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Published on: January 8, 2015
Alteration of the endocannabinoid system in mouse brain during prion disease
S Petrosino1, B Ménard, N Zsürger
1Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR Via Campi Flegrei 34, Comprensorio Olivetti, 80078 Pozzuoli (NA), Italy.
Abstract:
Prion diseases are neurodegenerative disorders characterized by deposition of the pathological prion protein (PrPsc) within the brain of affected humans and animals. Microglial cell activation is a common feature of prion diseases; alterations of various neurotransmitter systems and neurotransmission have been also reported. Owing to its ability to modulate both neuroimmune responses and neurotransmission, it was of interest to study the brain endocannabinoid system in a prion-infected mouse model. The production of the endocannabinoid, 2-arachidonoyglycerol (2-AG), was enhanced 10 weeks post-infection, without alteration of the other endocannabinoid, anandamide. The CB2 receptor expression was up-regulated in brains of prion-infected mice as early as 10 weeks and up to 32 weeks post-infection whereas the mRNAs of other cannabinoid receptors (CBRs) remain unchanged. The observed alterations of the endocannabinoid system were specific for prion infection since no significant changes were observed in the brain of prion-resistant mice, that is, mice devoid of the Prnp gene. Our study highlights important alterations of the endocannabinoid system during early stages of the disease long before the clinical signs of the disease.
Insights
Prion diseases alter the brain endocannabinoid system early in infection. Researchers found increased 2-arachidonoylglycerol (2-AG) and CB2 receptor expression in prion-infected mice before clinical signs emerge.
Area of Science:
- Neuroscience
- Neuroimmunology
- Molecular Biology
Background:
- Prion diseases are fatal neurodegenerative conditions.
- Microglial activation and neurotransmitter system changes are common in prion diseases.
- The endocannabinoid system's role in prion disease is largely unknown.
Purpose of the Study:
- To investigate alterations in the brain endocannabinoid system during prion infection.
- To determine if the endocannabinoid system is affected before clinical prion disease symptoms appear.
Main Methods:
- Utilized a prion-infected mouse model.
- Measured levels of endocannabinoids (anandamide, 2-arachidonoylglycerol) and cannabinoid receptor (CB1, CB2) expression.
- Compared prion-infected mice with prion-resistant mice (Prnp gene knockout).
Main Results:
- Elevated 2-arachidonoylglycerol (2-AG) production was observed 10 weeks post-infection.
- CB2 receptor expression significantly increased in prion-infected mice from 10 to 32 weeks post-infection.
- No significant changes were found in prion-resistant mice, indicating specificity to prion infection.
Conclusions:
- The endocannabinoid system is significantly altered during the early, preclinical stages of prion disease.
- Upregulation of CB2 receptors and increased 2-AG suggest a potential role in neuroimmune modulation during prion pathogenesis.
- These findings highlight the endocannabinoid system as a potential therapeutic target for prion diseases.
