| Summary: | Schizophrenia is a devastating neuropsychiatric disorder associated with the dysregulation of glutamate and dopamine neurotransmitter systems. The adenosine system is an important neuroregulatory system in the brain that modulates glutamate and dopamine signaling via the ubiquitously expressed adenosine receptors; however, adenosine A<sub>1</sub> and A<sub>2A</sub> receptor (A<sub>1</sub>R and A<sub>2A</sub>R) mRNA expression is poorly understood in specific cell subtypes in the frontal cortical brain regions implicated in this disorder. In this study, we assayed A<sub>1</sub>R and A<sub>2A</sub>R mRNA expression via qPCR in enriched populations of pyramidal neurons, which were isolated from postmortem anterior cingulate cortex (ACC) tissue from schizophrenia (<i>n</i> = 20) and control (<i>n</i> = 20) subjects using laser microdissection (LMD). A<sub>1</sub>R expression was significantly increased in female schizophrenia subjects compared to female control subjects (t<sub>(13)</sub> = −4.008, <i>p</i> = 0.001). A<sub>1</sub>R expression was also significantly decreased in female control subjects compared to male control subjects, suggesting sex differences in basal A<sub>1</sub>R expression (t<sub>(17)</sub> = 2.137, <i>p</i> = 0.047). A significant, positive association was found between dementia severity (clinical dementia rating (CDR) scores) and A<sub>2A</sub>R mRNA expression (Spearman’s r = 0.424, <i>p</i> = 0.009). A<sub>2A</sub>R mRNA expression was significantly increased in unmedicated schizophrenia subjects, suggesting that A<sub>2A</sub>R expression may be normalized by chronic antipsychotic treatment (F<sub>(1,14)</sub> = 9.259, <i>p</i> = 0.009). Together, these results provide novel insights into the neuronal expression of adenosine receptors in the ACC in schizophrenia and suggest that receptor expression changes may be sex-dependent and associated with cognitive decline in these subjects.
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