Impact of 6-hydroxydopamine on agonist-induced human platelet functional parameters: An explanation for platelet impairment in Parkinson's disease

Neuroscience. 2024 Nov 1:559:237-248. doi: 10.1016/j.neuroscience.2024.09.015. Epub 2024 Sep 10.

Abstract

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease worldwide, which worsens with advancing age. It is a common movement disorder and is often associated with several vascular diseases with decreased stroke frequency. Circulating platelets substantially regulate vascular complications, including stroke, and share striking similarities with PD neurons. Although structural alterations in platelets are well-documented in PD, their functional parameters remain unclear. This study aimed to investigate the functional abnormalities in platelets associated with PD by evaluating key functional aspects such as adhesion, activation, secretion, aggregation, and clot retraction. To achieve this, we treated human blood platelets with 6-hydroxydopamine or 6-OHDA, that selectively destroys dopaminergic neurons, thereby creating an in vitro experimental model that closely resembles the pathogenic environment in PD, and examine its impact on platelet functions. In our study, platelet adhesion was assessed and further evaluated by a microplate reader, activation and secretion by a flow cytometer, aggregation by aggregometer, and clot retraction by Sonoclot. Phase-contrast and confocal microscopic studies further verified the results from the above experiments. Our findings showed that 6-OHDA treatment significantly inhibited thrombin (a platelet agonist)-induced functions, including adhesion, activation, aggregation, secretion, and clot retraction in human-washed platelets. In summary, this research provides pioneering evidence that 6-OHDA induces abnormal platelet functions, shedding light on the previously unexplored processes by which 6-OHDA affects platelet activity.

Keywords: 6-hydroxydopamine; Activation; Aggregation; Blood platelet; Clot retraction; Parkinson’s disease.

MeSH terms

  • Blood Platelets* / drug effects
  • Blood Platelets* / metabolism
  • Clot Retraction / drug effects
  • Humans
  • Oxidopamine* / pharmacology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Platelet Activation / drug effects
  • Platelet Activation / physiology
  • Platelet Adhesiveness / drug effects
  • Platelet Adhesiveness / physiology
  • Platelet Aggregation* / drug effects
  • Platelet Aggregation* / physiology
  • Thrombin / metabolism
  • Thrombin / pharmacology

Substances

  • Oxidopamine
  • Thrombin