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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Autores principales:	Dziewczapolski, Gustavo, Rubinstein, Marcelo
Publicado:	2000
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v99_n4_p643_Murer http://hdl.handle.net/20.500.12110/paper_03064522_v99_n4_p643_Murer
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_03064522_v99_n4_p643_Murer2023-06-08T15:31:20Z The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice Dziewczapolski, Gustavo Rubinstein, Marcelo 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. 2000 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v99_n4_p643_Murer 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 Dziewczapolski, Gustavo Rubinstein, Marcelo 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.
author	Dziewczapolski, Gustavo Rubinstein, Marcelo
author_facet	Dziewczapolski, Gustavo Rubinstein, Marcelo
author_sort	Dziewczapolski, Gustavo
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
publishDate	2000
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v99_n4_p643_Murer http://hdl.handle.net/20.500.12110/paper_03064522_v99_n4_p643_Murer
work_keys_str_mv	AT dziewczapolskigustavo theindirectbasalgangliapathwayindopamined2receptordeficientmice AT rubinsteinmarcelo theindirectbasalgangliapathwayindopamined2receptordeficientmice AT dziewczapolskigustavo indirectbasalgangliapathwayindopamined2receptordeficientmice AT rubinsteinmarcelo indirectbasalgangliapathwayindopamined2receptordeficientmice
_version_	1768543659081334784

The indirect basal ganglia pathway in dopamine D2 receptor-deficient mice

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