Exenatide, a GLP-1 Analog, Has Healing Effects on LPS Induced Autism Model: Inflammation, Oxidative Stress, Gliosis, Cerebral GABA and Serotonin interactions

Previous studies have established anti-inflammatory, antioxidant and neuroprotective effects of Exenatide in the central nervous system. Since these mechanisms are thought to have important roles in the pathophysiology of autism, we hypothesized that Exenatide may have healing effects in autism. We tested this hypothesis by examining the effects of Exenatide in an experimental autism model created by lipopolysaccharide (LPS) exposure in the womb, with behavioral tests, histopathological examinations and biochemical measurements. The autism model was created by administration of LPS (i.p) to pregnant rats on the 10^th day of their pregnancy at a dose of 100 µg/kg. On postnatal 21^st day, a total of 4 groups were formed from offspring with regard to sex distribution and treatment. After a 45-day treatment, behavioral analysis tests were performed on rats. Subsequently, the rats were sacrificed and biochemical analysis [superoxide dismutase, tumor necrotizing factor alpha, nerve growth factor, 5-hydroxyindoleacetic acid and glutamic acid decarboxylase-67] and histopathological analysis were performed. On the 10^th day of the intrauterine period, LPS exposure was found to disrupt behavioral findings, increase inflammation and hippocampal gliosis, and decrease 5-HIAA, GAD-67 and NGF, especially in male rats. However, among the rats exposed to LPS in the intrauterine period, recipients of Exenatide demonstrated significant amelioration of findings. Exenatide therapy shows positive effects on behavioral disorders in an LPS-induced autism model. This agent probably exerts its effects by suppressing inflammation and oxidative stress and reducing hippocampal gliosis. In addition, Exenatide has also been shown to positively affect cerebral serotonergic and GABAergic effects.

Keywords: Cerebral GABA & Serotonin; Exenatide; Gliosis; Inflammation; LPS; Oxidative Stress; autism.