Testosterone manipulation protects motoneurons from dendritic atrophy after contralateral motoneuron depletion

Abstract

Dendritic morphology is reactive to many kinds of injuries, including axotomy and deafferentation. In this study, we examined the response of motoneurons in the spinal nucleus of the bulbocavernosus (SNB), an androgen-dependent population of motoneurons in the lumbar spinal cord of the rat, to partial motoneuron depletion. We depleted SNB motoneurons on one side only of the spinal cord by unilateral intramuscular injection of a retrogradely transported form of saporin, and examined the morphology of contralateral SNB motoneurons. Motoneuron morphology was assessed in normal control males, gonadally intact saporin-treated males, and saporin-treated males who had been castrated 6 weeks previously and given testosterone replacement beginning at the time of saporin injection. Untreated castrated males served as an additional control group. Four weeks after saporin treatment, SNB motoneurons contralateral to the saporin injection were retrogradely labeled with horseradish peroxidase conjugated to the cholera toxin B subunit and reconstructed in three dimensions. In gonadally intact males, unilateral motoneuron depletion caused regressive changes in contralateral SNB motoneurons: Soma size and dendritic length were both decreased. However, testosterone manipulation (i.e., castration followed by testosterone replacement) completely prevented the dendritic retraction. These data suggest a therapeutic role for testosterone in preventing, or accelerating recovery from, dendritic atrophy induced by motoneuron injury.

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

“…Previous studies have demonstrated that neither axonal transport of BHRP (Leslie et al, 1991) nor dendritic transport as demonstrated by the rostrocaudal or radial extent of dendritic labeling (Kurz et al, 1991;Goldstein and Sengelaub, 1994;Hebbeler et al, 2002;Fargo and Sengelaub, 2004b) are affected by hormone levels. Thus, in the present study, we believe that the differences we observed across hormone treatment groups reflect true dendritic atrophy in surviving motoneurons in untreated and estradiol-treated animals, which is attenuated by treatment with androgens.…”

“…Saporin is a type I ribosome inactivating protein; it kills cells by irreversibly inactivating ribosomes and thereby halting protein synthesis (Stirpe et al, 1983(Stirpe et al, , 1992. This form of saporin is retrogradely transported from the site of injection, and unilateral injection of saporin into the BC/LA muscle complex kills approximately 60% of ipsilateral SNB motoneurons within 3-6 days, while sparing the nearby contralateral SNB motoneurons (Fargo and Sengelaub, 2004b).…”

Androgen-sensitivity of somata and dendrites of spinal nucleus of the bulbocavernosus (SNB) motoneurons in male C57BL6J mice

“…There are several reasons why we do not think this is the case. In rats, androgens have been shown to affect overall dendritic length without affecting the radial extent of the SNB dendritic field or rostrocaudal extent (Kurz et al, 1991;Fargo and Sengelaub, 2004). In our analysis of dendritic length, we included a rough measure of radial extent in which the area occupied by SNB dendrites in each section was traced, and found no difference in the means (± SEM) between castrated (389340 ± 11711 μm²) and intact animals (406961 ± 15848 μm²).…”

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 .…”