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

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 (6weeks), mature SHR (12weeks), 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.