Abnormal bidirectional plasticity-like effects in Parkinson's disease

Huang, Yufei; Rothwell, John C.; Lu, Chin‐Song; Chuang, Wen-Li; Chen, Rou‐Shayn

doi:10.1093/brain/awr158

Cited by 111 publications

(115 citation statements)

References 45 publications

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“…With regard to LID, the enlargement of dendritic spines (Fig. 5A and 5C) would account for the lack of depotentiation-like cortical plasticity in patients with LID (Huang et al, 2012). In fact, using patch-clump recording the supersensitivity of IT-type neurons was confirmed in the LID model ( Fig.…”

Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 87%

“…Conversely, the induction of LTD causes spine shrinkage (Zhou et al, 2004). The abnormal preservation of LTP-like plasticity in the motor cortex in patients with dyskinesia (Huang et al, 2012) represents supersensitivity of the motor cortex. With regard to LID, the enlargement of dendritic spines (Fig.…”

Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 99%

“…6A and 6C). Accordingly, the enlargement of spines could be a cellular mechanism that explains the abnormal plasticity in the motor cortex in PD patients with dyskinesia (Huang et al, 2012). …”

Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 99%

“…Using this approach, PD patients with LID exhibit a lack of depotentiation-like cortical plasticity (Huang et al, 2012). Levodopa fails to effectively normalize the excitability of inhibitory systems and does not restore motor cortical plasticity in PD patients with dyskinesia, in contrast to its effects in PD patients without dyskinesia (Morgante et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The morphological properties of dendritic spines are intimately linked with synaptic functions; i.e., changes in synaptic plasticity are often accompanied by changes in spine size (Kasai et al, 2010a(Kasai et al, , 2010b. Accordingly, morphological examinations of dendritic spines in pyramidal neurons of the motor cortex in animal models should shed light on the mechanisms underlying the cortical synaptic abnormalities observed in PD patients with LID (Morgante et al, 2006;Suppa et al, 2011;Huang et al, 2012;Kishore et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia

Ueno

Yamada

Nishijima

et al. 2014

Neurobiology of Disease

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Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats  Spine enlargement and hyperexcitability in intratelencephalic-type corticostriatal neurons in M1 may be linked to development of dyskinesia.

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Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 87%

Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 99%

Section: Morphological Changes In Dendritic Spines Of It-type Neuronsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia

Ueno

Yamada

Nishijima

et al. 2014

Neurobiology of Disease

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Levodopa‐induced dyskinesia in Parkinson disease: Sleep matters

Amato¹,

Manconi²,

Sarasso

et al. 2018

Annals of Neurology

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Objective: The spectrum of clinical symptom changes during the course of Parkinson disease (PD). Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal involuntary movements as the disease progresses. This levodopa-induced dyskinesia (LID) has been associated with abnormal cortical plasticity. Because slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LID. Methods: Thirty-six patients at different stages of PD underwent whole-night video polysomnography-high-density electroencephalography (vPSG-hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into 3 groups by disease stage-(1) de novo (n = 9), (2) advanced (n = 13), and (3) dyskinetic (DYS; n = 14)-were compared to an age-matched control group (n = 12). The SWA-NREM content of the vPSG-hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2-T3-T4 were considered early sleep and were compared to T7-T8-T9, representing late sleep. Results: We found that all groups, except the DYS group, manifested a clear-cut SWA decrease between early and late sleep. Interpretation: Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID.

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Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

Espay

Morgante

Merola

et al. 2018

Annals of Neurology

247

204

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Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. ANN NEUROL 2018;84:797-811 D yskinesia, often referred to as L-dopa-induced dyskinesia (LID) to recognize L-dopa as the major contributor, is a motor complication arising in patients with Parkinson disease (PD) on chronic L-dopa treatment, largely in a dose-dependent fashion-except when given as an infusion, such as in L-dopa/carbidopa intestinal gel. 1 LID is phenomenologically recognized as chorea/choreoathetoid movements appearing initially on the more affected body side. LID occurs in 40% of patients after 4 years on L-dopa treatment, with risk especially high in younger patients treated with higher doses of L-dopa. 2 This review focuses on aspects of phenomenology, pathophysiology, and therapeutics that have undergone revisions or updates in recent years, emphasizing those of most relevance for modern clinical care and future research. We highlight the under-recognized diphasic dyskinesia, which is often mischaracterized as a peak-dose phenomenon and therefore mismanaged. We review evidence that corrects the misinterpretation of prior clinical trial data surmising LID as a function of duration of Ldopa exposure rather than duration of disease, justifying the inappropriate but still lingering recommendation to postpone L-dopa treatment as long as possible to "delay" the appearance of LID. 3 We also review the latest pathophysiologic concepts at the molecular, synaptic, and network levels, to provide the rationale for currently available as well as emerging treatments. Peak-Dose versus Diphasic DyskinesiaPeak-Dose Dyskinesia. Chorea that may be generalized or affect the more affected side or upper body often occurs during the therapeutic window of a L-dopa dose cycle View this article online at wileyonlinelibrary.com.

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Abnormal bidirectional plasticity-like effects in Parkinson's disease

Cited by 111 publications

References 45 publications

Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia

Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia

Levodopa‐induced dyskinesia in Parkinson disease: Sleep matters

Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

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