Neuroactive steroids and peripheral myelin proteins

Magnaghi, Valerio; Cavarretta, Ilaria T.; Galbiati, M.; Martini, L.; Melcangi, Roberto Cosimo

doi:10.1016/s0165-0173(01)00140-0

Cited by 109 publications

(101 citation statements)

References 48 publications

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“…In addition, progesterone increased expression of its receptor and of myelin proteins in co-cultured dorsal root ganglial neurons, but did not increase expression or nuclear localization of the progesterone receptor in Schwann cells . Neither progesterone nor RU-486 affected expression of progesterone receptor mRNA in Schwann cell cultures, suggesting that effects of progesterone on Schwann cells may be mediated through other receptors, or may be mediated through metabolism to other neurosteroids such as allopregnanolone (Magnaghi et al, 2006;Magnaghi et al, 2001). Thus, progesterone affects myelin synthesis directly in Schwann cells as well as indirectly through induction of gene expression in neurons.…”

Section: Myelinationmentioning

confidence: 97%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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Section: Myelinationmentioning

confidence: 97%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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“…These two receptor systems are involved in the expression of distinct major peripheral myelin proteins, namely, protein zero (P0) and peripheral myelin protein 22 (PMP22). PROG and 5␣-dihydroprogesterone, which both bind with high affinity to the intracellular PR, increase expression of P0 expression via this receptor, whereas 3␣,5␣-TH PROG increases PMP22 expression by modulating Schwann cell GABA A receptors Magnaghi et al, 2001). Both P0 and PMP22 are encoded by dosage-sensitive genes and are major culprits in motor and sensory neuropathies, which show an increased frequency in the elderly (Suter and Snipes, 1995;Suter and Nave, 1999).…”

Section: Pleiotropic Effects Of Steroids In the Nervous System With Smentioning

confidence: 99%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

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Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the ␤-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to 5-androstene-3␤,17␤-diol and to 7␣-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of ␤-amyloid deposits.

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“…Past reports find that administration of P 4 with E 2 to OVX rats, increases hippocampal spine density (Woolley et al 1996, Miranda et al 1999 and some of these effects are likely due to actions through its metabolism to 3a,5a-THP. In support, 3a,5a-THP has trophic effects to enhance central and peripheral myelination, it is neuroprotective in traumatic brain injury and ischemic stroke, and improves functional outcome after trauma (Magnaghi et al 2001, Schumacher et al 2001, Ghoumari et al 2003, Sayeed et al 2006, VanLandingham et al 2007). As such, trophic effects of 3a,5a-THP may underlie some of the neuroprotective aspects that have been reported with motherhood in aging (Gatewood et al 2005, Pawluski & Galea 2007.…”

mentioning

confidence: 94%

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

Paris¹,

Frye²

2008

Reproduction

116

105

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Ovarian hormone elevations are associated with enhanced learning/memory. During behavioral estrus or pregnancy, progestins, such as progesterone (P 4 ) and its metabolite 5a-pregnan-3a-ol-20-one (3a,5a-THP), are elevated due, in part, to corpora luteal and placental secretion. During 'pseudopregnancy', the induction of corpora luteal functioning results in a hormonal milieu analogous to pregnancy, which ceases after about 12 days, due to the lack of placental formation. Multiparity is also associated with enhanced learning/memory, perhaps due to prior steroid exposure during pregnancy. Given evidence that progestins and/or parity may influence cognition, we investigated how natural alterations in the progestin milieu influence cognitive performance. In Experiment 1, virgin rats (nulliparous) or rats with two prior pregnancies (multiparous) were assessed on the object placement and recognition tasks, when in high-estrogen/P 4 (behavioral estrus) or low-estrogen/P 4 (diestrus) phases of the estrous cycle. In Experiment 2, primiparous or multiparous rats were tested in the object placement and recognition tasks when not pregnant, pseudopregnant, or pregnant (between gestational days (GDs) 6 and 12). In Experiment 3, pregnant primiparous or multiparous rats were assessed daily in the object placement or recognition tasks. Females in natural states associated with higher endogenous progestins (behavioral estrus, pregnancy, multiparity) outperformed rats in low progestin states (diestrus, non-pregnancy, nulliparity) on the object placement and recognition tasks. In earlier pregnancy, multiparous, compared with primiparous, rats had a lower corticosterone, but higher estrogen levels, concomitant with better object placement performance. From GD 13 until post partum, primiparous rats had higher 3a,5a-THP levels and improved object placement performance compared with multiparous rats.

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Neuroactive steroids and peripheral myelin proteins

Cited by 109 publications

References 48 publications

Neurosteroid regulation of central nervous system development

Neurosteroid regulation of central nervous system development

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks

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