Effects of Neuroinflammation and Autophagy on the Structure of the Blood-Brain Barrier in ADHD Model

Zhanglu Fang; Guanghong Shen; Nashwa Amin; Chengjian Lou; Changxing Wang; Marong Fang

doi:10.1016/j.neuroscience.2023.08.025

Effects of Neuroinflammation and Autophagy on the Structure of the Blood-Brain Barrier in ADHD Model

Neuroscience. 2023 Oct 15:530:17-25. doi: 10.1016/j.neuroscience.2023.08.025. Epub 2023 Aug 23.

Authors

Zhanglu Fang¹, Guanghong Shen², Nashwa Amin³, Chengjian Lou⁴, Changxing Wang⁵, Marong Fang⁶

Affiliations

¹ The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
² School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
³ Institute of System Medicine, Zhejiang University School of Medicine, Hangzhou, China; Department of Zoology, Faculty of Science, Aswan University, Egypt.
⁴ Department of Neurosurgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322022, China.
⁵ Department of Orthopedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. Electronic address: 19944010@zcmu.edu.cn.
⁶ Institute of System Medicine, Zhejiang University School of Medicine, Hangzhou, China; Department of Neurology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China. Electronic address: fangmaro@zju.edu.cn.

PMID: 37625689
DOI: 10.1016/j.neuroscience.2023.08.025

Abstract

Spontaneously hypertensive rats (SHR) are the most common animal model used to study attention deficit hyperactivity disorder (ADHD). The purpose of this study was to look at the impact of neuroinflammation and autophagy on blood-brain barrier function in the prefrontal cortex and hippocampus of ADHD rats. The rats were separated into three groups: juvenile SHR (6 weeks), mature SHR (12 weeks), and comparable age WKY groups. An open-field test was used to assess rats' ability to move on their own. Immunofluorescence was used to detect the Iba1-immunopositive microglia, ZO-1 and TNF-α. Meanwhile, the expression of p62, Beclin-1, LC3B, and MMP9, MMP2, TNF-α, ZO-1, and occludin were detected by Western blot. The results have shown that Iba1-immunopositive microglia and TNF-α protein in the brain of SHR rats were significantly increased. Moreover, autophagy of cells and the level of MMP2 and MPP9 in the prefrontal cortex and hippocampus increased in SHR rats. In addition, the expression of ZO-1 and occludin was decreased in SHR rats. To sum up, the increase of neuroinflammation and excessive autophagy were essential factors for the damage of blood-brain barrier structure and function.

Keywords: attention deficit hyperactivity disorder; autophagy; neuroinflammation; spontaneously hypertensive rat; the blood–brain barrier.