EMG Testing throughout behavioral recovery after rat sciatic nerve crush injury results in exuberant motoneuron dendritic hypertrophy

Article type: Research Article

Authors: Meadows, Rena M.^a | Richards, Sarah M. E.V.^b | Kitsis, Michelle R.^b | Brown, Todd J.^a | Jones, Kathy J.^a | Sengelaub, Dale R.^{b; *}

Affiliations: [a] Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, Indiana | [b] Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana

Correspondence: [*] Corresponding author: Dale R. Sengelaub, Psychology Building, Indiana University, 1101 East 10th Street, Bloomington, Indiana 47405. Tel.: (812) 855 9149; Fax: (812) 855 4691; E-mail: sengelau@indiana.edu.

Abstract: Background: Peripheral nerve injury (PNI) is the most common type of nerve trauma yet, while injured motoneurons exhibit a robust capacity for regeneration, behavioral recovery is protracted and typically poor. Neurotherapeutic approaches to PNI and repair have primarily focused on the enhancement of axonal regeneration, in terms of rate, axonal sprouting, and reconnection connectivity. Both electrical stimulation (ES) and treatment with androgens [e.g., testosterone propionate (TP)] have been demonstrated to enhance axonal sprouting, regeneration rate and functional recovery following PNI. To date, very little work has been done to examine the effects of ES and/or TP on dendritic morphology and organization within the spinal cord after PNI. Objective: The objective of the current study was to examine the impact of treatment with TP and ES, alone or in combination, on the dendritic arbor of spinal motoneurons after target disconnection via sciatic nerve crush injury in the rat. Methods: Rats received a crush injury to the sciatic nerve. Following injury, some animals received either (1) no further treatment beyond implantation with empty Silastic capsules, (2) electrical nerve stimulation immediately after injury, (3) implantation with Silastic capsules filled with TP, or (4) electrical nerve stimulation immediately after injury as well as implantation with TP. All of these groups of axotomized animals also received bi-weekly electromyography (EMG) testing. Additional groups of intact untreated animals as well as a group of injured animals who received no further treatment or EMG testing were also included. Eight weeks after injury, motoneurons innervating the anterior tibialis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Results: After nerve crush and ES and/or TP treatment, motoneurons innervating the anterior tibialis underwent marked dendritic hypertrophy. Surprisingly, this dendritic hypertrophy occurred in all animals receiving repeated bi-weekly EMG testing, regardless of treatment. When the EMG testing was eliminated, the dendritic arbor extent and distribution after nerve crush in the treated groups did not significantly differ from intact untreated animals. Conclusions:The ability of repeated EMG testing to so dramatically affect central plasticity following a peripheral nerve injury was unexpected. It was also unexpected that gonadal steroid hormones and/or ES, two neurotherapeutic approaches with demonstrated molecular/behavioral changes consistent with peripheral improvements in axonal repair and target reconnection, do not appear to impact central plasticity in a similar manner. The significance of peripheral EMG testing and resulting central plasticity reorganization remains to be determined.

Keywords: Axotomy, electrical stimulation, steroids, neuroprotection, morphology, dendrites

DOI: 10.3233/RNN-231379

Journal: Restorative Neurology and Neuroscience, vol. 41, no. 5-6, pp. 241-256, 2023