Additive Effects of Ciliary Neurotrophic Factor and Testosterone on Motoneuron Survival; Differential Effects on Motoneuron Size and Muscle Morphology

Varela, Carly R.; Bengston, Lynn; Xu, Jun; MacLennan, A. John; Forger, Nancy G.

doi:10.1006/exnr.2000.7475

Cited by 15 publications

(10 citation statements)

References 43 publications

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“…Also, the intracellular dynamics of steroid hormone receptors should be considered [65, 66]. Neuromuscular junctions are formed in E15 rats [67]and the presence of AR is crucial for the motor unit development [23]. Thus, the presence of AR in E14–E15 MN is not surprising.…”

Section: Discussionmentioning

confidence: 99%

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Receptors to Steroid Hormones and Aromatase Are Expressed by Cultured Motoneurons but Not by Glial Cells Derived from Rat Embryo Spinal Cord

et al. 2004

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The aim of this study was to examine the expression of aromatase and receptors to steroid hormones in cultured motoneurons (MNs). We first developed an original method for obtaining rat MN cultures. Dissociated E15 rat spinal cords were purified using metrizamide and bovine serum albumin density gradients, and cells were then seeded on the culture substratum. We optimized the culture parameters and found that simple addition of rat muscle extract (ME) and conditioned culture medium (CM) from glial cell lines (GCL) derived from spinal cord were sufficient to obtain almost pure MN cultures. MNs were characterized by the presence of specific MN markers and electrophysiology. MNs could be kept alive for 2 weeks. We demonstrate that ME and CM are essential for MN development and survival respectively. Immunocytochemistry and aromatase activity assay indicated the presence of androgen and estrogen receptors as well as aromatase in MNs but not in GCL. This is the first report demonstrating the presence of both female and male sex hormone receptors and a key enzyme in steroid hormone metabolism in MNs and its absence in GCL, at least in our culture conditions. This in vitro model appears to be valuable for elucidating the impact of the sex hormone circuit in neuronal maturation. The relevance of this model for the comprehension of neurodegenerative diseases is discussed.

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Section: Discussionmentioning

confidence: 99%

“…In addition, the presence of ARs in MNs and in sensory neurons, the upregulation of AR expression by testosterone, and the impact of testosterone on MN morphology, maturation, survival and in target muscle size are well-documented [19, 20, 21, 22, 23]. The expression of estrogen receptors (ERs) prevails in sensory neurons [24].…”

Section: Introductionmentioning

confidence: 99%

Receptors to Steroid Hormones and Aromatase Are Expressed by Cultured Motoneurons but Not by Glial Cells Derived from Rat Embryo Spinal Cord

et al. 2004

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“…Androgen treatment administered either prenatally or in the early postnatal period masculinizes the perineal musculature of female rats and mice through the early postnatal period (C ihá k et al, 1970;Park et al, 1999;Varela et al, 2000) and into adulthood (Breedlove and Arnold, 1983b;Sachs and Thomas, 1985;Wagner and Clemens, 1989b;Tobin and Joubert, 1991). Treatment of female rats with T prenatally or within a week of birth causes an increase in both the volume of the perineal muscles and the number and size of fibers in the LA (Breedlove and Arnold, 1983b;Tobin and Joubert, 1991;Varela et al, 2000). Postnatal treatment administered more than a week after birth causes a lesser increase in adult BC-LA muscle mass (Breedlove and Arnold, 1983b).…”

Section: Androgen Treatment Of Femalesmentioning

confidence: 99%

Normal ontogeny of perineal muscles and testosterone levels in Mongolian gerbils; Response to testosterone in developing females

Siegford¹,

Mansouri²,

Ulibarri³

2003

Anat. Rec.

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The spinal nucleus of the bulbocavernosus (SNB) of Mongolian gerbils (Meriones unguiculatus) becomes sexually dimorphic during postnatal life, rather than prenatally as in rats. We therefore examined the early postnatal ontogeny of Mongolian gerbils, focusing on growth, serum testosterone (T) levels, and the sexually dimorphic perineal musculature innervated by the SNB. Serum T levels were higher in males than in females from birth through adulthood, with several early postnatal peaks and a large increase in T occurring during puberty in males. The SNB target muscles-the bulbocavernosus (BC) and levator ani (LA)-were present in both sexes on postnatal day 1 (PND1). Cross-sectional areas of BC fibers in males increased with age, and concurrently the myofibers of the BC became more fully developed and organized. In PND10 female pups, the BC muscle was virtually absent, while the LA muscle remained (although it was reduced in size). Postnatal treatment of female gerbils with androgen caused the BC muscle to remain and the LA muscle to become larger by PND10. Sexual dimorphism of the SNB develops differently in gerbils compared to other species, although its target muscles appear to respond to androgen in a manner similar to that in rats. Anat Rec Part A 275A: 997-1008, 2003.

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“…Postnatal androgen treatment of female gerbils on the day of birth results in three times as many SNB motoneurons compared with the number found in vehicle-treated females in adulthood, whereas neonatally castrated male gerbils have fewer SNB motoneurons adults compared with those of intact males (Decker et al, 1991;Siegford and Ulibarri, submitted). More SNB motoneurons are also seen in female rats and mice treated perinatally with TP (Breedlove and Arnold 1983b;Sachs and Thomas, 1985;Park et al, 1999;Varela et al, 2000). However, fewer, rather than more, SNB motoneurons are seen in adulthood when male rats are treated with TP neonatally or during midgestation, compared with control males (Sachs and Thomas, 1985).…”

Section: Discussionmentioning

confidence: 81%

Increase in motoneurons in the spinal nucleus of the bulbocavernosus of prepubertally castrated male Mongolian gerbils following delayed treatment with testosterone

Siegford

Ulibarri

2004

J of Comparative Neurology

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Sexual dimorphism in the spinal nucleus of the bulbocavernosus (SNB) of the Mongolian gerbil is achieved by two periods of postnatal increase, one in the first month after birth and one at puberty. The pubertal increase in motoneuron number is of particular interest because it occurs in a nearly adult animal. The purpose of this research was threefold. The first was to determine the response of the SNB in prepubertally castrated male gerbils receiving delayed hormone replacement as adults. Testosterone propionate (TP) treatment resulted in numbers of SNB motoneurons comparable to those seen in intact males, whereas androgen metabolites were less effective. The second purpose was to determine the latency of motoneurons to appear in response to TP. New SNB motoneurons appeared within 2 days of delayed TP replacement in prepubertally castrated males, and 16 days of treatment did not further increase SNB motoneuron numbers. The response of the motoneurons to TP appeared more rapid than the response of the bulbocavernosus (BC) muscle, scent gland, and seminal vesicles. The third purpose was to determine whether the new cells were connected to a target muscle. After 16 days of TP treatment, more motoneurons were labeled in the SNB following injection of a retrograde tract tracer into the BC muscle compared with the number seen in control animals. Thus, new motoneurons appeared in the SNB of prepubertally castrated male Mongolian gerbils within 2 days of the start of delayed TP treatment and were connected to a target within 16 days of TP treatment.

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Additive Effects of Ciliary Neurotrophic Factor and Testosterone on Motoneuron Survival; Differential Effects on Motoneuron Size and Muscle Morphology

Cited by 15 publications

References 43 publications

Receptors to Steroid Hormones and Aromatase Are Expressed by Cultured Motoneurons but Not by Glial Cells Derived from Rat Embryo Spinal Cord

Receptors to Steroid Hormones and Aromatase Are Expressed by Cultured Motoneurons but Not by Glial Cells Derived from Rat Embryo Spinal Cord

Normal ontogeny of perineal muscles and testosterone levels in Mongolian gerbils; Response to testosterone in developing females

Increase in motoneurons in the spinal nucleus of the bulbocavernosus of prepubertally castrated male Mongolian gerbils following delayed treatment with testosterone

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