Neuroactive Steroid Levels in a Transgenic Rat Model of CMT1A Neuropathy

Caruso, Donatella; Scurati, Silvia; Roglio, Ilaria; Nobbio, Lucilla; Schenone, Angelo; Melcangi, Roberto Cosimo

doi:10.1007/s12031-007-9029-3

Cited by 34 publications

(29 citation statements)

References 30 publications

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“…This is in agreement with the general decrease of neuroactive steroid levels observed in different animal models of neurodegeneration, such as Parkinson's disease, multiple sclerosis, peripheral neuropathies and diabetic encephalopathy [31,171,[183][184][185][186][187][188][189][190][191][192][193].…”

Section: Effects Of 5α-ri Therapy On Neurobehavioral Functions and Nesupporting

confidence: 84%

Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

Traish

Melcangi

Bortolato

et al. 2015

Rev Endocr Metab Disord

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Steroids are important physiological orchestrators of endocrine as well as peripheral and central nervous system functions. One of the key processes for regulation of these molecules lies in their enzymatic processing by a family of 5α-reductase (5α-Rs) isozymes. By catalyzing a key rate-limiting step in steroidogenesis, this family of enzymes exerts a crucial role not only in the physiological control but also in pathological events. Indeed, both 5α-R inhibition and supplementation of 5α-reduced metabolites are currently used or have been proposed as therapeutic strategies for a wide array of pathological conditions. In particular, the potent 5α-R inhibitors finasteride and dutasteride are used in the treatments of benign prostatic hyperplasia (BPH), as well as in male pattern hair loss (MPHL) known as androgenetic alopecia (AGA). Recent preclinical and clinical findings indicate that 5α-R inhibitors evoke not only beneficial, but also adverse effects. Future studies should investigate the biochemical and physiological mechanisms that underlie the persistence of the adverse sexual side effects to determine why a subset of patients is afflicted with such persistence or irreversible adverse effects. Also a better focus of clinical research is urgently needed to better define those subjects who are likely to be adversely affected by such agents. Furthermore, research on the non-sexual adverse effects such as diabetes, psychosis, depression, and cognitive function are needed to better understand the broad spectrum of the effects these drugs may elicit during their use in treatment of AGA or BPH. In this review, we will summarize the state of art on this topic, overview the key unresolved questions that have emerged on the pharmacological targeting of these enzymes and their products, and highlight the need for further studies to ascertain the severity and duration of the adverse effects of 5α-R inhibitors, as well as their biological underpinnings.

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Section: Effects Of 5α-ri Therapy On Neurobehavioral Functions and Nesupporting

confidence: 84%

Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

Traish

Melcangi

Bortolato

et al. 2015

Rev Endocr Metab Disord

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“…Investigating neuroactive steroid changes directly in the CNS, particularly under experimental conditions replicating specific neurological conditions, may be of vital importance to set the ground for specific therapeutic approaches based on these agents. We have recently applied the assessment of neuroactive steroids, by liquid chromatography tandem mass spectrometry (LC-MS/MS), in different experimental models of neurodegeneration, observing that their levels are affected by the neuronal pathology (Caruso et al 2008a;Caruso et al 2008b;Caruso et al 2010;Giatti et al 2010;Melcangi and Garcia-Segura 2010;Pesaresi et al 2010). However, scarce information has been so far obtained in PD.…”

Section: Introductionmentioning

confidence: 99%

Modifications of Neuroactive Steroid Levels in an Experimental Model of Nigrostriatal Degeneration: Potential Relevance to the Pathophysiology of Parkinson’s Disease

et al. 2011

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An important link between neuroactive steroids and neurodegenerative disorders has recently been suggested. Indeed, in several neurodegenerative experimental models the levels of neuroactive steroids are affected and their administration exerts neuroprotective effects. However, scarce information has so far been obtained on the neuroactive steroid levels present in Parkinson's disease. To this aim, using an experimental model of loss of nigrostriatal dopaminergic neurons obtained by stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA), we evaluated by liquid chromatography tandem mass spectrometry the levels of several neuroactive steroids in the striatum and cerebral cortex of 6-OHDA-lesioned male rats. Among the neuroactive steroid levels assessed (i.e., pregnenolone, progesterone, dihydroprogesterone, tetrahydroprogesterone, isopregnanolone, testosterone, dihydrotestosterone, 3α-diol, dehydroepiandrosterone, 17α-estradiol, and 17β-estradiol), we observed a significant decrease of pregnenolone in the striatum. A similar effect was also observed on the levels of dihydroprogesterone present in this cerebral area and also in the cerebral cortex. Interestingly, an increase of isopregnanolone also occurred in the striatum and in the cerebral cortex. Altogether, these results suggesting that progesterone metabolism is affected in an experimental model of Parkinson's disease further highlight the link between neuroactive steroids and the neurodegenerative diseases.

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“…As reported, women show higher disability than men [100], association of restless legs syndrome and polyneuropathy, as well as sensory neuropathy of small fiber type [101]. Data obtained in an experimental model of CMT1A have shown that the levels of isopregnanolone are decreased only in female sciatic nerve, while those of 3a-diol are decreased in only male [49].…”

Section: May Neuroactive Steroids Be the Basis Of Sex-oriented Treatmmentioning

confidence: 80%

“…Indeed, as demonstrated in experimental models and clinical studies, neurodegenerative and psychiatric disorders affect neuroactive steroid levels [13,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. For instance, neuroactive steroid levels are modified in experimental models of acquired peripheral neuropathy, such as those due to trauma [68] or diabetes [50,61] and inherited peripheral neuropathy (e.g., Charcot-Marie-Tooth type 1A, CMT1A) [49]. Pathological conditions also modified neuroactive steroid levels in CNS.…”

Section: Neural Pathology Influences Neuroactive Steroid Levelsmentioning

confidence: 99%