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Early life stress disrupts social behavior and prefrontal cortex parvalbumin interneurons at an earlier time-point in females than in males
Open accessAbstract
Early life stress exposure (ELS) yields risk for psychiatric disorders that might occur though a population-specific mechanism that impacts prefrontal cortical development. Sex differences in ELS effects are largely unknown and are also essential to understand social and cognitive development. ELS can cause dysfunction within parvalbumin (PVB)-containing inhibitory interneurons in the prefrontal cortex and in several prefrontal cortex-mediated behaviors including social interaction. Social behavior deficits are often the earliest observed changes in psychiatric disorders, therefore the time-course and causation of social interaction deficits after ELS are important to determine. PVB interneuron dysfunction can disrupt social behavior, and has been correlated in males with elevated markers of oxidative stress and inflammation, such as cyclooxygenase-2 after ELS. Here, we measured the effects of maternal separation ELS on social interaction behaviors in males and females. Prefrontal cortex PVB and cyclooxygenase-2 were also measured in juveniles and adolescents using Western blots. ELS led to social interaction alterations earlier in females than males. Sexually dimorphic behavioral changes were consistent with prefrontal cortex PVB loss after ELS. PVB levels were decreased in ELS-exposed juvenile females, while males exposed to ELS do not display parvalbumin decreases until adolescence. Early behavioral and PVB changes in females did not appear to be mediated through cyclooxygenase-2, since levels were not affected in ELS females. Therefore, these data suggest that ELS affects males and females differently and with distinct developmental profiles.
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“The reduction in PV+ interneuron densities we observed in the MSEW hippocampus is likely due to decreased PV protein levels rather than loss of neurons given our data on PV expression and GAD67+ cell densities, as well as previous studies showing reductions in PV protein levels due to early life adversity in the mPFC of juvenile mice (68; 69).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [69]
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Metadata
- Authors
- Holland, F. H., Ganguly, P., Potter, D. N., Chartoff, E. H., & Brenhouse, H. C.
- Affiliations
- Northeastern University (US)
- McLean Hospital (US)
- Corresponding author
- Brenhouse, Heather C.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 566
- Pages
- 131-136
- ISSN
- 0304-3940 (ISSN-L)
- PMC
- PMC4476267
- OpenAlex
- W2023467429
- Cited by
- 125
- References
- 39
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 21 · 2020: 14 · 2019: 11 · 2018: 15 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 1
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R21MH097182)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- early life stress, maternal separation, sex differences, social behavior, social interaction deficits, parvalbumin interneurons, prefrontal cortex, cyclooxygenase-2, oxidative stress, inflammation, juvenile development, adolescent development, mental illness
- MeSH terms
- Animals, Female, Interneurons, Male, Maternal Deprivation, Motor Activity, Parvalbumins, Sex Factors, Social Behavior, Stress, Psychological, Rats, Sprague-Dawley, Prefrontal Cortex, Cyclooxygenase 2
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