate socioemotional behavior in C57Bl/6J mice in a sex- and timing-dependent manner.

Le Roux C, Farthing A, Lucas E Horm Behav. 2025; 168:105678.

PMID: 39826371 PMC: 11830535. DOI: 10.1016/j.yhbeh.2025.105678.


Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles.

Febo M, Mahar R, Rodriguez N, Buraima J, Pompilus M, Pinto A Front Aging Neurosci. 2024; 16:1356086.

PMID: 38524115 PMC: 10957556. DOI: 10.3389/fnagi.2024.1356086.


Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice.

Botterill J, Khlaifia A, Appings R, Wilkin J, Violi F, Premachandran H Neuropsychopharmacology. 2024; 49(6):993-1006.

PMID: 38233571 PMC: 11039686. DOI: 10.1038/s41386-024-01795-5.


Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.

Reed E, Keller-Norrell P Int J Mol Sci. 2023; 24(24).

PMID: 38139206 PMC: 10743742. DOI: 10.3390/ijms242417377.


Sex differences in avoidance behavior and cued threat memory dynamics in mice: Interactions between estrous cycle and genetic background.

Ryherd G, Bunce A, Edwards H, Baumgartner N, Lucas E Horm Behav. 2023; 156:105439.

PMID: 37813043 PMC: 10810684. DOI: 10.1016/j.yhbeh.2023.105439.

References
1.
Aziz W, Kraev I, Mizuno K, Kirby A, Fang T, Rupawala H . Multi-input Synapses, but Not LTP-Strengthened Synapses, Correlate with Hippocampal Memory Storage in Aged Mice. Curr Biol. 2019; 29(21):3600-3610.e4. PMC: 6839404. DOI: 10.1016/j.cub.2019.08.064. View

2.
Gemma C, Fister M, Hudson C, Bickford P . Improvement of memory for context by inhibition of caspase-1 in aged rats. Eur J Neurosci. 2005; 22(7):1751-6. DOI: 10.1111/j.1460-9568.2005.04334.x. View

3.
Tejada L, Rissman E . Sex differences in social investigation: effects of androgen receptors, hormones and test partner. J Neuroendocrinol. 2012; 24(8):1144-53. PMC: 3615635. DOI: 10.1111/j.1365-2826.2012.02322.x. View

4.
Kessler R, McGonagle K, Zhao S, Nelson C, Hughes M, Eshleman S . Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994; 51(1):8-19. DOI: 10.1001/archpsyc.1994.03950010008002. View

5.
Lu Y, Xu K, Lin D, Wang S, Fu R, Deng X . Multi-omics analysis reveals neuroinflammation, activated glial signaling, and dysregulated synaptic signaling and metabolism in the hippocampus of aged mice. Front Aging Neurosci. 2022; 14:964429. PMC: 9669972. DOI: 10.3389/fnagi.2022.964429. View