Androgenic regulation of the central glia response following nerve damage

Abstract

Current research on the effects of gonadal steroids on the brain and spinal cord indicates that these agents have profound trophic effects on many aspects of neuronal functioning, including cell survival, growth and metabolism, elaboration of processes, synaptogenesis, and neurotransmission (Jones et al., 1985; Luine, 1985; Nordeen et al., 1985; Matsumoto et al., 1988a,b; Gould et al., 1990). Since many of the aspects of normal neuronal functioning altered by gonadal steroids are affected by injury to the nervous system, we initiated a series of experiments designed to exploit the trophic capabilities of steroids as therapeutic agents in neuronal injury and repair (Kujawa et al., 1989, 1991; Kujawa and Jones, 1990). Three steroid‐sensitive model systems were used for these studies: the hamster facial motoneuron, the rat sciatic motoneuron, and the hamster rubrospinal motoneuron. The results of our initial series of experiments suggest that androgens, and possibly estrogens, act either directly or indirectly on the injured motoneuron and enhance elements of the neuronal reparative response that are critical to successful recovery of function. Recently, we discovered that gonadal steroids may also modulate the central glia response to nerve damage. In this review, a summary of our data identifying a therapeutic role for androgens in enhancing the reparative response of motoneurons to injury is presented. This is followed by a discussion of the effects of androgens on the glial response to injury. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 560–573, 1999

CD4-Positive T Cell-Mediated Neuroprotection Requires Dual Compartment Antigen Presentation

“…Motoneuron cell death after injury or resulting from degenerative diseases such as amyotrophic lateral sclerosis (ALS) is a perplexing phenomenon for which investigators have highlighted many complex mechanisms required for motoneuron survival after nerve injury or during degenerative diseases (Sendtner et al, 1996;Jones et al, 1999;Wong et al, 2002). Although the CNS has historically been considered an immune-privileged site, insults to the nervous system elicit a range of immune-mediated responses that convey both deleterious and beneficial effects on the nervous system (Troost et al, 1989;Fu and Gordon, 1997;Serpe et al, 1999Serpe et al, , 2000Serpe et al, , 2003Jones et al, 2002).…”

Androgen regulation of axon growth and neurite extension in motoneurons

“…This is accompanied by an upregulation in the facial motor nucleus of the glial marker GFAP at both the mRNA (Jones et al, 1997c) and protein (Coers et al, 2002) levels. However, androgen treatment attenuates the process of synaptic stripping, preserving central input to the motoneurons (Jones et al, 1997b), as well as attenuating the axotomy-induced upregulation of GFAP (Coers et al, 2002;Jones et al, 1997c; for a more in-depth review of glial mediation of androgen effects in nerve regeneration, see Jones et al, 1999a). Similar effects have also been observed in the rat (see Moran and Graeber, 2004, for a review).…”

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

“…Various AR coregulators can further modulate the transcriptional regulation of target genes [11]. AR receptors are expressed in neurons and glial cells and their expression can be regulated by injury and by circulating testosterone concentration [12][13][14]. AR mRNA is downregulated post-orchidectomy and after axotomy [12].…”