Neuroprotective Effects of Progesterone in Chronic Experimental Autoimmune Encephalomyelitis

Giatti, Silvia; Caruso, Donatella; Boraso, Mariaserena; Abbiati, Federico; Ballarini, E; Calabrese, Donato; Pesaresi, Marzia; Rigolio, R; Santos-Galindo, María; Viviani, Bárbara; Cavaletti, Guido; García‐Segura, Luis M.; Melcangi, Roberto Cosimo

doi:10.1111/j.1365-2826.2012.02284.x

Cited by 52 publications

(43 citation statements)

References 75 publications

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“…A similar pattern was detected for MHC-II staining. As already described in our previous observations [24,35] , MHC-II-immunoreactive cells were increased in the spinal cord of vehicle-treated EAE DA rats compared to control animals ( fig. 3 a-d).…”

Section: Inflammatory Parameterssupporting

confidence: 68%

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: Inflammatory Parameterssupporting

confidence: 68%

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

et al. 2015

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“…In the same animal model, other evidences report that PROG was able to reduce inflammatory markers (i.e. microglia activation, IL1b, IL2, and IL17) (Yates et al 2010, Giatti et al 2012.…”

Section: Neuroactive Steroids As Neuroinflammatory Modulatorsmentioning

confidence: 98%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

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“…[9][10][11][12][63][64][65][66][67] We have demonstrated in previous works that chronic PROG administration increases the expression of transcription factors that define oligodendrocyte linage, such as Olig2 and Nkx2.2 after spinal cord transection. 21,29 In the present work, we report that PROG treatment reduced the loss of oligodendrocyte numbers and MBP immunoreactivity produced by SCI.…”

Section: Prog Reduced Secondary Injury and White Matter Pathologymentioning

confidence: 99%

“…7,8 Progesterone (PROG) could represent a good candidate for therapy, because it is neuroprotective, promyelinating, and antiinflammatory in pathologies of peripheral and central nervous systems. [9][10][11][12] Specifically, in experimental brain trauma, PROG reduces edema and inflammatory cytokines, prevents neuronal loss and mitochondrial dysfunction, and improves functional outcomes. [13][14][15] This has permitted the development of two Phase II clinical trials that have recently shown significant improvements in patients with traumatic brain injury receiving PROG.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

Garcı́a-Ovejero

GonzálezSusana²,

Paniagua-TorijaBeatriz³

et al. 2014

Journal of Neurotrauma

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Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury.

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Neuroprotective Effects of Progesterone in Chronic Experimental Autoimmune Encephalomyelitis

Cited by 52 publications

References 75 publications

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Neuroactive steroids, their metabolites, and neuroinflammation

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

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