Brain-Derived Neurotrophic Factor and Androgen Interact in the Maintenance of Dendritic Morphology in a Sexually Dimorphic Rat Spinal Nucleus

Yang, Liang-Yo; Verhovshek, Tom; Sengelaub, Dale R.

doi:10.1210/en.2003-0853

Cited by 74 publications

(58 citation statements)

References 62 publications

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“…In B6D2F1 mice, the length of SNB dendrites did not appear to be dependent on adult levels of androgen. While there is no information to date on the mechanisms underlying the androgenic regulation of dendrites in mice, we can draw again from evidence obtained from rats which suggests that androgens in adulthood act directly on the BC/LA muscles to indirectly regulate the length of SNB dendrites (Rand & Breedlove, 1995) and this androgen action may be mediated via some muscle-derived factor such as brain derived neurotrophic factor (Yang et al, 2004). We report that BC/LA muscle mass in adult C57BL6J mice is highly androgen-dependent, as in rats (Venable, 1966).…”

Section: Discussionmentioning

confidence: 98%

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

Zuloaga

Morris

Monks

et al. 2007

Hormones and Behavior

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In rats, androgens in adulthood regulate the morphology of motoneurons in the spinal nucleus of the bulbocavernosus (SNB), including the size of their somata and the length of their dendrites. There are conflicting reports about whether androgens exert similar influences on SNB motoneurons in mice. We castrated or sham-operated C57BL6J mice at 90 days of age and, thirty days later, injected cholera toxin conjugated horseradish peroxidase into the bulbocavernosus muscle (to label SNB motoneurons) on one side, and into intrinsic foot muscles contralaterally (to label motoneurons of the retrodorsolateral nucleus (RDLN)). Castrated mice had significantly smaller SNB somas compared to sham operated mice while there were no differences in soma size of RDLN motoneurons. Dendritic length in C57BL6J mice, estimated in 3-dimensions, also decreased significantly after adult castration. In rats, androgens act directly through androgen receptors (AR) in SNB motoneurons to control soma size and nearly all their SNB motoneurons contain AR. Since SNB somata in C57BL6J mice shrank after adult castration, we used immunocytochemistry to characterize AR expression in SNB cells as well as motoneurons in the RDLN and dorsolateral nucleus (DLN). A pattern of labeling matched that seen previously in rats: the highest percentage of AR-immunoreactive motoneurons are in the SNB (98%), the lowest in the RDLN (25%), and an intermediate number in the DLN (78%). This pattern of AR labeling is consistent with the possibility that androgens also act directly on SNB motoneurons in mice to regulate soma size in mice.

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Section: Discussionmentioning

confidence: 98%

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

Zuloaga

Morris

Monks

et al. 2007

Hormones and Behavior

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“…The BC/LA muscles produce brain-derived neurotrophic factor (BDNF) (Yang and Arnold, 1999). By applying BDNF peripherally to cut BC/LA nerves, Yang et al (2004) showed that SNB dendritic morphology can be regulated by trophic substances from the neuromuscular periphery as long as testosterone is also present. The requirement for testosterone may be at least partially due to the fact that the expression of the BDNF receptor, trkB, in SNB motoneurons is regulated by T: motoneurons of castrated animals deprived of T show reduced expression of trkB receptors compared to motoneurons of intact animals or castrated animals given T replacement (Osborn et al, 2007;Ottem et al, 2007).…”

Section: Neurotherapeutic Effectsmentioning

confidence: 99%

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

Sengelaub

Forger

2008

Hormones and Behavior

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Cell number in the spinal nucleus of the bulbocavernosus (SNB) of rats was the first neural sex difference shown to differentiate under the control of androgens, acting via classical intracellular androgen receptors. SNB motoneurons reside in the lumbar spinal cord and innervate striated muscles involved in copulation, including the bulbocavernosus (BC) and levator ani (LA). SNB cells are much larger and more numerous in males than in females, and the BC/LA target muscles are reduced or absent in females. The relative simplicity of this neuromuscular system has allowed for considerable progress in pinpointing sites of hormone action, and identifying the cellular bases for androgenic effects. It is now clear that androgens act at virtually every level of the SNB system, in development and throughout adult life. In this review we focus on effects of androgens on developmental cell death of SNB motoneurons and BC/LA muscles; the establishment and maintenance of SNB motoneuron soma size and dendritic length; BC/LA muscle morphology and physiology; and behaviors controlled by the SNB system. We also describe new data on neurotherapeutic effects of androgens on SNB motoneurons after injury in adulthood.

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“…In animal studies, exercise increases production of local growth factors including brain-derived neuotropic factor (BDNF) that may affect brain function (10). Testosterone and BDNF interact to maintain dendritic morphology in the rat spinal nucleus (11). Therefore, it is conceivable that the addition of an exercise program to testosterone administration may have additive effects on mental function and quality of life in elderly men as well.…”

Section: Introductionmentioning

confidence: 99%

Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men

Katznelson

Robinson²,

Coyle³

et al. 2006

eur j endocrinol

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Objective: One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging. In this study, we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency. Design: Double-blind, placebo-controlled randomized study (testosterone), and additional randomization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency. Methods: Seventy sedentary, community dwelling men were randomized to a 5 mg testoderm transdermal system applied daily vs placebo system, and additionally randomized to a home-based resistance exercise program. Subjects were randomized to Group 1 (testosterone plus exercise), Group 2 (testosterone plus no exercise), Group 3 (placebo plus exercise), and Group 4 (placebo plus no exercise). Endpoints included quality of life (assessed by the short form-36 questionnaire) and body composition (measured by dual x-ray absorptiometry scan). Results: Serum testosterone increased by a mean of 10.0G1.9, 6.6G1.6, 0.52G0.6, and 0.5G 0.6 nmol/l in Groups 1, 2, 3, and 4 respectively. There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning (PZ0.03), role physical (PZ0.01), general health (PZ0.049), and social functioning (PZ0.04). There were no effects of testosterone or exercise on quality of life alone, nor in body composition parameters. Conclusions: Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program. The combination of testosterone and exercise may be an important strategy in the elderly, though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well.European Journal of Endocrinology 155 867-875

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Brain-Derived Neurotrophic Factor and Androgen Interact in the Maintenance of Dendritic Morphology in a Sexually Dimorphic Rat Spinal Nucleus

Cited by 74 publications

References 62 publications

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

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

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

Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men

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