Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats
Dopamine (DA) depletion in the nigrostriatal system leads to basal ganglia dysfunction both in Parkinson's disease (PD) and in 6-hydroxy dopamine (6-OHDA)-lesioned rats with neuronal hyperactivity in the subthalamic nucleus (STN), i.e. increased firing rate and burst activity, together with enh...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-11-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113002179 |
| _version_ | 1818350589515399168 |
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| author | Regina Rumpel Mesbah Alam Alexander Klein Meltem Özer Maike Wesemann Xingxing Jin Joachim K. Krauss Kerstin Schwabe Andreas Ratzka Claudia Grothe |
| author_facet | Regina Rumpel Mesbah Alam Alexander Klein Meltem Özer Maike Wesemann Xingxing Jin Joachim K. Krauss Kerstin Schwabe Andreas Ratzka Claudia Grothe |
| author_sort | Regina Rumpel |
| collection | DOAJ |
| description | Dopamine (DA) depletion in the nigrostriatal system leads to basal ganglia dysfunction both in Parkinson's disease (PD) and in 6-hydroxy dopamine (6-OHDA)-lesioned rats with neuronal hyperactivity in the subthalamic nucleus (STN), i.e. increased firing rate and burst activity, together with enhanced beta oscillatory activity. Moreover, intrastriatal transplantation of DA neurons has been shown to functionally re-innervate the host striatum and restore DA input.However, the effects of those transplanted cells on the STN are not well characterized. Therefore, we transplanted cells, derived from the ventral mesencephalon of E12 rat embryos, intrastriatally in the unilateral 6-OHDA-lesioned rat model of PD. We combined behavioral and histological findings with electrophysiological extracellular recordings in the STN, as well as qRT-PCR analyses of dopaminergic, GABAergic, and glutamatergic transporter and receptor genes in the striatum and the STN. Transplanted animals displayed improved rotational behavior after amphetamine injection by 50% in rats with small grafts (586 ± 109 SEM dopamine cells), or even overcompensation by 116% in rats with large grafts (3486 ± 548 SEM dopamine cells). Electrophysiological measurements revealed, that in rats with large grafts burst activity was not affected, while STN neuronal firing rate, as well as beta oscillatory activity was alleviated, whereas small grafts had less impact. Interestingly, both behavioral and electrophysiological measures were dependent on the number of surviving tyrosine hydroxylase positive cells. Although grafted rats displayed restored expression of the GABA synthesizing enzymes Gad65 and Gad67 in the striatum compared to naive rats, the grafts induced a decreased mRNA expression of dopamine receptor Drd2, glutamate receptors AMPA3, NMDA2A, and NMDA2B, and glutamate transporter Eaat3. Interestingly, the NMDA receptor subunit 2B and glutamate transporter Eaat3 were also less expressed in the STN of grafted animals compared to naive rats.In summary, DA grafts restore functional deficits and cause partial improvement of subthalamic neuronal activity. Incomplete recovery, however, may be due to decreased receptor gene expression induced by DA grafts in the striatum and in the STN. |
| first_indexed | 2024-12-13T18:24:15Z |
| format | Article |
| id | doaj.art-d028ba46bcbc42d89629d5ac27a8d7b3 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T18:24:15Z |
| publishDate | 2013-11-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-d028ba46bcbc42d89629d5ac27a8d7b32022-12-21T23:35:38ZengElsevierNeurobiology of Disease1095-953X2013-11-0159230243Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian ratsRegina Rumpel0Mesbah Alam1Alexander Klein2Meltem Özer3Maike Wesemann4Xingxing Jin5Joachim K. Krauss6Kerstin Schwabe7Andreas Ratzka8Claudia Grothe9Institute of Neuroanatomy, Hannover Medical School, Hannover, GermanyDepartment of Neurosurgery, Hannover Medical School, Hannover, GermanyInstitute of Neuroanatomy, Hannover Medical School, Hannover, GermanyInstitute of Neuroanatomy, Hannover Medical School, Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Hannover, GermanyInstitute of Neuroanatomy, Hannover Medical School, Hannover, GermanyDepartment of Neurosurgery, Hannover Medical School, Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Hannover, GermanyDepartment of Neurosurgery, Hannover Medical School, Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Hannover, GermanyDepartment of Neurosurgery, Hannover Medical School, Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Hannover, GermanyInstitute of Neuroanatomy, Hannover Medical School, Hannover, GermanyInstitute of Neuroanatomy, Hannover Medical School, Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Hannover, Germany; Corresponding author at: Hannover Medical School, Institute of Neuroanatomy (OE4140), Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Fax: +49 511 532 2880.Dopamine (DA) depletion in the nigrostriatal system leads to basal ganglia dysfunction both in Parkinson's disease (PD) and in 6-hydroxy dopamine (6-OHDA)-lesioned rats with neuronal hyperactivity in the subthalamic nucleus (STN), i.e. increased firing rate and burst activity, together with enhanced beta oscillatory activity. Moreover, intrastriatal transplantation of DA neurons has been shown to functionally re-innervate the host striatum and restore DA input.However, the effects of those transplanted cells on the STN are not well characterized. Therefore, we transplanted cells, derived from the ventral mesencephalon of E12 rat embryos, intrastriatally in the unilateral 6-OHDA-lesioned rat model of PD. We combined behavioral and histological findings with electrophysiological extracellular recordings in the STN, as well as qRT-PCR analyses of dopaminergic, GABAergic, and glutamatergic transporter and receptor genes in the striatum and the STN. Transplanted animals displayed improved rotational behavior after amphetamine injection by 50% in rats with small grafts (586 ± 109 SEM dopamine cells), or even overcompensation by 116% in rats with large grafts (3486 ± 548 SEM dopamine cells). Electrophysiological measurements revealed, that in rats with large grafts burst activity was not affected, while STN neuronal firing rate, as well as beta oscillatory activity was alleviated, whereas small grafts had less impact. Interestingly, both behavioral and electrophysiological measures were dependent on the number of surviving tyrosine hydroxylase positive cells. Although grafted rats displayed restored expression of the GABA synthesizing enzymes Gad65 and Gad67 in the striatum compared to naive rats, the grafts induced a decreased mRNA expression of dopamine receptor Drd2, glutamate receptors AMPA3, NMDA2A, and NMDA2B, and glutamate transporter Eaat3. Interestingly, the NMDA receptor subunit 2B and glutamate transporter Eaat3 were also less expressed in the STN of grafted animals compared to naive rats.In summary, DA grafts restore functional deficits and cause partial improvement of subthalamic neuronal activity. Incomplete recovery, however, may be due to decreased receptor gene expression induced by DA grafts in the striatum and in the STN.http://www.sciencedirect.com/science/article/pii/S0969996113002179TransplantationBrain repairEmbryonic tissueDrug-induced rotation6-OHDART-PCR |
| spellingShingle | Regina Rumpel Mesbah Alam Alexander Klein Meltem Özer Maike Wesemann Xingxing Jin Joachim K. Krauss Kerstin Schwabe Andreas Ratzka Claudia Grothe Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats Neurobiology of Disease Transplantation Brain repair Embryonic tissue Drug-induced rotation 6-OHDA RT-PCR |
| title | Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| title_full | Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| title_fullStr | Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| title_full_unstemmed | Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| title_short | Neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| title_sort | neuronal firing activity and gene expression changes in the subthalamic nucleus after transplantation of dopamine neurons in hemiparkinsonian rats |
| topic | Transplantation Brain repair Embryonic tissue Drug-induced rotation 6-OHDA RT-PCR |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113002179 |
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