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Worsening of Huntington disease phenotype in CB1 receptor knockout mice.

Abstract

Huntington's disease (HD) is a progressive neurodegenerative genetic disorder which leads to motor, cognitive and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. Cannabinoid CB1 receptors (CB1Rs) are particularly enriched in the striatum and previous works indicate their early loss of expression in HD, even before symptom occurrence. However, pathophysiological significance of this loss of expression remains unclear. In addition, whether specific modulation of CB1R is able to mitigate striatal neuron fate in HD remains currently controversial. In order to gain further insights on the potential role of CB1R in HD physiopathology, we evaluated the pathophysiological consequences of a genetic deletion of CB1R in the N171-82Q transgenic model and following 3-nitropropionic (3NP) intoxication. Taken together our data demonstrate that CB1R knockout (1) worsens motor performances in N171-82Q mice and (2) increases mouse susceptibility to 3NP. These results suggest that functional changes in CB1R may contribute to the physiopathological development of HD.

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  • Authors+Show Affiliations

    ,

    IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.

    ,

    Source

    Neurobiology of disease 42:3 2011 Jun pg 524-9

    MeSH

    Analysis of Variance
    Animals
    Corpus Striatum
    Disease Models, Animal
    Disease Progression
    Female
    Huntington Disease
    Male
    Mice
    Mice, Knockout
    Motor Activity
    Neurons
    Nitro Compounds
    Phenotype
    Propionates
    Receptor, Cannabinoid, CB1
    Rotarod Performance Test

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21406230

    Citation

    Mievis, Stéphane, et al. "Worsening of Huntington Disease Phenotype in CB1 Receptor Knockout Mice." Neurobiology of Disease, vol. 42, no. 3, 2011, pp. 524-9.
    Mievis S, Blum D, Ledent C. Worsening of Huntington disease phenotype in CB1 receptor knockout mice. Neurobiol Dis. 2011;42(3):524-9.
    Mievis, S., Blum, D., & Ledent, C. (2011). Worsening of Huntington disease phenotype in CB1 receptor knockout mice. Neurobiology of Disease, 42(3), pp. 524-9. doi:10.1016/j.nbd.2011.03.006.
    Mievis S, Blum D, Ledent C. Worsening of Huntington Disease Phenotype in CB1 Receptor Knockout Mice. Neurobiol Dis. 2011;42(3):524-9. PubMed PMID: 21406230.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Worsening of Huntington disease phenotype in CB1 receptor knockout mice. AU - Mievis,Stéphane, AU - Blum,David, AU - Ledent,Catherine, Y1 - 2011/03/22/ PY - 2010/11/04/received PY - 2011/02/15/revised PY - 2011/03/06/accepted PY - 2011/3/17/entrez PY - 2011/3/17/pubmed PY - 2011/8/24/medline SP - 524 EP - 9 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 42 IS - 3 N2 - Huntington's disease (HD) is a progressive neurodegenerative genetic disorder which leads to motor, cognitive and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. Cannabinoid CB1 receptors (CB1Rs) are particularly enriched in the striatum and previous works indicate their early loss of expression in HD, even before symptom occurrence. However, pathophysiological significance of this loss of expression remains unclear. In addition, whether specific modulation of CB1R is able to mitigate striatal neuron fate in HD remains currently controversial. In order to gain further insights on the potential role of CB1R in HD physiopathology, we evaluated the pathophysiological consequences of a genetic deletion of CB1R in the N171-82Q transgenic model and following 3-nitropropionic (3NP) intoxication. Taken together our data demonstrate that CB1R knockout (1) worsens motor performances in N171-82Q mice and (2) increases mouse susceptibility to 3NP. These results suggest that functional changes in CB1R may contribute to the physiopathological development of HD. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/21406230/abstract/Worsening_of_Huntington_disease_phenotype_in_CB1_receptor_knockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(11)00088-X DB - PRIME DP - Unbound Medicine ER -