Striatal Serotonin 4 Receptor is Increased in Experimental Parkinsonism and Dyskinesia

J Parkinsons Dis. 2024;14(2):261-267. doi: 10.3233/JPD-230331.

Abstract

Alterations of serotonin type 4 receptor levels are linked to mood disorders and cognitive deficits in several conditions. However, few studies have investigated 5-HT4R alterations in movement disorders. We wondered whether striatal 5-HT4R expression is altered in experimental parkinsonism. We used a brain bank tissue from a rat and a macaque model of Parkinson's disease (PD). We then investigated its in vivo PET imaging regulation in a cohort of macaques. Dopaminergic depletion increases striatal 5-HT4R in the two models, further augmented after dyskinesia-inducing L-Dopa. Pending confirmation in PD patients, the 5-HT4R might offer a therapeutic target for dampening PD's symptoms.

Keywords: L-Dopa; PET imaging; Parkinson’s disease; dyskinesia; experimental animal models; immunohistochemistry; movement disorders; parkinsonism; serotonin.

MeSH terms

  • Animals
  • Antiparkinson Agents / therapeutic use
  • Disease Models, Animal
  • Dyskinesia, Drug-Induced* / diagnostic imaging
  • Dyskinesia, Drug-Induced* / drug therapy
  • Dyskinesia, Drug-Induced* / etiology
  • Humans
  • Levodopa / therapeutic use
  • Oxidopamine
  • Parkinson Disease* / drug therapy
  • Parkinsonian Disorders* / drug therapy
  • Rats
  • Receptors, Serotonin, 5-HT4 / therapeutic use

Substances

  • Receptors, Serotonin, 5-HT4
  • Levodopa
  • Oxidopamine
  • Antiparkinson Agents