Time-Course of Alterations in the Endocannabinoid System after Viral-Mediated Overexpression of α-Synuclein in the Rat Brain.


Journal

Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009

Informations de publication

Date de publication:
14 Jan 2022
Historique:
received: 17 12 2021
revised: 06 01 2022
accepted: 12 01 2022
entrez: 21 1 2022
pubmed: 22 1 2022
medline: 17 2 2022
Statut: epublish

Résumé

Since the discovery of α-synuclein as the major component in Lewy bodies, research into this protein in the context of Parkinson's disease pathology has been exponential. Cannabinoids are being investigated as potential therapies for Parkinson's disease from numerous aspects, but still little is known about the links between the cannabinoid system and the pathogenic α-synuclein protein; understanding these links will be necessary if cannabinoid therapies are to reach the clinic in the future. Therefore, the aim of this study was to investigate the time-course of alterations in components of the endocannabinoid system after viral-mediated α-synuclein overexpression in the rat brain. Rats were given unilateral intranigral injections of AAV-GFP or AAV-α-synuclein and sacrificed 4, 8 and 12 weeks later for qRT-PCR and liquid chromatography-mass spectrometry analyses of the endocannabinoid system, in addition to histological visualization of α-synuclein expression along the nigrostriatal pathway. As anticipated, intranigral delivery of AAV-α-synuclein induced widespread overexpression of human α-synuclein in the nigrostriatal pathway, both at the mRNA level and the protein level. However, despite this profound α-synuclein overexpression, we detected no differences in CB

Identifiants

pubmed: 35056822
pii: molecules27020507
doi: 10.3390/molecules27020507
pmc: PMC8778740
pii:
doi:

Substances chimiques

Endocannabinoids 0
Receptor, Cannabinoid, CB1 0
Receptor, Cannabinoid, CB2 0
SNCA protein, human 0
alpha-Synuclein 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Irish Research Council
ID : GOIPG/2018/71
Organisme : Hardiman Scholarships
ID : N/A

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Auteurs

Rachel Kelly (R)

Department of Pharmacology & Therapeutics and Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland.

Alexis-Pierre Bemelmans (AP)

Neurodegenerative Diseases Laboratory, Molecular Imaging Research Center, Paris-Saclay University, CEA, CNRS, F-92265 Fontenay-aux-Roses, France.

Charlène Joséphine (C)

Neurodegenerative Diseases Laboratory, Molecular Imaging Research Center, Paris-Saclay University, CEA, CNRS, F-92265 Fontenay-aux-Roses, France.

Emmanuel Brouillet (E)

Neurodegenerative Diseases Laboratory, Molecular Imaging Research Center, Paris-Saclay University, CEA, CNRS, F-92265 Fontenay-aux-Roses, France.

Declan P McKernan (DP)

Department of Pharmacology & Therapeutics and Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland.

Eilís Dowd (E)

Department of Pharmacology & Therapeutics and Galway Neuroscience Centre, National University of Ireland Galway, H91 W5P7 Galway, Ireland.

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Classifications MeSH