Enhanced Glial Reaction and Altered Neuronal Nitric Oxide Synthase are Implicated in Attention Deficit Hyperactivity Disorder

Peng Zhang; Huyue Fang; Chengjian Lou; Shan Ye; Guanghong Shen; Shijia Chen; Nashwa Amin; Benson O A Botchway; Marong Fang

doi:10.3389/fcell.2022.901093

Enhanced Glial Reaction and Altered Neuronal Nitric Oxide Synthase are Implicated in Attention Deficit Hyperactivity Disorder

Front Cell Dev Biol. 2022 Jun 21:10:901093. doi: 10.3389/fcell.2022.901093. eCollection 2022.

Authors

Peng Zhang¹, Huyue Fang¹, Chengjian Lou², Shan Ye³, Guanghong Shen⁴, Shijia Chen⁵, Nashwa Amin^{5

6}, Benson O A Botchway⁵, Marong Fang⁵

Affiliations

¹ Department of Psychiatry, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
² Department of Neurosurgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
³ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
⁴ The Affiliated People's Hospital of Hangzhou Medical College, Hangzhou Medical College, Hangzhou, China.
⁵ Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Department of Zoology, Faculty of Science, Aswan University, Aswan, Egypt.

Abstract

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.

Keywords: astrogliosis; attention deficit hyperactivity disorder (ADHD); microglia; neuronal nitric oxide synthase; spontaneously hypertensive rat.