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

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 b...

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Published inJournal of molecular neuroscience Vol. 75; no. 2; p. 55
Main Authors Valeeva, Elena V., Nikitin, Dmitry O., Nikiforova, Lubov S., Semina, Irina I., Ahmetov, Ildus I.
Format Journal Article
LanguageEnglish
Published New York Springer US 24.04.2025
Springer Nature B.V
Subjects
Amitriptyline
Animal models
Animals
Antipsychotic Agents - pharmacology
Antipsychotic Agents - therapeutic use
Autism
Biomedical and Life Sciences
Biomedicine
Blood
Blood cells
Cell Biology
Drug therapy
Female
Gene expression
Genes
Hippocampus - drug effects
Hippocampus - metabolism
Male
Males
Neurochemistry
Neurology
Neurosciences
Prefrontal cortex
Prefrontal Cortex - drug effects
Prefrontal Cortex - metabolism
Proteomics
Rats
Rats, Wistar
Risperidone
Risperidone - pharmacology
Risperidone - therapeutic use
Shelterin Complex
Telomerase
Telomerase - genetics
Telomerase - metabolism
Telomere - drug effects
Telomere - metabolism
Telomere Homeostasis - drug effects
Telomere-binding protein
Telomere-Binding Proteins - genetics
Telomere-Binding Proteins - metabolism
Telomeres
TRF2 protein
Valproic acid
Valproic Acid - toxicity
Russia
Nooclerin
Autism
Amitriptyline
Risperidone
Expression genes
Telomere
Online AccessGet full text

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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.
AbstractList 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.
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.
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.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.
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.
ArticleNumber 55
Author Nikitin, Dmitry O.
Ahmetov, Ildus I.
Valeeva, Elena V.
Semina, Irina I.
Nikiforova, Lubov S.
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  organization: Central Research Laboratory, Kazan State Medical University
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Issue 2
Keywords Nooclerin
Autism
Amitriptyline
Risperidone
Expression genes
Telomere
Language English
License 2025. The Author(s).
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Snippet Telomeres are increasingly recognized for their potential role in the etiology of autism spectrum disorder (ASD) due to their involvement in cellular aging and...
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SubjectTerms Amitriptyline
Animal models
Animals
Antipsychotic Agents - pharmacology
Antipsychotic Agents - therapeutic use
Autism
Biomedical and Life Sciences
Biomedicine
Blood
Blood cells
Cell Biology
Drug therapy
Female
Gene expression
Genes
Hippocampus - drug effects
Hippocampus - metabolism
Male
Males
Neurochemistry
Neurology
Neurosciences
Prefrontal cortex
Prefrontal Cortex - drug effects
Prefrontal Cortex - metabolism
Proteomics
Rats
Rats, Wistar
Risperidone
Risperidone - pharmacology
Risperidone - therapeutic use
Shelterin Complex
Telomerase
Telomerase - genetics
Telomerase - metabolism
Telomere - drug effects
Telomere - metabolism
Telomere Homeostasis - drug effects
Telomere-binding protein
Telomere-Binding Proteins - genetics
Telomere-Binding Proteins - metabolism
Telomeres
TRF2 protein
Valproic acid
Valproic Acid - toxicity
Title Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism
URI https://link.springer.com/article/10.1007/s12031-025-02353-4
https://www.ncbi.nlm.nih.gov/pubmed/40272729
https://www.proquest.com/docview/3213515155
https://www.proquest.com/docview/3194260013
https://pubmed.ncbi.nlm.nih.gov/PMC12021733
Volume 75
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