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Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism

التفاصيل البيبلوغرافية
العنوان: Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism
المؤلفون: E P Bello, R Casas-Cordero, Mariano A. Belluscio, Vanina Rodriguez, Gregorio L. Galiñanes, Eric Casey, M Rubinstein, Daniela Noain, Mario Gustavo Murer
بيانات النشر: Nature Publishing Group, 2016.
سنة النشر: 2016
مصطلحات موضوعية: Ablation Techniques, Male, 0301 basic medicine, CIENCIAS MÉDICAS Y DE LA SALUD, Dopamine, Neurociencias, Stimulation, Motor Activity, Basal Ganglia, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Parkinsonian Disorders, Basal ganglia, medicine, Animals, Humans, Learning, Molecular Biology, Motor skill, Mice, Knockout, Receptors, Dopamine D2, Receptors, Dopamine D1, Parkinsonism, medicine.disease, Corpus Striatum, Motor coordination, Parkinson'S Disease, Psychiatry and Mental health, Medicina Básica, 030104 developmental biology, Motor Skills, Schizophrenia, Dopamine Antagonists, Motor learning, Psychology, Neuroscience, Locomotion, 030217 neurology & neurosurgery, medicine.drug
الوصف: Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function. In this study, we generated an inducible Drd2 null-allele mouse strain that circumvented developmental compensations found in constitutive Drd2−/− mice and allowed us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning. We have found that loss of D2R during adulthood causes severe motor impairments, including hypolocomotion, deficits in motor coordination, impaired learning of new motor routines and spontaneous catatonia. Moreover, severe motor impairment, resting tremor and abnormal gait and posture, phenotypes reminiscent of Parkinson’s disease, were evident when the mutation was induced in aged mice. Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette’s syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder. Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Casas Cordero, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Galiñanes, Gregorio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Casey, Eric. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Rodríguez, V. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina Fil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ; Argentina
وصف الملف: application/pdf
اللغة: English
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91ef22ae615896bddb45a9d711d1fc91
https://www.nature.com/articles/mp2016105
Rights: RESTRICTED
رقم الانضمام: edsair.doi.dedup.....91ef22ae615896bddb45a9d711d1fc91
قاعدة البيانات: OpenAIRE
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