Valproic Acid Induces Telomerase Reverse Transcriptase Expression during Cortical Development

Experimental Neurobiology
Ki Chan KimChan Young Shin

Abstract

The valproic acid (VPA)-induced animal model is one of the most widely utilized environmental risk factor models of autism. Autism spectrum disorder (ASD) remains an insurmountable challenge among neurodevelopmental disorders due to its heterogeneity, unresolved pathological pathways and lack of treatment. We previously reported that VPA-exposed rats and cultured rat primary neurons have increased Pax6 expression during post-midterm embryonic development which led to the sequential upregulation of glutamatergic neuronal markers. In this study, we provide experimental evidence that telomerase reverse transcriptase (TERT), a protein component of ribonucleoproteins complex of telomerase, is involved in the abnormal components caused by VPA in addition to Pax6 and its downstream signals. In embryonic rat brains and cultured rat primary neural progenitor cells (NPCs), VPA induced the increased expression of TERT as revealed by Western blot, RT-PCR, and immunostainings. The HDAC inhibitor property of VPA is responsible for the TERT upregulation. Chromatin immunoprecipitation revealed that VPA increased the histone acetylation but blocked the HDAC1 binding to both Pax6 and Tert genes. Interestingly, the VPA-induced TERT overexpression...Continue Reading

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Citations

Feb 26, 2020·Environmental Health : a Global Access Science Source·Francesca PistollatoAnna Bal-Price
Mar 26, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Abdoh TalebFeng Han
Aug 24, 2021·Frontiers in Pharmacology·Marianela Evelyn TraettaAnalía Reinés

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Methods Mentioned

BETA
PCR
acetylation
ChIP
transfection
immunoprecipitation

Software Mentioned

PASW Statistics
SPSS

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