Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

Ross B Mounsey, Sarah Mustafa, Lianne Robinson, Ruth A. Ross, Gernot Riedel, Roger G. Pertwee, Peter Teismann*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)
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Abstract

Parkinson's disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain. Symptomatic therapies are available but no treatment slows or prevents the loss of neurons. Neuroinflammation has been implicated in its pathogenesis. To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients. Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated. The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5 mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death. Furthermore, the addition of DFU (25 mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects. Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits. The results expand the current understanding of the role that this signalling system has and its potential influence in PD.
Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalExperimental Neurology
Volume273
Early online date2 Aug 2015
DOIs
Publication statusPublished - Nov 2015

Keywords

  • Endocannabinoids
  • Parkinson's disease
  • MPTP
  • Neuroprotection
  • CB1 cannabinoid receptors
  • toxicity in-vivo
  • monoacylglycerol lipase
  • Huntingtons-Disease
  • cerebrospinal-fluid
  • Alzheimers-Disease
  • induced neurotoxicity
  • up-regulation
  • factor-alpha
  • brain

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