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

TL;DR

This study examines how drugs used to treat autism affect telomere length and related genes in rat models, revealing sex-dependent effects.

Contribution

The study identifies sex-specific impacts of nooclerin and risperidone on telomere dynamics in autism models.

Findings

Risperidone increased telomere length and gene expression in male VPA rats.

Nooclerin improved telomere length and Trf1 expression in male blood cells.

Telomere length in males correlated with reduced anxiety, and Tpp1 with stereotypical behavior.

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.

The online version contains supplementary material available at 10.1007/s12031-025-02353-4.

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