Neuroprotective actions of androgens on motoneurons

Fargo, Keith N.; Foecking, Eileen M.; Jones, Kathryn J.; Sengelaub, Dale R.

doi:10.1016/j.yfrne.2009.04.005

Cited by 66 publications

(51 citation statements)

References 159 publications

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“…Thus, the results reported here suggest protective effects after DHT treatment on chronic EAE, proposing a therapeutic potential for this neuroactive steroid. Previous observations obtained in other experimental models of neurodegeneration described protective [40][41][42][43] or detrimental effects after DHT treatment [44,45] . Moreover, controversial results were also reported in models of MS [16][17][18]23] .…”

Section: Discussionmentioning

confidence: 72%

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

et al. 2015

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Multiple sclerosis is a chronic inflammatory disease affecting the central nervous system. As reported by clinical observations, variation in hormonal levels might alter disease susceptibility and progression. Specifically, decreased levels of testosterone in males are reported to be permissive for disease onset. Accordingly, testosterone seems to exert protective effects in experimental autoimmune encephalomyelitis (EAE). In this context, it is important to highlight that testosterone is further metabolized into 17ß-estradiol or dihydrotestosterone (DHT). In this study, we aimed to explore the protective effects of DHT treatment in EAE Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction showed that DHT exerts a beneficial effect on clinical scores, coupled with decreased gliosis (i.e. glial fibrillary acidic protein and major histocompatibility complex of class II staining) and inflammation (i.e. translocator protein 18 kDa, interleukin-1ß, Toll-like receptor 4 and nuclear factor-κB expression) in the spinal cord. Moreover, parameters linked to oxidative stress and tissue damage, like thiobarbituric acid-reactive substance levels and Bcl-2-associated X protein expression, and to mitochondrial activity (i.e. content of mitochondrial DNA and proteins), were improved after DHT administration. This neuroactive steroid may be further metabolized into 3a- or 3ß-diol. However, assessment of the levels of these metabolites after DHT treatment seems to suggest that the protective effects observed here are due to DHT itself. Altogether, the present results indicate that DHT was effective in reducing the severity of chronic EAE and, consequently, may represent an interesting perspective for multiple sclerosis treatment.

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Section: Discussionmentioning

confidence: 72%

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

et al. 2015

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“…In addition, new experimental data, showing that a prolonged period of hypoestrogenicity disrupts both neuroprotective and anti-inflammatory actions of estradiol [11], may help to reconcile the results of animal studies with those of the WHIMS. Some clinical evidence also supports the potential cognitive benefit of testosterone therapy in men [8] and several experimental studies have identified neuroprotective actions of adrenal and testicular androgens [5,8]. However, it is clear that we need more basic information on the mechanisms involved in the neuroprotective actions of steroids to predict the conditions in which hormone treatments may have positive outcomes for brain function in humans and design the best possible therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Steroids and neuroprotection: New advances

Garcia-Segura

Balthazart

2009

Frontiers in Neuroendocrinology

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Gonadal hormones exert neuroprotective actions. In addition, it has become evident that the local synthesis of these molecules in the central nervous system may prevent or reduce neurodegeneration. The neuroprotective actions of steroids involve neurons, glial cells and blood vessels, are exerted via steroid receptor signaling initiated at the nuclear or membrane level and steroid receptor independent mechanisms. They include the regulation of phosphatases and kinases and the regulation of the expression of molecules controlling inflammation and apoptosis. In addition, mitochondria have emerged as new central targets for neuroprotective actions of steroids. These neuroprotective actions have been documented in different experimental models of neurological alterations, including motoneuron injury, Parkinson’s disease, traumatic brain injury, multiple sclerosis, stroke and Alzheimer’s disease. In addition, steroids promote serotonergic neuronal function and protect against affective disorders. This special issue of Frontiers in Neuroendocrinology contains a collection of reviews of the most recent ideas and findings on these various aspects of sex steroid-dependent neuroprotection.

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“…Androgens exhibit a wide array of neuroprotective and neurotherapeutic effects in motoneurons [8]. Our previous studies have demonstrated that testosterone is neuroprotective following motoneuron loss.…”

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confidence: 99%

“…Androgens have robust neuroprotective effects on motoneurons, mediating a variety of cellular and molecular mechanisms [8]. Establishing which of these mechanisms, proteins, and pathways are involved in the androgen-mediated protection of motoneuron dendrites from injury-induced atrophy will be valuable contributions to establishing new neurotherapeutic strategies.…”

mentioning

confidence: 99%

Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: Efficacy in female rats

Wilson

Coons

Sengelaub

2009

Neuroscience Letters

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Motoneuron loss is a significant medical problem, capable of causing severe movement disorders and even death. We have previously demonstrated that partial depletion of motoneurons induces dendritic atrophy in remaining motoneurons, with a concomitant reduction in motor activation. Treatment of male rats with testosterone attenuates the regressive changes following partial motoneuron depletion. To test whether testosterone has similar effects in females, we examined potential neuroprotective effects in motoneurons innervating muscles of the quadriceps of female rats. Motoneurons were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were given implants containing testosterone or left untreated. Four weeks later, surviving motoneurons were labeled with cholera toxin-conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Compared to normal females, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons, and this atrophy was greatly attenuated by testosterone treatment. These findings suggest that testosterone has neuroprotective effects on morphology in both males and females, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system. Keywords steroids; neuroprotection; morphology; dendrites Motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (e.g., spinal and bulbar muscular atrophy) are characterized by progressive loss of motoneurons [3,17]. Similarly, damage to spinal nerves resulting in laceration and avulsion of spinal roots can lead to the death of motoneurons and preganglionic autonomic neurons in the spinal cord, resulting in autonomic and motor dysfunction [16]. However, the death of motoneurons is not the only outcome, and after such insults surviving motoneurons undergo dendritic retraction and atrophy [e.g., 2,28] as well as functional and biochemical changes [e.g., 1,33]. We have been examining the effects of motoneuron loss on the structure and function of surviving motoneurons using a rat model of motoneuron death. Partial depletion of motoneurons results in substantial somal and dendritic atrophy [10][11][12]23] and reduced excitability [9,23] in the remaining motoneurons.

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Neuroprotective actions of androgens on motoneurons

Cited by 66 publications

References 159 publications

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Steroids and neuroprotection: New advances

Neuroprotective effects of testosterone on dendritic morphology following partial motoneuron depletion: Efficacy in female rats

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