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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687129 | PMC |
| http://dx.doi.org/10.1186/s12967-024-06020-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Taltirelin induces TH expression by regulating TRHR and RARα in medium spiny neurons.
J Transl Med
December 2024
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
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.
View Article and Find Full Text PDFThyrotropin-Releasing Hormone Analog Taltirelin Inhibits Acute and Chronic Itch in Mice.
Biol Pharm Bull
November 2024
Department of Physiology, School of Allied Health Sciences, Kitasato University.
Itch is an unpleasant sensation that induces a desire to scratch. Chronic itch is accompanied by inflammatory skin diseases and causes repetitive scratching leading to tissue damage. The thyrotropin-releasing hormone analog taltirelin exerts analgesic effects on acute and chronic pain by activating the descending inhibitory systems.
View Article and Find Full Text PDFThyrotropin-releasing hormone analog as a stable upper airway-preferring respiratory stimulant with arousal properties.
J Appl Physiol (1985)
November 2022
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Taltirelin is a stable, brain-penetrating thyrotropin-releasing hormone (TRH) analog with minimal endocrine activity and potential respiratory stimulant properties. Taltirelin's receptor target shows high differential expression at the hypoglossal motor nucleus, and local taltirelin microperfusion into the hypoglossal motor nucleus causes sustained tongue motor activation compared with the transient activating effects of TRH itself. Here, we performed a randomized, within-subject, repeated-measures design over six separate study days (separated by at least 72 h) in chronically instrumented male ( = 10) and female ( = 9) rats to identify effects on sleep and breathing.
View Article and Find Full Text PDFRovatirelin ameliorates motor dysfunction in the cytosine arabinoside-induced rat model of spinocerebellar degeneration via acetylcholine and dopamine neurotransmission.
Clin Exp Pharmacol Physiol
September 2022
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Azumino, Nagano, Japan.
Thyrotropin-releasing hormone (TRH) and the TRH mimetic taltirelin have been used in Japan for the treatment of spinocerebellar degeneration (SCD), a type of progressive ataxia. A TRH mimetic, rovatirelin, ameliorates ataxia symptoms in the rolling mouse Nagoya, a hereditary SCD model. The aim of this study was to verify the effects of oral administration of rovatirelin on a cytosine arabinoside (Ara-C)-induced ataxia rat model, a sporadic SCD model characterized by gait abnormalities and falls because of cerebellar atrophy and investigate the central nervous system mechanism associated with rovatirelin-mediated amelioration of motor dysfunction in these rats.
View Article and Find Full Text PDFAre thyrotropin-releasing hormone (TRH) and analog taltirelin viable reversal agents of opioid-induced respiratory depression?
Pharmacol Res Perspect
June 2022
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Opioid-induced respiratory depression (OIRD) is a potentially life-threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin-releasing hormone (TRH). In this review, we performed a search in electronic databases and retrieved 52 papers on the effect of TRH and TRH-analogs on respiration and their efficacy in the reversal of OIRD in awake and anesthetized mammals, including humans.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!