Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease
Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD). Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-08-01
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| Series: | Frontiers in Systems Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00068/full |
| _version_ | 1819067812009738240 |
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| author | Rosa M Villalba Yoland eSmith Yoland eSmith |
| author_facet | Rosa M Villalba Yoland eSmith Yoland eSmith |
| author_sort | Rosa M Villalba |
| collection | DOAJ |
| description | Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD). Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011). The concept of tripartite synapses (TS) was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a). Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD therapeutics. |
| first_indexed | 2024-12-21T16:24:12Z |
| format | Article |
| id | doaj.art-f1b816ad0eab4a25a796eef95e5b8b67 |
| institution | Directory Open Access Journal |
| issn | 1662-5137 |
| language | English |
| last_indexed | 2024-12-21T16:24:12Z |
| publishDate | 2011-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Neuroscience |
| spelling | doaj.art-f1b816ad0eab4a25a796eef95e5b8b672022-12-21T18:57:29ZengFrontiers Media S.A.Frontiers in Systems Neuroscience1662-51372011-08-01510.3389/fnsys.2011.0006811308Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's diseaseRosa M Villalba0Yoland eSmith1Yoland eSmith2Yerkes National Primate Research center, Emory University, Atlanta, GAYerkes National Primate Research center, Emory University, Atlanta, GAEmory UniversityStriatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD). Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011). The concept of tripartite synapses (TS) was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a). Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD therapeutics.http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00068/fullStriatumgliaastrocytenon-human primatescorticostriatalMPTP |
| spellingShingle | Rosa M Villalba Yoland eSmith Yoland eSmith Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease Frontiers in Systems Neuroscience Striatum glia astrocyte non-human primates corticostriatal MPTP |
| title | Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease |
| title_full | Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease |
| title_fullStr | Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease |
| title_full_unstemmed | Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease |
| title_short | Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease |
| title_sort | neuroglial plasticity at striatal glutamatergic synapses in parkinson s disease |
| topic | Striatum glia astrocyte non-human primates corticostriatal MPTP |
| url | http://journal.frontiersin.org/Journal/10.3389/fnsys.2011.00068/full |
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