Background
Early developmental insults can cause dysfunction within parvalbumin (PVB)-containing
interneurons in the prefrontal cortex. The neuropsychiatric disorders associated with
such dysfunction might involve neuroinflammatory processes. Cyclooxygenase-2 (COX-2)
is a key mediator of inflammation and is therefore a potential target for preventive
treatment. Here, we investigated whether the developmental trajectories of PVB expression
and COX-2 induction in the prelimbic region of the prefrontal cortex are altered after
maternal separation stress in male rats.
Methods
Male rat pups were separated from their mother and littermates for 4 hours/day between
postnatal Days 2 and 20. Western blotting and immunohistochemistry were used to analyze
PVB and COX-2 expression in the prefrontal cortex and hippocampus. A separate cohort
of animals was treated with a COX-2 inhibitor during preadolescence and analyzed for
PVB, COX-2, and working memory performance.
Results
We demonstrate that maternal separation causes a reduction of PVB and an increase
in COX-2 expression in the prefrontal cortex in adolescence, with concurrent working
memory deficits. Parvalbumin was not affected earlier in development. Prophylactic
COX-2 inhibition preadolescence prevents PVB loss and improves working memory deficits
induced by maternal separation.
Conclusions
These data are the first to show a preventive pharmacological intervention for the
delayed effects of early life stress on prefrontal cortex interneurons and working
memory. Our results suggest a possible mechanism for the relationship between early
life stress and interneuron dysfunction in adolescence.
Key Words
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Article info
Publication history
Published online: June 17, 2011
Accepted:
May 5,
2011
Received in revised form:
April 28,
2011
Received:
March 31,
2011
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
