Neuroprotective effect of testosterone treatment on motoneuron recruitment following the death of nearby motoneurons.
Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have previously shown that motoneuron death induces marked dendritic atrophy in surviving nearby motoneurons. Additionally, in quadriceps motoneurons, this atrophy is accompanied by decreases in motor nerve activity. However, treatment with testosterone partially attenuates changes in both the morphology and activation of quadriceps motoneurons. Testosterone has an even larger neuroprotective effect on the morphology of motoneurons of the spinal nucleus of the bulbocavernosus (SNB), in which testosterone treatment can completely prevent dendritic atrophy. The present experiment was performed to determine whether the greater neuroprotective effect of testosterone on SNB motoneuron morphology was accompanied by a greater neuroprotective effect on motor activation. Right side SNB motoneurons were killed by intramuscular injection of cholera toxin-conjugated saporin in adult male Sprague-Dawley rats. Animals were either given Silastic testosterone implants or left untreated. Four weeks later, left side SNB motor activation was assessed with peripheral nerve recording. The death of right side SNB motoneurons resulted in several changes in the electrophysiological response properties of surviving left side SNB motoneurons, including decreased background activity, increased response latency, increased activity duration, and decreased motoneuron recruitment. Treatment with exogenous testosterone attenuated the increase in activity duration and completely prevented the decrease in motoneuron recruitment. These data provide a functional correlate to the known protective effects of testosterone treatment on the morphology of these motoneurons, and further support a role for testosterone as a therapeutic agent in the injured nervous system.
Fargo
Keith N
KN
Research and Development Service, Edward Hines, Jr. VA Hospital, Hines, Illinois 60141, USA. keith.fargo@va.gov
Foster
Allison M
AM
Sengelaub
Dale R
DR
D000818:Animals; D001284:Atrophy; D016923:Cell Death; D004558:Electric Stimulation; D004594:Electrophysiology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011999:Recruitment, Neurophysiological / Q000187:drug effects* / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D013739:Testosterone / Q000494:pharmacology*
D013739:Testosterone