Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons

J Transl Med. 2024 Dec 30;22(1):1158. doi: 10.1186/s12967-024-06020-x.

Abstract

Taltirelin, an orally effective thyrotropin-releasing hormone analog, significantly improves motor impairments in rat models of Parkinson's disease (PD) and enhances dopamine release within the striatum. However, the underlying mechanism remains unclear. In this study, a variety of in vivo and in vitro methods, including transcriptomic analysis, were employed to elucidate the effects of Taltirelin on cellular composition and signaling pathways in the striatum of hemi-PD rats. We demonstrated that Taltirelin upregulates the expression of TRHR on striatal GABAergic neurons, which is accompanied by activation of the TRHR-MAPK-RARα-DRD2 pathway. Consequently, Taltirelin induces medium spiny neurons in the striatum to express TH. This discovery provides valuable insights into the potential application of Taltirelin in neurological disorders and offers new directions for drug development.

Keywords: Dopamine receptor D2; Taltirelin; Thyrotropin-releasing hormone receptor; Tyrosine hydroxylase.

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / metabolism
  • Gene Expression Regulation / drug effects
  • Male
  • Medium Spiny Neurons
  • Neurons / drug effects
  • Neurons / metabolism
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Rats
  • Rats, Sprague-Dawley*
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Retinoic Acid / metabolism
  • Signal Transduction / drug effects
  • Thyrotropin-Releasing Hormone / metabolism
  • Thyrotropin-Releasing Hormone / pharmacology

Substances

  • Receptors, Retinoic Acid
  • Receptors, Dopamine D2
  • Thyrotropin-Releasing Hormone