DNMT3a Downregulation Ttriggered Upregulation of GABA_A Receptor in the mPFC Promotes Paclitaxel-Induced Pain and Anxiety in Male Mice.

ABSTRACT: Chemotherapeutic agents, such as paclitaxel (PTX), induce neuroplastic changes and alter gene expression in the prefrontal cortex (PFC), which may be associated with chemotherapy-induced pain and negative emotions. Notably, DNA methylation undergoes adaptive changes in neurological disorders, emerging as a promising target for neuromodulation. In this study, systemic administration of PTX leads to a decrease in the expression of the DNA methyltransferase DNMT3a, while concurrently upregulating the expression of Gabrb1 mRNA and its encoded GABA_ARβ1 protein in the medial PFC (mPFC) of male mice. Overexpression of DNMT3a in the mPFC alleviates PTX-induced pain hypersensitivity, and anxiety-like behavior in these mice. Additionally, it reverses the PTX-induced increase in inhibitory

SUBMITTER: Tian L 

PROVIDER: S-EPMC11791956 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature