The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice
Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking func...
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todo:paper_03064522_v99_n4_p643_Murer2023-10-03T15:22:30Z The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice Murer, M.G. Dziewczapolski, G. Salin, P. Vila, M. Tseng, K.Y. Ruberg, M. Rubinstein, M. Kelly, M.A. Grandy, D.K. Low, M.J. Hirsch, E. Raisman-Vozari, R. Gershanik, O. Globus pallidus Parkinson's disease Striatum Substantia nigra Subthalamic nucleus cytochrome c oxidase dopamine 2 receptor glutamate decarboxylase messenger RNA substance P animal tissue article basal ganglion controlled study corpus striatum enzyme activity gene mutation globus pallidus mouse neuromodulation nonhuman Parkinson disease priority journal protein expression receptor gene substantia nigra subthalamic nucleus Animals Electron Transport Complex IV Female Gene Expression Globus Pallidus Glutamate Decarboxylase Male Mice Mice, Inbred C57BL Mice, Knockout Neostriatum Neural Pathways Neurons Parkinson Disease Phenotype Receptors, Dopamine D2 RNA, Messenger Substance P Substantia Nigra Subthalamic Nucleus Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO. Fil:Dziewczapolski, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03064522_v99_n4_p643_Murer |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Globus pallidus Parkinson's disease Striatum Substantia nigra Subthalamic nucleus cytochrome c oxidase dopamine 2 receptor glutamate decarboxylase messenger RNA substance P animal tissue article basal ganglion controlled study corpus striatum enzyme activity gene mutation globus pallidus mouse neuromodulation nonhuman Parkinson disease priority journal protein expression receptor gene substantia nigra subthalamic nucleus Animals Electron Transport Complex IV Female Gene Expression Globus Pallidus Glutamate Decarboxylase Male Mice Mice, Inbred C57BL Mice, Knockout Neostriatum Neural Pathways Neurons Parkinson Disease Phenotype Receptors, Dopamine D2 RNA, Messenger Substance P Substantia Nigra Subthalamic Nucleus |
| spellingShingle |
Globus pallidus Parkinson's disease Striatum Substantia nigra Subthalamic nucleus cytochrome c oxidase dopamine 2 receptor glutamate decarboxylase messenger RNA substance P animal tissue article basal ganglion controlled study corpus striatum enzyme activity gene mutation globus pallidus mouse neuromodulation nonhuman Parkinson disease priority journal protein expression receptor gene substantia nigra subthalamic nucleus Animals Electron Transport Complex IV Female Gene Expression Globus Pallidus Glutamate Decarboxylase Male Mice Mice, Inbred C57BL Mice, Knockout Neostriatum Neural Pathways Neurons Parkinson Disease Phenotype Receptors, Dopamine D2 RNA, Messenger Substance P Substantia Nigra Subthalamic Nucleus Murer, M.G. Dziewczapolski, G. Salin, P. Vila, M. Tseng, K.Y. Ruberg, M. Rubinstein, M. Kelly, M.A. Grandy, D.K. Low, M.J. Hirsch, E. Raisman-Vozari, R. Gershanik, O. The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| topic_facet |
Globus pallidus Parkinson's disease Striatum Substantia nigra Subthalamic nucleus cytochrome c oxidase dopamine 2 receptor glutamate decarboxylase messenger RNA substance P animal tissue article basal ganglion controlled study corpus striatum enzyme activity gene mutation globus pallidus mouse neuromodulation nonhuman Parkinson disease priority journal protein expression receptor gene substantia nigra subthalamic nucleus Animals Electron Transport Complex IV Female Gene Expression Globus Pallidus Glutamate Decarboxylase Male Mice Mice, Inbred C57BL Mice, Knockout Neostriatum Neural Pathways Neurons Parkinson Disease Phenotype Receptors, Dopamine D2 RNA, Messenger Substance P Substantia Nigra Subthalamic Nucleus |
| description |
Recent pathophysiological models of basal ganglia function in Parkinson's disease predict that specific neurochemical changes in the indirect pathway would follow the lack of stimulation of D2 dopamine receptors. Post mortem studies of the basal ganglia in genetically modified mice lacking functional copies of the D2 dopamine receptor gene allowed us to test these predictions. When compared with their congenic N5 wild-type siblings, mice lacking D2 receptors show an increased expression of enkephalin messenger RNA in the striatum, and an increased activity and expression of cytochrome oxidase I in the subthalamic nucleus, as expected. In addition, D2 receptor-deficient mice display a reduced expression of glutamate decarboxylase-67 messenger RNA in the globus pallidus, as the basal ganglia model predicts. This reduction contrasts with the lack of change or increase in glutamate decarboxylase-67 messenger RNA expression found in animals depleted of dopamine after lesions of the mesostriatal dopaminergic system. Furthermore, D2 receptor-deficient mice show a significant decrease in substance P messenger RNA expression in the striatonigral neurons which form the direct pathway. Finally, glutamate decarboxylase-67 messenger RNA expression in the basal ganglia output nuclei was not affected by mutations in the D2 receptor gene, a fact that could probably be related to the absence of a parkinsonian locomotor phenotype in D2 receptor-deficient mice. In summary, these findings provide compelling evidence demonstrating that the lack of endogenous stimulation of D2 receptors is sufficient to produce subthalamic nucleus hyperactivity, as assessed by cytochrome oxidase I histochemistry and messenger RNA expression, and strongly suggest the existence of interactions between the basal ganglia direct and indirect pathways. (C) 2000 IBRO. |
| format |
JOUR |
| author |
Murer, M.G. Dziewczapolski, G. Salin, P. Vila, M. Tseng, K.Y. Ruberg, M. Rubinstein, M. Kelly, M.A. Grandy, D.K. Low, M.J. Hirsch, E. Raisman-Vozari, R. Gershanik, O. |
| author_facet |
Murer, M.G. Dziewczapolski, G. Salin, P. Vila, M. Tseng, K.Y. Ruberg, M. Rubinstein, M. Kelly, M.A. Grandy, D.K. Low, M.J. Hirsch, E. Raisman-Vozari, R. Gershanik, O. |
| author_sort |
Murer, M.G. |
| title |
The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| title_short |
The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| title_full |
The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| title_fullStr |
The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| title_full_unstemmed |
The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice |
| title_sort |
indirect basal ganglia pathway in dopamine d2 receptor-deficient mice |
| url |
http://hdl.handle.net/20.500.12110/paper_03064522_v99_n4_p643_Murer |
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1807317705046360064 |