Semaglutide ameliorated autism-like behaviors and DNA repair efficiency in male BTBR mice by recovering DNA repair gene expression.

Autor: Hussein MH; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Alameen AA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Ansari MA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., AlSharari SD; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Ahmad SF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Attia MSM; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Sarawi WS; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Nadeem A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Bakheet SA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia., Attia SM; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia. Electronic address: attiasm@ksu.edu.sa.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2024 Dec 20; Vol. 135, pp. 111091. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.pnpbp.2024.111091
Abstrakt: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is marked by impaired social interactions, and increased repetitive behaviors. There is evidence of genetic changes in ASD, and several of these altered genes are linked to the process of DNA repair. Therefore, individuals with ASD must have improved DNA repair efficiency to mitigate risks associated with ASD. Despite numerous milestones in ASD research, the disease remains incurable, with a high occurrence rate and substantial financial burdens. This motivates scientists to search for new drugs to manage the disease. Disruption of glucagon-like peptide-1 (GLP-1) signaling, a regulator in neuronal development and maintains homeostasis, has been associated with the pathogenesis and progression of several neurological disorders, such as ASD. Our study aimed to assess the impact of semaglutide, a new GLP-1 analog antidiabetic medication, on behavioral phenotypes and DNA repair efficiency in the BTBR autistic mouse model. Furthermore, we elucidated the underlying mechanism(s) responsible for the ameliorative effects of semaglutide against behavioral problems and DNA repair deficiency in BTBR mice. The current results demonstrate that repeated treatment with semaglutide efficiently decreased autism-like behaviors in BTBR mice without affecting motor performance. Semaglutide also mitigated spontaneous DNA damage and enhanced DNA repair efficiency in the BTBR mice as determined by comet assay. Moreover, administering semaglutide recovered oxidant-antioxidant balance in BTBR mice. Semaglutide restored the disrupted DNA damage/repair pathways in the BTBR mice by reducing Gadd45a expression and increasing Ogg1 and Xrcc1 expression at both the mRNA and protein levels. This suggests that semaglutide holds great potential as a novel therapeutic candidate for treating ASD traits.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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