Is there hope that transpinal direct current stimulation corrects motoneuron excitability and provides neuroprotection in amyotrophic lateral sclerosis?

Marcin Bączyk,Daniel Zytnicki,Piotr Krutki

doi:10.14814/phy2.14706

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of largely unknown pathophysiology, characterized by the progressive loss of motoneurons (MNs). We review data showing that in presymptomatic ALS mice, MNs display reduced intrinsic excitability and impaired level of excitatory inputs. The loss of repetitive firing specifically affects the large MNs innervating fast contracting muscle fibers, which are the most vulnerable MNs in ALS. Interventions that aimed at restoring either the intrinsic excitability or the synaptic excitation result in a decrease of disease markers in MNs and delayed neuromuscular junction denervation. We then focus on trans‐spinal direct current stimulation (tsDCS), a noninvasive tool, since it modulates the activity of spinal neurons and networks. Effects of tsDCS depend on the polarity of applied current. Recent work shows that anodal tsDCS induces long‐lasting enhancement of MN excitability and synaptic excitation of spinal MNs. Moreover, we show preliminary results indicating that anodal tsDCS enhances the excitatory synaptic inputs to MNs in ALS mice. In conclusion, we suggest that chronic application of anodal tsDCS might be useful as a complementary method in the management of ALS patients.

Highlights

Recent data demonstrate that the excitability changes of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS, a prominent neurodegenerative disease of MNs) depend on the physiological type of motor unit and evolve with disease progression
We review recent work suggesting that trans-spinal direct current stimulation (tsDCS) could be used to compensate for the changes in intrinsic excitability of MNs, or synaptic excitation, and hopefully to deliver some neuroprotection in Amyotrophic lateral sclerosis (ALS)
Recent experiments suggest that vulnerable MNs become intrinsically hypoexcitable and that their excitatory synapses are impaired in the SOD1G93A mice

Summary

Introduction

Recent data demonstrate that the excitability changes of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS, a prominent neurodegenerative disease of MNs) depend on the physiological type of motor unit and evolve with disease progression. We review recent work suggesting that tsDCS could be used to compensate for the changes in intrinsic excitability of MNs, or synaptic excitation, and hopefully to deliver some neuroprotection in ALS. In ALS mouse models, time-dependent alterations of intrinsic MN excitability that start long before degeneration onset have been shown in both vulnerable and resistant MNs. In these studies it was found that MNs are hyperexcitable at embryonic stages in the SOD1 G93Amice (input resistance is increased, rheobase is decreased and slope of the frequency–current relationship is increased; Martin et al, 2013; Pieri et al, 2003).

Results

Conclusion