Antagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia

Schuster, Stefan; Doudnikoff, Évelyne; Rylander, Daniella; Berthet, Amandine; Aubert, Incarnation; Ittrich, Carina; Bloch, Bertrand; Cenci, M. Angela; Surmeier, D. James; Hengerer, Bastian; Bézard, Erwan

doi:10.1016/j.biopsych.2008.09.008

Cited by 82 publications

(75 citation statements)

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“…In such conditions, L-DOPA induces a gradual development of dyskinetic-like AIMs. On day 29, 21 rats were scored as nondyskinetic (score ϭ 0.71), and 44 rats were scored as dyskinetic (score ϭ 8.3) after observation by a trained investigator as described previously (Meissner et al, 2006;Schuster et al, 2008Schuster et al, , 2009) using a validated rating scale (Cenci et al, 1998;Lundblad et al, 2002 (Mach et al, 2004) together with L-DOPA. Doses were chosen for their respective ability to induce D 1 R internalization (Dumartin et al, 1998) and to reduce dyskinesia severity (Bézard et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

Berthet¹,

Porras²,

Doudnikoff³

et al. 2009

J. Neurosci.

128

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Section: Methodsmentioning

confidence: 99%

Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

Berthet¹,

Porras²,

Doudnikoff³

et al. 2009

J. Neurosci.

128

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“…Peptide experiments were conducted on 11 dyskinetic rats. The 4 AIM categories (limb, axial, orolingual, and locomotive) were scored using a validated rating scale (33, 34) for 1 minute every 20 minutes for 2 hours (total 6 observations; maximal score for each observation, 16; maximal total score per session, 96) by a trained investigator as described previously (41,80). Figures display the sum of the axial, limb, and orolingual AIMs.…”

Section: Rat Experimentsmentioning

confidence: 99%

PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking

Porras¹,

Berthet²,

Dehay³

et al. 2012

J. Clin. Invest.

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115

132

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l-DOPA-induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson's disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson's patients. IntroductionIn the striatum, dopamine (DA) terminals from the substantia nigra pars compacta (SNc) converge with glutamatergic signals from the cortex on dendritic spines of striatal medium spiny projecting GABAergic neurons (1, 2). The degeneration of the nigrostriatal pathway in Parkinson's disease (PD) induces complex modifications in both DA and glutamate signaling, leading to significant morphological and functional modifications in the striatal neuronal circuitry (3-5). Chronic DA replacement therapy with l-3,4-dihydroxyphenylalanine (l-DOPA) superimposes upon these DA depletion-induced changes, resulting in debilitating motor complications known as l-DOPAinduced dyskinesia (LID) (6-8). At the molecular level, the subcellular organization of and functional interactions between glutamate and DA receptors within the striatum are crucial both in the pathogenesis of PD (9) and in the development of LID (10, 11). LID has indeed been associated with plastic changes in postsynaptic neuronal targets in the striatum, including elevated extracellular levels of glutamate (12) and DA (13) and abnormal trafficking of DA D1 receptor (D1R) (14, 15) and of NMDA and AMPA glutamate receptor subunits (5,10,16,17). Such exaggerated DA and glutamate receptor expression at the plasma membrane results in abnormal activation of key signaling kinases (18)(19)(20)(21)(22). All these changes point to dysfunctional interactions between DA and glutamate neurotransmission in LID (5,23,24), although the molecular mechanisms remain elusive, despite recent progress (14, 25).The membrane-associated guanylate kinase (MAGUK) proteins, such as postsynaptic density 95 (PSD-95), organize ionotropic glutamate receptors and their associated signaling proteins, regulating the strength of synaptic activity. Interestingly, PSD-95 might also interact with DA D1R (26), thereby potentially regulating DA

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“…It has previously been reported that isradipine has a neuroprotective effect on Parkinson's disease in mice [6]. Furthermore, it has been shown that isradipine decreased involuntary movements in the Parkinson's rat model in a dose dependent manner [11,15]. Epidemiological studies suggest that calcium channel blockers prevent or slow the progression of AD.…”

Section: Discussionmentioning

confidence: 99%

Effects of Isradipine on Induced-Parkinson’s Disease in Rats

Komeili

Farajian-Mashhadi

2016

Zahedan J Res Med Sci

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Background: Parkinson's disease is the second most common neurodegenerative disease in developed countries. Recent studies have showed that there is a relation between neuron loss in Parkinson's disease and L-type calcium channel activity in pars compacta of substantia nigra. Therefore, it seems that calcium channel blockers can effect on this disease. Objectives: In this study, we evaluate the protective and therapeutic effects of isradipine on experimental Parkinson's model in rats. Materials and Methods: In this experimental study, 63 rats were allocated randomly in seven group including: intact, control, sham operated, lesion and lesion treated by 0.1, 0.2 or 0.4 mg/kg dosage of isradipine. L-type calcium channel blocker, isradipine was subcutaneously injected to treated rats in the doses of 0.1, 0.2 and 0.4 mg/kg/day, for four weeks, starting the day after a unilateral nigrostriatal 6-hydroxy dopamine (6-OHDA) lesion. Rotational tests with apomorphine and rigidity tests were conducted on all animal groups one week before the lesion experiments and four weeks after. Results: Administration of isradipine (0.1, 0.2 and 0.4 mg/kg/day for 4 weeks) decreased mean of rotation number and muscular rigidity score significantly compared with control group (P < 0.05). Conclusions: This study showed that isradipine has a therapeutic effect in a dose dependent manner on Parkinson's disease in rats.

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Antagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia

Cited by 82 publications

References 33 publications

Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking

Effects of Isradipine on Induced-Parkinson’s Disease in Rats

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Antagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia

Cited by 82 publications

References 33 publications

Pharmacological Analysis Demonstrates Dramatic Alteration of D1Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

Pharmacological Analysis Demonstrates Dramatic Alteration of D1Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking

Effects of Isradipine on Induced-Parkinson’s Disease in Rats

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Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia

Pharmacological Analysis Demonstrates Dramatic Alteration of D₁Dopamine Receptor Neuronal Distribution in the Rat Analog of l-DOPA-Induced Dyskinesia