Differential Impact of Adolescent or Adult Stress on Behavior and Cortical Parvalbumin Interneurons and Perineuronal Nets in Male and Female Mice

• Published in: The international journal of neuropsychopharmacology Vol. 27; no. 10; p. 1
• Main Authors: Santos-Silva, Thamyris, Souza, Beatriz Kinchin, Colodete, Débora Akemi Endo, Campos, Lara Ramos, Lima, Thaís Santos Almeida, Guimarães, Francisco S, Gomes, Felipe V
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2024
• Subjects: Age Factors; Animals; Anxiety - metabolism; Behavior, Animal - physiology; Female; Interneurons; Interneurons - metabolism; Male; Mice; Mice, Inbred C57BL; Parvalbumins - metabolism; Physiological aspects; Prefrontal Cortex - metabolism; Psychological aspects; Psychological research; Sex Characteristics; Sex differences (Psychology); Social Behavior; Stress (Psychology); Stress, Psychological - metabolism; Brazil; individual variability; neurodevelopment; sex differences; GABA interneurons
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1093/ijnp/pyae042

Abstract Background Stress has become a common public health concern, contributing to the rising prevalence of psychiatric disorders. Understanding the impact of stress considering critical variables, such as age, sex, and individual differences, is of the utmost importance for developing effective intervention strategies. Methods Stress effects (daily footshocks for 10 days) during adolescence (postnatal day [PND] 31–40) and adulthood (PND 65–74) were investigated on behavioral outcomes and parvalbumin (PV)-expressing GABAergic interneurons and their associated perineuronal nets (PNNs) in the prefrontal cortex of male and female mice 5 weeks post stress. Results In adulthood, adolescent stress induced behavioral alterations in male mice, including anxiety-like behaviors, social deficits, cognitive impairments, and altered dopamine system responsivity. Applying integrated behavioral z-score analysis, we identified sex-specific differences in response to adolescent stress, with males displaying greater vulnerability than females. Furthermore, adolescent-stressed male mice showed decreased PV+ and PNN+ cell numbers and PV+/PNN+ colocalization, while in females, adolescent stress reduced prefrontal PV+/PNN+ colocalization in the prefrontal cortex. Further analysis identified distinct behavioral clusters, with certain females demonstrating resilience to adolescent stress-induced deficits in sociability and PV+ cell number. Adult stress in male and female mice did not cause long-lasting changes in behavior and PV+ and PNN+ cell number. Conclusion Our findings indicate that the timing of stress, sex, and individual variabilities seem to be determinants for the development of behavioral changes associated with psychiatric disorders, particularly in male mice during adolescence.