Category: Parkinson's Disease: Pathophysiology
Objective: To evaluate the changes in NCV and hyperpolarization latency of action potential of Sciatic nerve at the pre-motor phase in MPTP induced chronic PD rat in vivo model and the concomitant changes in striatal dopamine content, Sciatic nerve myelin diameter and Schwann cell number.
Background: In Parkinson’s disease, patients typically report to the clinic when symptoms of motor impairment start appearing. The most prescribed treatment for PD is Dopamine Replacement Therapy using pharmaceutical drugs that are known to have severe long-term side-effects. Pre-clinical studies increasingly show that recovery in this strategy works best if the cellular niche and cell repair is targeted during early onset of PD. The challenge therefore is to find an appropriate neurotool that can aid in diagnosis of PD at the early pre-motor phase through a simple quantitative measure.
Method: Using MPTP chronic PD model electrophysiology of Sciatic nerve was measured to detect NCV and compound action potential in reference to other pre-motor behaviour olfactory discrimination and motor behavioural studies motor coordination (rotarod) and locomotor (Actimeter) at different time points. Myelin diameter of Sciatic nerve (KPal staining), Schwann cell number and axonal dilation (H&E staining) was assessed through IHC. Corresponding striatal dopamine was measured using ELISA
Results: A distinct decrease in NCV was measured in the pre-motor phase i.e., during the initiation of olfactory discrimination stage without the onset of locomotor impairments. This was accompanied with a significant increase in absolute refractive period was observed from the 1st week post MPTP administration in the premotor stage wherein the motor co-ordination has not got affected. A corresponding significant thinning of myelin was observed in the KPal stained Sciatic nerve transverse sections from the pre-motor stage. The Schwann cell number as estimated from the longitudinal sections of the H&E-stained Sciatic nerve showed a decline from this pre-motor stage along with decrease in striatal dopamine levels.
Conclusion: This quantitative measure of NCV thus can serve as an appropriate neurotool to confirm the pre-motor stage in PD, indicating an eventual onset of locomotor and motor impairment stage.
To cite this abstract in AMA style:I. Datta, K. Mondal, A. Kaushal. Fundamental changes in Nerve Conduction Velocity and hyperpolarization latency of action potential of Sciatic nerve at the pre-motor phase in a chronic PD in vivo model: a neurotool for Parkinson’s disease diagnosis [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/fundamental-changes-in-nerve-conduction-velocity-and-hyperpolarization-latency-of-action-potential-of-sciatic-nerve-at-the-pre-motor-phase-in-a-chronic-pd-in-vivo-model-a-neurotool-for-parkinson/. Accessed September 22, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/fundamental-changes-in-nerve-conduction-velocity-and-hyperpolarization-latency-of-action-potential-of-sciatic-nerve-at-the-pre-motor-phase-in-a-chronic-pd-in-vivo-model-a-neurotool-for-parkinson/