Differential expression of FosB, c-Fos, and Zif268 in forebrain regions after acute or chronic l-DOPA treatment in a rat model of Parkinson's disease

Ebihara, Kosuke; Ishida, Yoshiteru; Takeda, Ryuichiro; Abe, Hiroshi; Matsuo, Hitoshi; Kawai, Keiichi; Magata, Yasuhiro; Nishimori, Toshikazu

doi:10.1016/j.neulet.2011.03.087

Cited by 13 publications

(15 citation statements)

References 26 publications

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“…For instance, L-dopa treatment induces c-Fos expression in striatum by activation of both D1 and D2 receptors (Ebihara et al, 2011; Paul et al, 1992; Robertson et al, 1989). In the current study, we focused on the dorsolateral striatum because the most pronounced effect is observed in this region (Bishop et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent optical activation of cholinergic interneurons may provide a further stimulus for the expression of LIDs because of activation/inactivation of some common molecular mechanism. For instance, earlier work has demonstrated changes in c-Fos expression with the occurrence of LIDs (Bishop et al, 2009; Ebihara et al, 2011; Paul et al, 1992; Robertson et al, 1989). The current work shows that optical stimulation of cholinergic neurons is also associated with alterations in c-Fos expressing striatal neurons.…”

Section: Discussionmentioning

confidence: 99%

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Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Bordia

Perez

Heiss

et al. 2016

Neurobiology of Disease

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L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson's disease. Emerging evidence indicates that the nicotinic cholinergic system plays a role in LIDs, although the pathways and mechanisms are poorly understood. Here we used optogenetics to investigate the role of striatal cholinergic interneurons in LIDs. Mice expressing cre-recombinase under the control of the choline acetyltransferase promoter (ChAT-Cre) were lesioned by unilateral injection of 6-hydroxydopamine. AAV5-ChR2-eYFP or AAV5-control-eYFP was injected into the dorsolateral striatum, and optical fibers implanted. After stable virus expression, mice were treated with L-dopa. They were then subjected to various stimulation protocols for 2 h and LIDs rated. Continuous stimulation with a short duration optical pulse (1-5 ms) enhanced LIDs. This effect was blocked by the general muscarinic acetylcholine receptor (mAChR) antagonist atropine indicating it was mAChR-mediated. By contrast, continuous stimulation with a longer duration optical pulse (20 ms to 1 s) reduced LIDs to a similar extent as nicotine treatment (~50%). The general nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the decline in LIDs with longer optical pulses showing it was nAChR-mediated. None of the stimulation regimens altered LIDs in control-eYFP mice. Lesion-induced motor impairment was not affected by optical stimulation indicating that cholinergic transmission selectively regulates LIDs. Longer pulse stimulation increased the number of c-Fos expressing ChAT neurons, suggesting that changes in this immediate early gene may be involved. These results demonstrate that striatal cholinergic interneurons play a critical role in LIDs and support the idea that nicotine treatment reduces LIDs via nAChR desensitization.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Bordia

Perez

Heiss

et al. 2016

Neurobiology of Disease

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“…26,28) We also confirmed the induction of AIMs by repeated L-DOPA treatment in 6-OHDA-lesioned rats in the present and previous studies. 13) This induction may be due to the facilitation of neurotransmission of DA synthesized from exogenous L-DOPA in the unilateral DA-depleted striatum by 6-OHDA; in the striatum on the lesion side, DA was synthesized in 5-HT neurons instead of DA neurons because 5-HT neurons contain AADC, an enzyme for DA synthesis. 19,20,36) This neural mechanism was supported by the presence of a nearly normal number of 5-HT immunoreactive nerve terminals in the DA-depleted striatum, as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The dose of YKS (1 g/kg) in the present study was determined according to the results of our previous studies, in which treatment with 1 g/ kg of YKS significantly ameliorated aggressiveness, impaired sociality, or anxiety in animal models of neuropsychiatric disorders. [8][9][10]30) AIMs were evaluated as described previously 13,31) with modifications. The rats in each group were observed for 1 min every 10 min for 180 min after the injection of L-DOPA.…”

Section: Methodsmentioning

confidence: 99%

“…The 6-OHDA-lesioned rat model of PD has been instrumental in studies using various approaches to investigate L-DOPA-induced plasticity at multiple levels. 13) For example, motor complications induced by repeated L-DOPA treatment were manifested as abnormal involuntary movements (AIMs), which included a contralateral rotational response, in 6-OHDA-lesioned rats. 14,15) The development of AIMs has been attributed, in part, to a compensating mechanism of DA conversion from exogenous L-DOPA in serotonergic fibers of the DA-depleted striatum by 6-OHDA [16][17][18] ; aromatic amino acid decarboxylase (AADC) contained in DA and serotonin (5-HT) neurons synthesizes DA and 5-HT from L-DOPA and 5-hydroxy-L-tryptophan (5-HTP), respectively.…”

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confidence: 99%

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Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Ishida

Ebihara

Tabuchi

et al. 2016

Biological & Pharmaceutical Bulletin

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The aim of the present study was to investigate the effects of the traditional Japanese medicine yokukansan (YKS) on the function of dopamine (DA) in the rat nigrostriatal system. Unilateral 6-hydroxydopamine lesions were produced in the rat nigrostriatal system. Despite a marked loss in the striatal immunoreactivity of tyrosine hydroxylase on the lesion side, striatal serotonin (5-HT) immunoreactivity was not affected. Treatment using L-3,4-dihydroxyphenylalanine (L-DOPA) in conjunction with benserazide for 15 d induced abnormal involuntary movements (AIMs) such as locomotive (rotational response), axial, forelimb, and orolingual movements in the lesioned rats. The L-DOPA-induced locomotive and axial, but not forelimb and orolingual, AIMs were significantly increased and prolonged by the pre-administration of YKS. We next investigated

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Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics

2014

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For all its imperfections at treating Parkinson's disease (PD), orally-administered levodopa (l-dopa) can be regarded as the "platinum" standard of PD therapeutics for its impact on disability and discomfort and its cost-effectiveness. The past half-century has confirmed that the typical l-dopa-treated patient gains improvement for most Parkinsonian features, presumably by conversion of this amino acid into dopamine in the striatum. However, fundamental questions remain as to its full mechanism of action and how adverse reactions evolve. Various aspects of clinical phenomenology associated with chronic l-dopa use (such as dyskinesias and the long-duration anti-Parkinsonian response) present a continuing challenge for better understanding of its pharmacology. The pharmacokinetics of l-dopa tend to predict some of problems that can emerge during chronic therapy, which can be linked with its irregular uptake and marked dose-by-dose variability in plasma concentrations. Several new pharmaceutical approaches are targeted at the unique physiology of l-dopa uptake and are likely to improve the consistency of its anti-Parkinsonian effect.

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Differential expression of FosB, c-Fos, and Zif268 in forebrain regions after acute or chronic l-DOPA treatment in a rat model of Parkinson's disease

Cited by 13 publications

References 26 publications

Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics

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