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A2A receptor knockout worsens survival and motor behaviour in a transgenic mouse model of Huntington's disease.
Neurobiol Dis. 2011 Feb; 41(2):570-6.ND

Abstract

Huntington's disease (HD) is a progressive neurodegenerative genetic disorder that leads to motor, cognitive, and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. HD preferentially affects efferent striato-pallidal neurons that express enkephalin as well as dopamine D2 and A(2A) adenosine receptors (A(2A)Rs). Expression and function of A(2A)Rs are altered in HD but, despite being an important modulator of the striato-pallidal function, the subsequent pathophysiological consequence of such changes remains unclear. Whether blockade of A(2A)Rs is of therapeutic interest in HD remains ill-defined. In the present work, we aimed to determine the pathophysiological consequences of genetic deletion of A(2A)Rs in HD by crossing A(2A)R knockout mice with the N171-82Q HD transgenic model. Our data demonstrate that knockout of A(2A)Rs moderately but significantly worsens motor performances and survival of N171-82Q mice and leads to a decrease in striatal enkephalin expression. These results support that early and chronic blockade of A(2A)Rs might not be beneficial in HD.

Authors+Show Affiliations

IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21062644

Citation

Mievis, Stéphane, et al. "A2A Receptor Knockout Worsens Survival and Motor Behaviour in a Transgenic Mouse Model of Huntington's Disease." Neurobiology of Disease, vol. 41, no. 2, 2011, pp. 570-6.
Mievis S, Blum D, Ledent C. A2A receptor knockout worsens survival and motor behaviour in a transgenic mouse model of Huntington's disease. Neurobiol Dis. 2011;41(2):570-6.
Mievis, S., Blum, D., & Ledent, C. (2011). A2A receptor knockout worsens survival and motor behaviour in a transgenic mouse model of Huntington's disease. Neurobiology of Disease, 41(2), 570-6. https://doi.org/10.1016/j.nbd.2010.09.021
Mievis S, Blum D, Ledent C. A2A Receptor Knockout Worsens Survival and Motor Behaviour in a Transgenic Mouse Model of Huntington's Disease. Neurobiol Dis. 2011;41(2):570-6. PubMed PMID: 21062644.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A2A receptor knockout worsens survival and motor behaviour in a transgenic mouse model of Huntington's disease. AU - Mievis,Stéphane, AU - Blum,David, AU - Ledent,Catherine, Y1 - 2010/11/06/ PY - 2010/06/30/received PY - 2010/09/19/revised PY - 2010/09/23/accepted PY - 2010/11/11/entrez PY - 2010/11/11/pubmed PY - 2011/12/13/medline SP - 570 EP - 6 JF - Neurobiology of disease JO - Neurobiol Dis VL - 41 IS - 2 N2 - Huntington's disease (HD) is a progressive neurodegenerative genetic disorder that leads to motor, cognitive, and psychiatric disturbances. The primary neuropathological hallmark is atrophy of the striatum. HD preferentially affects efferent striato-pallidal neurons that express enkephalin as well as dopamine D2 and A(2A) adenosine receptors (A(2A)Rs). Expression and function of A(2A)Rs are altered in HD but, despite being an important modulator of the striato-pallidal function, the subsequent pathophysiological consequence of such changes remains unclear. Whether blockade of A(2A)Rs is of therapeutic interest in HD remains ill-defined. In the present work, we aimed to determine the pathophysiological consequences of genetic deletion of A(2A)Rs in HD by crossing A(2A)R knockout mice with the N171-82Q HD transgenic model. Our data demonstrate that knockout of A(2A)Rs moderately but significantly worsens motor performances and survival of N171-82Q mice and leads to a decrease in striatal enkephalin expression. These results support that early and chronic blockade of A(2A)Rs might not be beneficial in HD. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/21062644/A2A_receptor_knockout_worsens_survival_and_motor_behaviour_in_a_transgenic_mouse_model_of_Huntington's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(10)00372-4 DB - PRIME DP - Unbound Medicine ER -