Beneficial effect of 5-HT1b/1d agonist on Parkinson's disease by modulating glutamate and reducing deposition of α-synuclein

J Biochem Mol Toxicol. 2024 Jan;38(1):e23627. doi: 10.1002/jbt.23627.

Abstract

The given investigation examined the neuroprotection role of 5-HT1b/1d agonist in reserpine induced Parkinson's disease (PD) in male Wistar rats. PD was induced in rats by reserpine at 5 mg/kg ip for 3 days and thereafter the rats were provided with the following treatments for 4 days, zolmitriptan (ZLM) group (30 mg/kg ip); STD group (levodopa + carbidopa, 200 + 5 mg/kg ip); ZLM + GA group (zolmitriptan, 30 mg/kg ip and glutamic acid, 1.5 mg/kg); ZLM + DX group (zolmitriptan, 30 mg/kg ip and dextromethorphan, 20 mg/kg ip). All the groups were then assessed for cognitive and motor functions at the end of the protocol. Moreover, oxidative stress parameters and histopathological changes were observed in rats of all treatment groups. Deposition of α-synuclein in the brain tissue was observed by silver staining. Data of this investigation revealed that motor and cognitive functions were improved in the ZLM-treated group compared with the negative control group, which was observed to be reversed in ZLM + GA group. Treatment with ZLM ameliorated oxidative stress and histopathological changes in the brain tissue of PD rats. Further, ZLM reduced the deposition of α-synuclein in PD rats, which reversed in ZLM + GA-treated group. This study concludes by stating that 5-HT1b/1d agonist can prevent neurodegeneration and reduce oxidative stress in PD rats. The probable underlying mechanism of such an effect of 5-HT1b/1d agonist could be by regulating the deposition of α-synuclein and reducing the expression of NMDA receptor.

Keywords: 5-HT1b/1d receptor; NMDA receptor; Parkinson's disease; neurodegeneration; zolmitriptan.

MeSH terms

  • Animals
  • Glutamic Acid
  • Male
  • Oxazolidinones*
  • Parkinson Disease* / drug therapy
  • Rats
  • Rats, Wistar
  • Reserpine
  • Serotonin 5-HT1 Receptor Agonists* / pharmacology
  • Tryptamines*
  • alpha-Synuclein

Substances

  • zolmitriptan
  • Serotonin 5-HT1 Receptor Agonists
  • alpha-Synuclein
  • Glutamic Acid
  • Reserpine
  • Tryptamines
  • Oxazolidinones