Effects of different doses of lithium on the central nervous system in the rat valproic acid model of autism

Abstract

Epidemiological studies have shown that low doses of lithium in the environment can have beneficial effects on mental health. Autism spectrum disorder, a neurodevelopmental disorder in which patients exhibit abnormal behaviors, pharmacological interventions usually relied on a range of psychotropic medications. However, such medications often produce severe side effects or are ineffective in symptoms. Finding alternative ways to improve abnormal behaviors in individuals with autism are warranted, in which case lithium may be a relatively safe and effective medication. Lithium salt therapy is used to treat a variety of neuropsychiatric disorders and has neuroprotective effects. In this study, we investigated the effects of different doses of lithium on neurobehavioural disorders using the rat model of autism established by valproic acid (VPA) injection. Lithium was observed to have an ameliorative effect on the social cognitive, social memory and anxiety levels in the rat model of autism. Immunofluorescence staining showed that subchronic LiCl administration (1.0 mmol/kg) significantly reduced the number of Iba-1 positive cells in the CA1 region of the hippocampus in VPA group and brought it close to the levels of control group. Significantly lower levels of the pro-inflammatory marker IL-6 were observed in the hippocampus and serum after lithium treatment. In addition, the lithium treatment increased the levels of H3K9 acetylation in the hippocampus of VPA-exposed rats. The results showed a defensive effect of environment-related lithium exposure doses on neurobehavioural deficits in the rat valproic acid model of autism, suggesting that it may be a potential drug for the treatment of autism.