Abstract
ABSTRACTParkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate‐putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia‐like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa‐induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa‐induced complications such as levodopa‐induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N‐methyl‐D‐aspartate receptor antagonists, alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa‐induced complications in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Highlights
Isoxazolepropanoic acid receptors into the postsynaptic membrane
The timing and duration of dopamine signals are important in controlling synaptic plasticity,[24] and they are dramatically distorted with levodopa treatment in Parkinson’s disease (PD) patients.[24]
The results demonstrated that the dendritic spine density of iSPNs was reduced by dopaminergic denervation and restored by high-dose levodopa treatment with the development of LID
Summary
Haruo Nishijima, MD, PhD ,1,2* Tatsuya Ueno, MD, PhD,[1,2] Yukihisa Funamizu, MD,[1] Shinya Ueno, MD, PhD,[2] and Masahiko Tomiyama, MD, PhD1,2. Isoxazolepropanoic acid receptors into the postsynaptic membrane Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa-induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. NISHIJIMA ET AL plasticity at axospinous synapses in the striatum and cortex.[21,22,23,24,25] A recent study demonstrated that dopamine promotes spine enlargement only during a narrow time window after the glutamatergic inputs at the level of single dendritic spines.[26] The timing and duration of dopamine signals are important in controlling synaptic plasticity,[24] and they are dramatically distorted with levodopa treatment in PD patients.[24] This distortion is likely to underlie LID. This leads to synaptic plasticity and spine pathological changes, resulting from dopaminergic denervation and further levodopa treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
