Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Cells. 2023 Dec 22;13(1):32. doi: 10.3390/cells13010032.
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 and A receptor (AR and AR) mRNA expression is poorly understood in specific cell subtypes in the frontal cortical brain regions implicated in this disorder. In this study, we assayed AR and AR mRNA expression via qPCR in enriched populations of pyramidal neurons, which were isolated from postmortem anterior cingulate cortex (ACC) tissue from schizophrenia ( = 20) and control ( = 20) subjects using laser microdissection (LMD). AR expression was significantly increased in female schizophrenia subjects compared to female control subjects (t = -4.008, = 0.001). AR expression was also significantly decreased in female control subjects compared to male control subjects, suggesting sex differences in basal AR expression (t = 2.137, = 0.047). A significant, positive association was found between dementia severity (clinical dementia rating (CDR) scores) and AR mRNA expression (Spearman's r = 0.424, = 0.009). AR mRNA expression was significantly increased in unmedicated schizophrenia subjects, suggesting that AR expression may be normalized by chronic antipsychotic treatment (F = 9.259, = 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.
精神分裂症是一种严重的神经精神疾病，与谷氨酸和多巴胺神经递质系统的失调有关。腺苷系统是大脑中一种重要的神经调节系统，通过广泛表达的腺苷受体调节谷氨酸和多巴胺信号；然而，在与该疾病相关的额皮质脑区的特定细胞亚型中，腺苷 A 和 A 受体（AR 和 AR）mRNA 表达的理解很差。在这项研究中，我们通过 qPCR 检测了通过激光微切割（LMD）从精神分裂症（n = 20）和对照组（n = 20）死后前扣带皮层（ACC）组织中分离的富含锥体神经元群体中的 AR 和 AR mRNA 表达。与女性对照组相比，女性精神分裂症患者的 AR 表达显著增加（t = -4.008，p = 0.001）。与男性对照组相比，女性对照组的 AR 表达也显著降低，表明 AR 表达存在性别差异（t = 2.137，p = 0.047）。AR 表达与痴呆严重程度（临床痴呆评定量表（CDR）评分）呈显著正相关（Spearman r = 0.424，p = 0.009）。未用药的精神分裂症患者的 AR mRNA 表达显著增加，表明 AR 表达可能通过慢性抗精神病治疗得到正常化（F = 9.259，p = 0.009）。这些结果为精神分裂症 ACC 中腺苷受体的神经元表达提供了新的见解，并表明受体表达变化可能依赖于性别，并与这些患者的认知能力下降有关。
