Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism

Valeeva, EV, Nikitin, DO, Nikiforova, LS, Semina, II and Ahmetov, II (2025) Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism. Journal of Molecular Neuroscience, 75. ISSN 0895-8696

Preview

Text Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase Shelterin-Related Genes in Rat Models of Autism.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Telomeres are increasingly recognized for their potential role in the etiology of autism spectrum disorder (ASD) due to their involvement in cellular aging and telomerase-shelterin function. Although shorter telomeres have been observed in individuals with ASD, studies linking telomere dynamics in blood cells and brain regions remain limited. Using the valproic acid (VPA, 500 mg/kg) rodent model, this study aimed to assess the impact of three drugs commonly used in ASD treatment (amitriptyline, risperidone, and nooclerin) on telomere length and the expression of telomerase/shelterin-related genes (Dkc1, Gar1, Pot1a, Pot1b, Tep1, Terc, Terf2ip, Tert, Tinf2, Tnks, Tpp1, Trf1, and Trf2) in blood cells, the prefrontal cortex, and hippocampus of VPA-exposed Wistar rats. Telomere length and gene expression were measured using quantitative PCR. Risperidone treatment in VPA males resulted in telomere elongation and increased expression of Tnks in blood cell and Trf1, Trf2 genes in prefrontal cortex. Nooclerin treatment also showed beneficial effects on telomere length of blood cell in males, alongside increased Trf1 expression. Long telomeres in male blood cells were associated with reduced anxiety, while a positive correlation was found between Tpp1 expression and stereotypical behavior in both male and female VPA rats. These findings suggest that nooclerin and risperidone influence telomere length and gene expression related to the telomere-telomerase complex in a sex-dependent manner, offering insights into the neurobiological mechanisms underlying ASD.

Item Type:	Article
Uncontrolled Keywords:	Hippocampus; Prefrontal Cortex; Telomere; Animals; Rats; Rats, Wistar; Valproic Acid; Risperidone; Telomerase; Telomere-Binding Proteins; Antipsychotic Agents; Female; Male; Telomere Homeostasis; Shelterin Complex; 3214 Pharmacology and Pharmaceutical Sciences; 32 Biomedical and Clinical Sciences; Mental Health; Women's Health; Genetics; Behavioral and Social Science; Intellectual and Developmental Disabilities (IDD); Pediatric; Neurosciences; Autism; Aging; Brain Disorders; 1.1 Normal biological development and functioning; 2.1 Biological and endogenous factors; Mental health; Animals; Male; Rats; Telomerase; Rats, Wistar; Female; Valproic Acid; Risperidone; Telomere-Binding Proteins; Hippocampus; Telomere; Shelterin Complex; Prefrontal Cortex; Telomere Homeostasis; Antipsychotic Agents; 1109 Neurosciences; 1702 Cognitive Sciences; Neurology & Neurosurgery; 3101 Biochemistry and cell biology; 3209 Neurosciences
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Springer
Date of acceptance:	16 April 2025
Date of first compliant Open Access:	9 July 2025
Date Deposited:	09 Jul 2025 13:04
Last Modified:	09 Jul 2025 13:15
DOI or ID number:	10.1007/s12031-025-02353-4
URI:	https://researchonline.ljmu.ac.uk/id/eprint/26747

View Item