Neuroactive Steroids: A Therapeutic Approach to Maintain Peripheral Nerve Integrity During Neurodegenerative Events

Leonelli, Emanuela; Ballabio, M.; Consoli, Antonio; Roglio, Ilaria; Magnaghi, Valerio; Melcangi, Roberto Cosimo

doi:10.1385/jmn:28:1:65

Cited by 25 publications

(20 citation statements)

References 94 publications

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“…Central and peripheral nerve systems are targets for steroid hormones, where they regulate important nerve functions. Progesterone has been shown to promote myelination of nerve structures and thus protect them against neurodegenerative events due to physical trauma, invasion and aging processes [37]. Estrogens seem to improve sympathetic innervation, as has been demonstrated in animal models [36].…”

Section: Discussionmentioning

confidence: 99%

Increased Nerve Density in Deep Infiltrating Endometriotic Nodules

Anaf¹,

Nakadi

Moor

et al. 2010

Gynecol Obstet Invest

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Background/Aims: Deep infiltrating endometriosis is a very painful condition and the mechanism of pain is still poorly understood. Pain and hyperalgesia can partly be explained by an increased number of nerve structures in the painful lesion. In order to clarify this issue, we assessed the nerve density in deep infiltrating endometriotic nodules of the posterior vagina and in the adjacent healthy vaginal tissue of the same patient. Methods: A prospective clinical and pathological study of 31 cases of deep infiltrating vaginal endometriotic nodules was conducted. Fifteen patients were in the proliferative phase and 16 in the secretory phase. The nerve density was studied by immunohistochemistry with the monoclonal antibody NF against neurofilaments in deep infiltrating endometriosis and in the adjacent unaffected vaginal tissue in the proliferative and in the secretory phases. Neurofilaments constitute the main structural elements of neuronal axons and dendrites. Results: The nerve density was significantly different in the endometriotic nodule than in the adjacent unaffected vaginal tissue (p = 0.0013). The same significant difference was found between endometriotic nodules and the unaffected vagina in the proliferative phase (p = 0.009) and in the secretory phase (p = 0.04). This difference was not significant between the proliferative and the secretory phases in the endometriotic lesions and in the controls. Conclusions: We hypothesize that the significantly increased number of nerve structures in the endometriotic nodules may contribute to the occurrence of severe and neuropathic pain that characterizes these lesions

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Section: Discussionmentioning

confidence: 99%

Increased Nerve Density in Deep Infiltrating Endometriotic Nodules

Anaf¹,

Nakadi

Moor

et al. 2010

Gynecol Obstet Invest

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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: 95%

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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“…In the PNS, PROG promotes synthesis of the myelin proteins Po and PMP22 and increases the transcription factors Krox-20 and Sox-10 by Schwann cells (Desarnaud et al, 1998;Guennoun et al, 2001;Koenig et al, 1995;Magnaghi et al, 2006Magnaghi et al, , 2007. PROG and its metabolites also prevent myelin alterations of diabetic neuropathy and maintain integrity of peripheral nerves during neurodegeneration and aging (Azcoitia et al, 2003;Leonelli et al, 2006;Veiga et al, 2006). In the CNS, PROG increases the expression of MBP and the mature oligodendrocyte marker cyclic nucleotide 3 0 -phosphodieterase (CNPase) in cultures of mixed glial cells and organotypic slice cultures of cerebellum (Ghoumari et al, 2003;JungTestas et al, 1996); besides, PROG induces remyelination after toxin-induced lesions of the cerebellar peduncle of aging rats (Ibanez et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of progesterone on oligodendrocyte progenitors, oligodendrocyte transcription factors, and myelin proteins following spinal cord injury

Labombarda

González

Lima

et al. 2008

Glia

101

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Progesterone is emerging as a myelinizing factor for central nervous system injury. Successful remyelination requires proliferation and differentiation of oligodendrocyte precursor cells (OPC) into myelinating oligodendrocytes, but this process is incomplete following injury. To study progesterone actions on remyelination, we administered progesterone (16 mg/kg/day) to rats with complete spinal cord injury. Rats were euthanized 3 or 21 days after steroid treatment. Short progesterone treatment (a) increased the number of OPC without effect on the injury-induced reduction of mature oligodendrocytes, (b) increased mRNA and protein expression for the myelin basic protein (MBP) without effects on proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), and (c) increased the mRNA for Olig2 and Nkx2.2 transcription factors involved in specification and differentiation of the oligodendrocyte lineage. Furthermore, long progesterone treatment (a) reduced OPC with a concomitant increase of oligodendrocytes; (b) promoted differentiation of cells that incorporated bromodeoxyuridine, early after injury, into mature oligodendrocytes; (c) increased mRNA and protein expression of PLP without effects on MBP or MOG; and (d) increased mRNA for the Olig1 transcription factor involved in myelin repair. These results suggest that early progesterone treatment enhanced the density of OPC and induced their differentiation into mature oligodendrocytes by increasing the expression of Olig2 and Nkx2.2. Twenty-one days after injury, progesterone favors remyelination by increasing Olig1 (involved in repair of demyelinated lesions), PLP expression, and enhancing oligodendrocytes maturation. Thus, progesterone effects on oligodendrogenesis and myelin proteins may constitute fundamental steps for repairing traumatic injury inflicted to the spinal cord.

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Neuroactive Steroids: A Therapeutic Approach to Maintain Peripheral Nerve Integrity During Neurodegenerative Events

Cited by 25 publications

References 94 publications

Increased Nerve Density in Deep Infiltrating Endometriotic Nodules

Increased Nerve Density in Deep Infiltrating Endometriotic Nodules

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

Effects of progesterone on oligodendrocyte progenitors, oligodendrocyte transcription factors, and myelin proteins following spinal cord injury

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