Androgen Regulates Brain-Derived Neurotrophic Factor in Spinal Motoneurons and Their Target Musculature

Abstract

Trophic factors maintain motoneuron morphology and function in adulthood. Brain-derived neurotrophic factor (BDNF) interacts with testosterone to maintain dendritic morphology of spinal motoneurons. In addition, testosterone regulates BDNF's receptor (trkB) in motoneurons innervating the quadriceps muscles as well as in motoneurons of the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB). Given these interactive effects, we examined whether androgen might also regulate BDNF in quadriceps and SNB motoneurons and their corresponding target musculature. In both motoneuron populations, castration of males reduced BDNF immunolabeling, and this effect was prevented with testosterone replacement. ELISA for BDNF in the target musculature of quadriceps (vastus lateralis, VL) and SNB (bulbocavernosus, BC) motoneurons revealed that BDNF in the VL and BC muscles was also regulated by androgen. However, although castration significantly decreased BDNF concentration in the VL muscle, BDNF concentration in the BC muscle was significantly increased in castrates. Treatment of castrated males with testosterone maintained BDNF levels at those of intact males in both sets of muscles. Together, these results demonstrate that androgens regulate BDNF in both a sexually dimorphic, highly androgen-sensitive neuromuscular system as well as a more typical somatic neuromuscular system. Furthermore, in addition to the regulation of trkB, these studies provide another possible mechanism for the interactive effects of testosterone and BDNF on motoneuron morphology. More importantly, by examining both the motoneurons and the muscles they innervate, these results demonstrate that within a neural system, BDNF levels in different components are differentially affected by androgen manipulation.

Brain-derived neurotrophic factor plasma levels in patients with Turner syndrome

“…BDNF was positively and strongly linked to T serum concentrations, and this relation was of strong statistical significance (p50.0001). Link between T and BDNF is supported by recently published experimental data from animal studies by Bakos et al [29] and Verhovshek et al [30]. In former, plasma testosterone positively correlated with hippocampal BDNF in female but not male rats [29].…”

Parental brain‐derived neurotrophic factor genotype, child prosociality, and their interaction as predictors of parents’ warmth

“…Various studies in mice (Advani et al., 2009; Ren‐Patterson et al., 2006) and in humans (Shalev et al., 2009; Verhagen et al., 2010) have shown a sex difference in the effect of BDNF. This difference may be related to the interactions between BDNF and sex hormones such as estradiol (Begliuomini et al., 2007; Sohrabji et al., 1995) and testosterone (Hill et al., 2012; Verhovshek et al., 2010). Another explanation for the sex difference in the interaction effect might lie in the lower variability found for maternal warmth compared to paternal warmth.…”

“…In humans, the val66met polymorphism of the BDNF gene affects the onset of multiple sclerosis (MS) only in men and increases the risk of MS only in women (Mirowska‐Guzel, Mach, Gromadzka, Czlonkowski, & Czlonkowska, 2008). These differences may be explained by interactions between BDNF and sex hormones such as estradiol (Begliuomini et al., 2007; Sohrabji, Miranda, & Toran‐Allerand, 1995) and testosterone (Hill, Wu, Kwek, & van den Buuse, 2012; Verhovshek, Cai, Osborne, & Sengelaub, 2010). In rats, estrogen has been shown to regulate BDNF mRNA levels, possibly via an estrogen response element on the BDNF gene (Sohrabji et al., 1995).…”

“…In rats, estrogen has been shown to regulate BDNF mRNA levels, possibly via an estrogen response element on the BDNF gene (Sohrabji et al., 1995). Castration of male rats reduced BDNF protein levels in motoneurons, an effect that was prevented with testosterone administration (Verhovshek et al., 2010). In women, for example, BDNF plasma concentrations have been found to change according to hormonal status (menstrual cycle, amenorrhea, and menopause; Begliuomini et al., 2007).…”

Cellular and Molecular Mechanisms of the Effects of Sex Hormones on the Nervous System

“…Testosterone administration was shown to increase BDNF protein levels in motoneurons of spinal nucleus of the bulbocavernosus of castrated male rats [102]. Gonadectomy induces a significant decrease in the protein levels of BDNF and its downstream target post-synaptic density protein 95 (PSD-95) in the hippocampal CA1 area, which is reversed by testosterone replacement [78].…”