Abstract
Pediatric traumatic brain injury (TBI) results in heightened risk for social deficits that can emerge during adolescence and adulthood. A moderate TBI in male and female rats on postnatal day 11 (equivalent to children below the age of 3) resulted in impairments in social novelty recognition, defined as the preference for interacting with a novel rat compared to a familiar rat, but not sociability, defined as the preference for interacting with a rat compared to an object in the three-chamber test when tested at 4-weeks (adolescence) and 8-weeks (adulthood) post-injury. The deficits in social recognition were not accompanied by deficits in novel object recognition memory and were associated with a decrease in the frequency of spontaneous inhibitory postsynaptic currents (IPSC) recorded from pyramidal neurons within layer II/III of the medial prefrontal cortex (mPFC). Whereas TBI did not affect the expression of oxytocin (OXT) or the oxytocin Receptor (OXT-R) mRNAs in the hypothalamus and mPFC respectively, intranasal administration of OXT prior to behavioral testing was found to reverse impairments in social novelty recognition and increase IPSC frequency in the mPFC in brain-injured animals. These results suggest that TBI-induced deficits in social behavior may be linked to increased excitability of neurons in the mPFC and suggests that the regulation of GABAergic neurotransmission in this region as a potential mechanism underlying these deficits.
Significance Statement
Traumatic brain injury (TBI) occurs in approximately half a million children below the age of 14 each year, with children younger than 4 years old at heightened risk. A younger age at injury is associated with worse behavioral and psychosocial outcomes in pediatric TBI patients, particularly as children age into adolescence and adulthood. In this study, we explored the role of oxytocin in the long-term effects of pediatric TBI on social behaviors in adolescence and adulthood. The results indicate that intranasal administration of oxytocin (OXT) improves social outcomes following pediatric TBI, potentially by increasing inhibitory neurotransmission within the medial prefrontal cortex (mPFC) and provide novel support for the use of intranasal OXT treatment to mitigate social deficits in pediatric TBI patients.
- Excitability
- GABAergic neurotransmission
- Intranasal administration
- Oxytocin
- Pediatric TBI
- Social Behavior
Footnotes
Authors report no conflicts of interest.
These studies were supported, in part, by grants from the National Institutes of Health R01 NS110898 (JH and RR) and Commonwealth Universal Research Enhancement from the Pennsylvania Department of Health SAP 410-007-9710 (RR) and SAP 410-007-7079 (RR)
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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