Neuroprotective Potential of Tanshinone-IIA in Mitigating Propionic Acidinduced Experimental Autism-like Behavioral and Neurochemical Alterations: Insights into c-JNK and p38MAPK Pathways

Abstract

Introduction: Autism is a neurodevelopmental disorder associated with mitochondrial dysfunction, apoptosis, and neuroinflammation. These factors can lead to the overactivation of c-JNK and p38MAPK.

Methods: In rats, stereotactic intracerebroventricular (ICV) injection of propionic acid (PPA) results in autistic-like characteristics such as poor social interaction, repetitive behaviours, and restricted communication. Research has demonstrated the beneficial effects of phytochemicals derived from plants in treating neurological disorders. Tanshinone-IIA (Tan-IIA) is a chemical found in the root of Salvia miltiorrhiza. It has neuroprotective potential by inhibiting c-JNK and p38MAPK against behavioral and neurochemical alterations in PPA-induced autistic rats. We observe behavioral changes, alterations in apoptotic markers, myelin basic protein (MBP), neurofilament-Light (NEFL), inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and neurotransmitter imbalances using different brain regions (cerebral cortex, hippocampus, striatum), as well as biological samples, cerebrospinal fluid (CSF), and blood plasma.

Results: Persistent administration of 30 mg/kg and 60 mg/kg Tan-IIA via intraperitoneal injection reduced these alterations dose-dependently. Anisomycin (3 mg/kg.,i.p.) as a SAPK (c-JNK and p38MAPK) agonist was administered to assess the neuroprotective effect of Tan-IIA in autistic rats. Tan- IIA's molecular interactions with c-JNK and p38MAPK were confirmed using silico analysis. We also observed gross morphological, histopathological, and Luxol Fast Blue (LFB) myelin straining changes in whole and coronal brain sections.

Conclusion: Thus, Tan-IIA has a neuroprotective potential by inhibiting the c-JNK and p38MAPK signalling pathways, which reduces the behavioral and neurochemical abnormalities induced by PPA in adult Wistar rats, indicating that current results should be studied further for the diagnosis and treatment of autism.