Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease

Autor: Jeremy Camon, Martine Liberge, Lydia Kerkerian-Le Goff, Samira Ztaou, Gaëlle Guiraudie-Capraz, Marianne Amalric, Nicolas Maurice, Corinne Beurrier
Přispěvatelé: Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Dynamique et physiopathologie des réseaux neuronaux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U901), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), ANR-10-BLAN-1416,OptoChAT-Park,Plasticité et rôle des microcircuits striataux impliquant les interneurones cholinergiques dans le fonctionnement physiopathologique des ganglions de la base.(2010), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Khrestchatisky, Michel, BLANC - Plasticité et rôle des microcircuits striataux impliquant les interneurones cholinergiques dans le fonctionnement physiopathologique des ganglions de la base. - - OptoChAT-Park2010 - ANR-10-BLAN-1416 - BLANC - VALID, beurrier, corinne
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
striatum
Parkinson's disease
[SDV]Life Sciences [q-bio]
Striatum
Hypokinesia
Functional Laterality
Levodopa
Mice
0302 clinical medicine
Postsynaptic potential
Transduction
Genetic
Muscarinic acetylcholine receptor
Basal ganglia
cholinergic interneurons
General Neuroscience
Parkinson Disease
Articles
motor symptoms
Cholinergic Neurons
Motor coordination
[SDV] Life Sciences [q-bio]
basal ganglia
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Psychology
medicine.drug
Genotype
Mice
Transgenic
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Medium spiny neuron
Choline O-Acetyltransferase
03 medical and health sciences
Adrenergic Agents
Dopamine
medicine
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Maze Learning
Oxidopamine
Analysis of Variance
muscarinic receptors
Dose-Response Relationship
Drug
Receptor
Muscarinic M4
Receptor
Muscarinic M1
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Corpus Striatum
Mice
Inbred C57BL
Optogenetics
Amphetamine
Disease Models
Animal
Luminescent Proteins
030104 developmental biology
nervous system
Mutation
Exploratory Behavior
Cholinergic
Neuroscience
030217 neurology & neurosurgery
Zdroj: Journal of Neuroscience
Journal of Neuroscience, Society for Neuroscience, 2016, 36 (35), pp.9161-9172. ⟨10.1523/JNEUROSCI.0873-16.2016⟩
Journal of Neuroscience, 2016, 36 (35), pp.9161-9172. ⟨10.1523/JNEUROSCI.0873-16.2016⟩
Journal of Neuroscience, Society for Neuroscience, 2016, 36 (35), pp.9161-72. ⟨10.1523/JNEUROSCI.0873-16.2016.⟩
Journal of Neuroscience, Society for Neuroscience, 2016, ⟨10.1523/JNEUROSCI.0873-16.2016⟩
Journal of Neuroscience, 2016, 36 (35), pp.9161-72. ⟨10.1523/JNEUROSCI.0873-16.2016⟩
ISSN: 0270-6474
1529-2401
Popis: International audience; Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease.SIGNIFICANCE STATEMENT:The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal cholinergic interneurons (ChIs) and muscarinic receptor subtypes (mAChRs) in the occurrence of a wide range of motor deficits such as akinesia, bradykinesia, motor coordination, and sensorimotor neglect after unilateral nigrostriatal 6-hydroxydopamine lesion in mice. Our results show that photoinhibition of ChIs in the dorsal striatum and pharmacological blockade of muscarinic receptors, specifically postsynaptic M1 and M4 mAChRs, alleviate lesion-induced motor deficits. The present study points to these receptor subtypes as potential targets for the symptomatic treatment of parkinsonian-like motor symptoms.
Databáze: OpenAIRE
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