Androgen regulation of axon growth and neurite extension in motoneurons

Fargo, Keith N.; Galbiati, M.; Foecking, Eileen M.; Poletti, Angelo; Jones, Kathryn J.

doi:10.1016/j.yhbeh.2008.01.014

Cited by 51 publications

(42 citation statements)

References 119 publications

(168 reference statements)

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“…To affect axonal calibre, it would be necessary for testosterone to influence the number and/or properties of microtubules and/or neurofilaments [Hoffman et al, 1987;Marszalek et al, 1996]. This hypothesis is consistent, for example, with experimental findings of testosterone-induced upregulation of b-tubulin expression [Butler et al, 2001;Matsumoto et al, 1994], or androgen regulation of axonal growth in motoneurons [for a review, see Fargo et al, 2008]. Since the effect of testosterone during adolescence would obviously relate to the late maturation of axon calibre, this phenomenon would likely affect the whole fibre spectrum of the pCST, small or large, causing the decrease in aGMd.…”

Section: Hypothesis 2: Age and Sexmentioning

confidence: 55%

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain

Hervé¹,

Leonard²,

Perron³

et al. 2009

Human Brain Mapping

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With anatomical magnetic resonance imaging, the signal intensity of the corticospinal tract (CST) at the level of the internal capsule is often paradoxically similar to that of grey matter. As shown previously in histological studies, this is likely due to the presence of very large axons. We measured the apparent grey-matter density (aGMd) of the putative CST (pCST) in a large cohort of adolescents (n = 409, aged 12-18 years). We tested the following hypotheses: (1) The aGMd in the pCST shows a hemispheric asymmetry that is, in turn, related to hand preference; (2) the maturation of the CST during adolescence differs between both sexes, due to the influence of testosterone; (3) variations in aGMd in the pCST reflect inter-individual differences in manual skills. We confirmed the first two predictions. Thus, we found a strong left> right hemispheric asymmetry in aGMd that was, on average, less marked in the 40 left-handed subjects. Apparent GMd in the pCST increased with age in adolescent males but not females, and this was particularly related to rising plasma levels of testosterone in male adolescents. This finding is compatible with the idea that testosterone influences axonal calibre rather than myelination. The third prediction, namely that of a relationship between age-related changes in manual skills and maturation of the pCST, was not confirmed. We conclude that the leftward asymmetry of the pCST may reflect an early established asymmetry in the number of large corticomotoneuronal fibres in the pCST.

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Section: Hypothesis 2: Age and Sexmentioning

confidence: 55%

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain

Hervé¹,

Leonard²,

Perron³

et al. 2009

Human Brain Mapping

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“…The next two papers tackle the role of androgens in neuromuscular function and disease (Fargo et al, 2008;Monks et al, 2008). It is clear from these two papers that androgens can either promote or interfere with neuromuscular function, depending on other factors.…”

Section: Role Of Ars In Neurodegeneration and Recovery Of Functionmentioning

confidence: 99%

“…It is clear from these two papers that androgens can either promote or interfere with neuromuscular function, depending on other factors. Fargo and colleagues (Fargo et al, 2008) discuss perhaps two sides of the same coin-the role of androgens in promoting axonal growth after injury and how the partial loss of AR function in individuals that have SBMA may contribute to the loss of motor function caused by this disease. On the other hand, Monks and colleagues (2008) discuss possible mechanisms underlying SBMA, including the toxic role androgen itself plays in promoting neuromuscular demise in this disease.…”

Section: Role Of Ars In Neurodegeneration and Recovery Of Functionmentioning

confidence: 99%

“…A central goal since that time has been to determine the molecular mechanisms involved. They describe recent data from the Jones lab and the Poletti lab in both cell culture and in vivo approaches suggesting that androgens directly regulate expression of the neuritin gene to enhance axonal outgrowth (Fargo et al, 2008). For example, androgens can promote both neurite extension and expression of neuritin mRNA in cultured motoneuronlike cells that have been transfected with AR, but not in comparable cells that lack AR.…”

Section: Role Of Ars In Neurodegeneration and Recovery Of Functionmentioning

confidence: 99%

“…However, recent data suggest that the loss of AR function may also contribute to some of the pathology associated with this disease (Yu et al, 2006). Fargo et al (Fargo et al, 2008) hypothesize that the loss of AR function may also lead to a depletion of neuritin which could limit the motoneuron's ability to regenerate under pathological conditions. While a direct test of this hypothesis awaits investigation, the possibility that neuritin may be an effective therapeutic for SBMA is intriguing.…”

Section: Role Of Ars In Neurodegeneration and Recovery Of Functionmentioning

confidence: 99%

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Androgens in health and disease: An overview

Jordan

DonCarlos

2008

Hormones and Behavior

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This special issue of Hormones and Behavior, "Androgens in health and disease: new insights into roles and mechanisms of action," is prompted by a number of relatively recent findings that androgens affect brain morphology and function in ways not previously or widely appreciated. Moreover, recent results also make it clear that androgens utilize a variety of signaling molecules to exert their effects on the brain, which may or may not depend on the classic nuclear androgen receptor (AR). The papers in this issue underscore these two points. This overview is not intended as a comprehensive review of androgen action on the nervous system, since the papers in this issue serve that purpose, but rather to frame the basic issues and themes that tie these papers together. The sum effect of the stories told in this issue encourages us to broaden and refocus our view of androgen action on brain and behavior -to recognize that androgens affect many aspects of brain structure and function throughout the lifespan, from shaping its sexual phenotype to influencing its propensity for disease and repair, and that at least some of these actions are exerted via non-classical modes of action that in many cases were first identified in non-neural tissue or cells. Setting the stage: lessons from the periphery Sexual differentiation depends on testicular androgensPerhaps the first lesson that studies in the periphery taught us is that the same factors driving sexual differentiation of the periphery in mammals also drive sexual differentiation of the brain and behavior. What are these factors? Androgens produced and secreted by the testes. While the story is admittedly a bit more complicated than this, several decades of research support this basic tenet that testicular androgens critically mediate sexual differentiation of both the periphery and the brain and thus, behavior. Among the earlier work that was influential in giving rise to this basic tenet was that of Alfred Jost followed by the work of Phoenix, Goy, Gerall and Young.In the 1940s and 50s, Jost and colleagues carried out elegant experiments to identify the factors involved in sexual differentiation of the genital tract (Jost, 1953(Jost, , 1972. By studying the effects of removing the gonads from fetal rabbits and treating castrated fetuses with testosterone (T), Jost concluded that the testes and not the ovaries are responsible for sexual differentiation of the external genitalia, and that the testes exert their influence on genital differentiation by

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Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury

Byers

Huguenard

Kuruppu

et al. 2012

J of Comparative Neurology

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Treatment with testosterone is neuroprotective/neurotherapeutic after a variety of motoneuron injuries. Here we assessed whether testosterone might have similar beneficial effects after spinal cord injury (SCI). Young adult female rats received either sham or T9 spinal cord contusion injuries and were implanted with blank or testosterone-filled Silastic capsules. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross-sectional area, and motor endplate size and density. Contusion injury resulted in large lesions, with no significant differences in lesion volume, percent total volume of lesion, or spared white or gray matter between SCI groups. SCI with or without testosterone treatment also had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with testosterone. Similarly, the vastus lateralis muscle weights and fiber cross-sectional areas of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were both prevented by testosterone treatment. No effects on motor endplate area or density were observed across treatment groups. These findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be prevented by testosterone treatment, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system.

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Androgen regulation of axon growth and neurite extension in motoneurons

Cited by 51 publications

References 119 publications

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain

Handedness, motor skills and maturation of the corticospinal tract in the adolescent brain

Androgens in health and disease: An overview

Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury

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