Androgenic, but not estrogenic, protection of motoneurons from somal and dendritic atrophy induced by the death of neighboring motoneurons

Abstract

Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the bulbocavernosus (SNB). SNB motoneurons undergo marked dendritic and somal atrophy following the experimentally induced death of other nearby SNB motoneurons. However, treatment with testosterone at the time of lesioning attenuates this atrophy. Because testosterone can be metabolized into the estrogen estradiol (as well as other physiologically active steroid hormones), it was unknown whether the protective effect of testosterone was an androgen effect, an estrogen effect, or both. In the present experiment, we used a retrogradely transported neurotoxin to kill the majority of SNB motoneurons on one side of the spinal cord only in adult male rats. Some animals were also treated with either testosterone, the androgen dihydrotestosterone (which cannot be converted into estradiol), or the estrogen estradiol. As seen previously, partial motoneuron loss led to reductions in soma area and in dendritic length and extent in surviving motoneurons. Testosterone and dihydrotestosterone attenuated these reductions, but estradiol had no protective effect. These results indicate that the neuroprotective effect of testosterone on the morphology of SNB motoneurons following partial motoneuron depletion is an androgen effect rather than an estrogen effect.

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

“…Consistent with most other morphological effects in adult SNB motoneurons, the neuroprotective effects of steroid treatment appear to be strictly androgenic, as treatment with either T or DHT, but not EB, attenuates induced somal and dendritic atrophy following saporin injections (Fargo and Sengelaub, 2007). Thus, the SNB stands in contrast to some other areas in the nervous system, where estradiol has powerful neuroprotective effects (Henderson and Reynolds, 2002;Hoffman et al, 2006).…”

“…Local blockade of estrogen receptors at the BC muscle of gonadally intact males results in severely reduced dendritic lengths similar to those seen in castrates, whereas local administration of estradiol to the BC muscle of castrated males supports dendritic growth. This estrogenic influence is limited to the early postnatal period: the morphology of SNB motoneurons is insensitive to estrogens after 4 weeks of age (Goldstein and Sengelaub, 1994;Hebbeler et al, 2001;Warren and Sengelaub, 2002) or in adulthood (Forger et al, 1992;Fargo and Sengelaub, 2007). The transient influence of estrogens on SNB dendritic growth is coincident with a period in which high levels of NMDA receptors are expressed in the spinal cord, and locally in the SNB nucleus (Verhovshek et al, 2005).…”

Inhibition of Cytosolic Phospholipase A2Has Neuroprotective Effects on Motoneuron and Muscle Atrophy after Spinal Cord Injury

“…normal development 24,33,34 , after changes in dendritic interactions 33 and afferent input [35][36][37] , and after injury 6,[21][22][23]38 .…”

Molecular Changes at the Post-Synapse and Improved Motor Function Suggest Accelerated Recovery with SARM Treatment in an Androgen-Depleted Animal Model of Nerve Injury

“…Brown, et al has shown that agonists to the androgen receptor speed up the recovery time after sciatic nerve crush [14]. Furthermore, androgen treatment in the context of peripheral neurotoxicity (using saporin) was shown to be neuroprotective [15].…”