Zhang Peng, Fang Huyue, Lou Chengjian, Ye Shan, Shen Guanghong, Chen Shijia, Amin Nashwa, Botchway Benson O A, Fang Marong
Department of Psychiatry, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
Department of Neurosurgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
Front Cell Dev Biol. 2022 Jun 21;10:901093. doi: 10.3389/fcell.2022.901093. eCollection 2022.
Attention deficit hyperactivity disorder (ADHD) has a complex etiology, and its specific causal factors remain to be elucidated. Aberration of nitric oxide synthase (nNOS) and inflammation, together with astrocytic and microglial cells have been continually associated with several neurological disorders, including ADHD. Using spontaneously hypertensive rat (SHR), we investigated the changes in nNOS, inflammatory, microglial and astrocytic markers in the frontal cortex and hippocampus at three different ages: onset of hypertension stage (i.e., 6 weeks after birth of SHR), established hypertension stage (i.e., 12 weeks after birth of SHR) and senescent stage (i.e., 12 months after birth of SHR), and compared with its age-matched normotensive control, Wistar-Kyoto (WKY) rats. A significant upregulation of Iba-1 expression in the senescent stage of SHR was observed. Further, we observed an upregulated nNOS expression in both onset and established stages of SHR, and a downregulated nNOS in the senescent stage. Our study showed an age-related increment of astrogliosis in the cortex and hippocampi of aged SHR. On the basis of our results, alterations in the nNOS and Iba-1 expressions, as well as age-related astrogliosis, may contribute to ADHD pathogenesis.
注意缺陷多动障碍（ADHD）病因复杂，其具体致病因素仍有待阐明。一氧化氮合酶（nNOS）异常、炎症以及星形胶质细胞和小胶质细胞一直与包括ADHD在内的多种神经系统疾病相关。我们利用自发性高血压大鼠（SHR），研究了在三个不同年龄段（高血压发病期，即SHR出生后6周；高血压确立期，即SHR出生后12周；衰老期，即SHR出生后12个月）时，前额叶皮质和海马体中nNOS、炎症、小胶质细胞和星形胶质细胞标志物的变化，并将其与年龄匹配的正常血压对照Wistar-Kyoto（WKY）大鼠进行比较。观察到SHR衰老期Iba-1表达显著上调。此外，我们还观察到SHR发病期和确立期nNOS表达上调，而衰老期nNOS表达下调。我们的研究表明，老年SHR的皮质和海马体中星形胶质细胞增生与年龄相关。基于我们的研究结果，nNOS和Iba-1表达的改变以及与年龄相关的星形胶质细胞增生可能与ADHD的发病机制有关。
