Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum
L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators o...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2015/253878 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552587816075264 |
|---|---|
| author | Huan Du Shuke Nie Guiqin Chen Kai Ma Yan Xu Zhentao Zhang Stella M. Papa Xuebing Cao |
| author_facet | Huan Du Shuke Nie Guiqin Chen Kai Ma Yan Xu Zhentao Zhang Stella M. Papa Xuebing Cao |
| author_sort | Huan Du |
| collection | DOAJ |
| description | L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression of ΔFosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies. |
| format | Article |
| id | doaj-art-b379a3972bf543e292897877768a0d63 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-b379a3972bf543e292897877768a0d632025-02-03T05:58:20ZengWileyParkinson's Disease2090-80832042-00802015-01-01201510.1155/2015/253878253878Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the StriatumHuan Du0Shuke Nie1Guiqin Chen2Kai Ma3Yan Xu4Zhentao Zhang5Stella M. Papa6Xuebing Cao7Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaDepartment of Neurology, Renmin Hospital, Wuhan University, Wuhan 430060, ChinaYerkes National Primate Research Center, Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USADepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, ChinaL-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression of ΔFosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies.http://dx.doi.org/10.1155/2015/253878 |
| spellingShingle | Huan Du Shuke Nie Guiqin Chen Kai Ma Yan Xu Zhentao Zhang Stella M. Papa Xuebing Cao Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum Parkinson's Disease |
| title | Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum |
| title_full | Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum |
| title_fullStr | Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum |
| title_full_unstemmed | Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum |
| title_short | Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum |
| title_sort | levetiracetam ameliorates l dopa induced dyskinesia in hemiparkinsonian rats inducing critical molecular changes in the striatum |
| url | http://dx.doi.org/10.1155/2015/253878 |
| work_keys_str_mv | AT huandu levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT shukenie levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT guiqinchen levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT kaima levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT yanxu levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT zhentaozhang levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT stellampapa levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum AT xuebingcao levetiracetamamelioratesldopainduceddyskinesiainhemiparkinsonianratsinducingcriticalmolecularchangesinthestriatum |