Protective effects of vanillic acid on autistic-like behaviors in a rat model of maternal separation stress: Behavioral, electrophysiological, molecular and histopathological alterations

• Published in: International immunopharmacology Vol. 118; p. 110112
• Main Authors: Farzan, Mahour, Farzan, Mahan, Amini-Khoei, Hossein, Shahrani, Mehrdad, Bijad, Elham, Anjomshoa, Maryam, Shabani, Sahreh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Autism Spectrum Disorder - drug therapy; Autistic Disorder - drug therapy; Disease Models, Animal; Early life stress; Immune system; Long-term potentiation; Maternal Deprivation; Nitrites; Rats; Toll-like receptor; Vanillic acid; Vanillic Acid - pharmacology; Vanillic Acid - therapeutic use; ADHD; TLR-4; PS; BBB; LTP; MDA; LPS; PRR; ASD; STZ; Vanillic acid; NLRP3; FRAP; OFT; Toll-like receptor; Immune system; MWM; AD; Long-term potentiation; MS; H&E; VA; IL-1β; BCCAO/R; TNF- α; OCD; Early life stress; PD
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110112

•Vanillic acid alleviated the anxiety-like behaviors, depression-like behaviors, and memory in rats exposed to early life maternal separation stress.•Vanillic acid decreased the expression of inflammatory genes of IL-1β, TNF-α, NLRP3, and TLR4 in the hippocampal samples.•Vanillic acid alleviated impairment in long term potentiation in hippocampus in rats exposed to early life maternal separation stress. Compounds derived from herbs exhibit a range of biological properties, including anti-inflammatory, antioxidant, and neuroprotective properties. However, the exact mechanism of action of these compounds in various neurological disorders is not fully discovered yet. Herein, the present work detected the effect of Vanillic acid (VA), a widely-used flavoring agent derived from vanillin, on autistic-like behaviors to assess the probable underlying mechanisms that mediate behavioral, electrophysiological, molecular, and histopathological alterations in the rat model of maternal separation (MS) stress. Maternal separated rats were treated with VA (25, 50, and 100 mg/kg interperitoneally for 14 days). In addition, anxiety-like, autistic-like behaviors, and learning and memory impairment were evaluated using various behavioral tests. Hippocampus samples were assessed histopathologically by H&E staining. Levels of malondialdehyde (MDA) and antioxidant capacity (by the FRAP method), as well as nitrite levels, were measured in brain tissue. Moreover, gene expression of inflammatory markers (IL-1β, TLR-4, TNF-α, and NLRP3) was evaluated in the hippocampus. Electrophysiological alterations were also estimated in the hippocampus by long-term potentiation (LTP) assessments. Results showed that VA reversed the negative effects of MS on behavior. VA increased the diameter and decreased the percentage of dark neurons in the CA3 area. Accordingly, VA decreased MDA and nitrite levels and increased the antioxidant capacity in brain samples and decreased the expression of all inflammatory genes. VA treated rats showed significant improvements in all LTP parameters. This study provided evidence suggesting a possible role for VA in preventing autism spectrum disorder (ASD) by regulating immune signaling.