Sex-related differences of cAMP-specific PDE4B3 mRNA in oligodendrocytes following systemic inflammation
Glia. 2012-07-28; 60(12): 1815-1825
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Sex-related differences have been observed in the incidence and severity of
several neurological diseases and in sepsis in humans. Cyclic adenosine
monophosphate (cAMP) has been shown to play an important role in modulating the
inflammatory environment during neuroinflammation and importantly in protecting
myelin from excitotoxic cell death. Considering the sexual dimorphism in the
functional properties of oligodendrocytes and the importance of a systemic
inflammation in the progression of multiple sclerosis, we focused on identifying
possible sex-related differences in the alterations previously reported for the
two phosphodiesterase4B (PDE4B) splice-variants (PDE4B2 and PDE4B3) mRNA
expression during innate neuroinflammation. PDE4A, PDE4B, and PDE4D are present
in oligodendrocytes and we have previously reported that PDE4B3 mRNA is readily
expressed in both oligodendrocytes and neurons. In this study, we analyzed the
influence of an intraperitoneal lipopolysaccharide injection on the distribution
pattern and expression levels of the PDE4B mRNA splicing variants in both male
and female mice brains. Clear differences were observed in PDE4B2 and PDE4B3 mRNA
expression levels in males compared with females in a time-dependent manner.
Furthermore, we observed that the clear downregulation of PDE4B3 mRNA was
reflected in a lower percentage of oligodendrocytes positive for this transcript
which correlated with a decrease in inducible cAMP early repressor expression in
female corpus callosum.
Copyright © 2012 Wiley Periodicals, Inc.