Department of Neurosciences & Psychiatry, 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. 2024 Oct 6;13(19):1657. doi: 10.3390/cells13191657.
Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia ( = 20) and sex- and age-matched control subjects without psychiatric illness ( = 20) was obtained from the Bronx-Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD). The mRNA expression levels of six key adenosine pathway components-adenosine kinase (ADK), equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), ectonucleoside triphosphate diphosphohydrolases 1 and 3 (ENTPD1 and ENTPD3), and ecto-5'-nucleotidase (NT5E)-were quantified using real-time PCR (qPCR) in neurons from these individuals. No significant mRNA expression differences were observed between the schizophrenia and control groups ( > 0.05). However, a significant sex difference was found in ADK mRNA expression, with higher levels in male compared with female subjects (Mann-Whitney U = 86; < 0.05), a finding significantly driven by disease (t = 3.289; 0.05). Correlation analyses also demonstrated significant associations ( = 12) between the expression of several adenosine pathway components ( < 0.05). In our dementia severity analysis, ENTPD1 mRNA expression was significantly higher in males in the "mild" clinical dementia rating (CDR) bin compared with males in the "none" CDR bin (F = 5.212; ). Lastly, antipsychotic analysis revealed no significant impact on the expression of adenosine pathway components between medicated and non-medicated schizophrenia subjects ( > 0.05). The observed sex-specific variations and inter-component correlations highlight the value of investigating sex differences in disease and contribute to the molecular basis of schizophrenia's pathology.
精神分裂症是一种神经精神疾病，其特征是神经递质发生改变，其中腺苷作为谷氨酸和多巴胺的调节剂，在人类大脑中发挥着至关重要但尚未被充分探索的作用。在本研究中，从布朗克斯-西奈山 NIH 大脑和组织库获得了精神分裂症患者（n = 20）和无精神疾病的年龄和性别匹配对照受试者（n = 20）的前扣带皮层（ACC）的死后人脑组织。使用激光显微切割（LMD）分离富含 ACC 锥体神经元的群体。使用实时 PCR（qPCR）定量这些个体神经元中 6 种关键腺苷途径成分（腺苷激酶（ADK）、平衡核苷转运蛋白 1 和 2（ENT1 和 ENT2）、外核苷酸三磷酸二磷酸水解酶 1 和 3（ENTPD1 和 ENTPD3）和外切 5'-核苷酸酶（NT5E）的 mRNA 表达水平。未观察到精神分裂症组和对照组之间的 mRNA 表达差异（>0.05）。然而，在 ADK mRNA 表达中发现了显著的性别差异，男性的水平高于女性（Mann-Whitney U = 86；<0.05），这一发现主要受到疾病的驱动（t = 3.289；<0.05）。相关性分析还表明，几种腺苷途径成分的表达之间存在显著关联（= 12）（<0.05）。在我们的痴呆严重程度分析中，与“无”临床痴呆评定量表（CDR）的男性相比，“轻度”CDR 分类的男性的 ENTPD1 mRNA 表达显著升高（F = 5.212；<0.05）。最后，抗精神病药物分析显示，在服用和未服用抗精神病药物的精神分裂症患者之间，腺苷途径成分的表达没有显著影响（>0.05）。观察到的性别特异性变化和成分间相关性突出了研究疾病中的性别差异的价值，并为精神分裂症病理学的分子基础做出了贡献。
