Allopregnanolone: State of the art

Adeosun, 2012, Allopregnanolone reinstates tyrosine hydroxylase immunoreactive neurons and motor performance in an MPTP-lesioned mouse model of Parkinson's disease, PLoS One, 7, e50040, 10.1371/journal.pone.0050040 Ahmad, 2005, Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann–Pick C mice, J. Neurosci. Res., 82, 811, 10.1002/jnr.20685 Azcoitia, 2003, Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats, Neurobiol. Aging, 24, 853, 10.1016/S0197-4580(02)00234-8 Backstrom, 2013, Allopregnanolone and mood disorders, Prog. Neurobiol. Backstrom, 2005, Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats, Eur. J. Pharmacol., 512, 15, 10.1016/j.ejphar.2005.01.049 Banks, 1980, Inhibition of the daily LH release mechanism by progesterone acting at the hypothalamus, Biol. Reprod., 22, 217, 10.1095/biolreprod22.2.217 Barraclough, 1986, Stimulatory versus inhibitory effects of progesterone on estrogen-induced phasic LH and prolactin secretion correlated with estrogen nuclear and progestin cytosol receptor concentrations in brain and pituitary gland, Neuroendocrinology, 42, 6, 10.1159/000124241 Barron, 2013, Ligand for translocator protein reverses pathology in a mouse model of Alzheimer's disease, J. Neurosci., 33, 8891, 10.1523/JNEUROSCI.1350-13.2013 Beckley, 2008, Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female withdrawal seizure-prone vs withdrawal seizure-resistant mice, Neuropharmacology, 54, 365, 10.1016/j.neuropharm.2007.10.006 Belelli, 1989, Anticonvulsant profile of the progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one, Eur. J. Pharmacol., 166, 325, 10.1016/0014-2999(89)90077-0 Belelli, 2005, Neurosteroids: endogenous regulators of the GABA(A) receptor, Nat. Rev. Neurosci., 6, 565, 10.1038/nrn1703 Biggio, 2009, GABA(A) receptor function and gene expression during pregnancy and postpartum, Int. Rev. Neurobiol., 85, 73, 10.1016/S0074-7742(09)85006-X Bitran, 1991, Anxiolytic effects of 3 alpha-hydroxy-5 alpha[beta]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor, Brain Res., 561, 157, 10.1016/0006-8993(91)90761-J Bourque, 2009, Neuroprotective actions of sex steroids in Parkinson's disease, Front. Neuroendocrinol., 30, 142, 10.1016/j.yfrne.2009.04.014 Brann, 1991, Regulation of gonadotropin secretion by steroid hormones, Front. Neuroendocrinol., 12, 165 Brinton, 2013, Neurosteroids as regenerative agents in the brain: therapeutic implications, Nat. Rev. Endocrinol., 9, 241, 10.1038/nrendo.2013.31 Brunton, 2013, Allopregnanolone in the brain: protecting pregnancy and birth outcomes, Prog. Neurobiol. Callier, 2001, Neuroprotective properties of 17beta-estradiol, progesterone, and raloxifene in MPTP C57Bl/6 mice, Synapse, 41, 131, 10.1002/syn.1067 Caruso, 2013, Age-related changes in neuroactive steroid levels in 3xTg-AD mice, Neurobiol. Aging, 34, 1080, 10.1016/j.neurobiolaging.2012.10.007 Caruso, 2010, Sex-dimorphic changes in neuroactive steroid levels after chronic experimental autoimmune encephalomyelitis, J. Neurochem., 114, 921, 10.1111/j.1471-4159.2010.06825.x Caruso, 2010, Effects of short- and long-term gonadectomy on neuroactive steroid levels in the central and peripheral nervous system of male and female rats, J. Neuroendocrinol., 22, 1137, 10.1111/j.1365-2826.2010.02064.x Caruso, 2008, Evaluation of neuroactive steroid levels by liquid chromatography–tandem mass spectrometry in central and peripheral nervous system: effect of diabetes, Neurochem. Int., 52, 560, 10.1016/j.neuint.2007.06.004 Caruso, 2008, Neuroactive steroid levels in a transgenic rat model of CMT1A neuropathy, J. Mol. Neurosci., 34, 249, 10.1007/s12031-007-9029-3 Cermenati, 2013, Liver X receptors, nervous system, and lipid metabolism, J. Endocrinol. Invest., 36, 435 Cermenati, 2010, Activation of the liver X receptor increases neuroactive steroid levels and protects from diabetes-induced peripheral neuropathy, J. Neurosci., 30, 11896, 10.1523/JNEUROSCI.1898-10.2010 Chan, 1998, Glucocorticoids and progestins signal the initiation and enhance the rate of myelin formation, Proc. Natl. Acad. Sci. USA, 95, 10459, 10.1073/pnas.95.18.10459 Chan, 2000, Progesterone synthesized by Schwann cells during myelin formation regulates neuronal gene expression, Mol. Biol. Cell, 11, 2283, 10.1091/mbc.11.7.2283 Chen, 2011, Allopregnanolone promotes regeneration and reduces beta-amyloid burden in a preclinical model of Alzheimer's disease, PLoS One, 6, e24293, 10.1371/journal.pone.0024293 Ciriza, 2004, Reduced progesterone metabolites protect rat hippocampal neurones from kainic acid excitotoxicity in vivo, J. Neuroendocrinol., 16, 58, 10.1111/j.1365-2826.2004.01121.x Ciriza, 2006, Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus, the synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective, J. Neurobiol., 66, 916, 10.1002/neu.20293 Corpechot, 1981, Characterization and measurement of dehydroepiandrosterone sulfate in rat brain, Proc. Natl. Acad. Sci. USA, 78, 4704, 10.1073/pnas.78.8.4704 Czlonkowska, 2000, The effects of neurosteroids on picrotoxin-, bicuculline- and NMDA-induced seizures, and a hypnotic effect of ethanol, Pharmacol. Biochem. Behav., 67, 345, 10.1016/S0091-3057(00)00369-5 Darbra, 2013, Neonatal allopregnanolone levels alteration: effects on behavior and role of the hippocampus, Prog. Neurobiol. Daugherty, 2013, A TSPO ligand is protective in a mouse model of multiple sclerosis, EMBO Mol. Med., 5, 891, 10.1002/emmm.201202124 Djebaili, 2004, Allopregnanolone and progesterone decrease cell death and cognitive deficits after a contusion of the rat pre-frontal cortex, Neuroscience, 123, 349, 10.1016/j.neuroscience.2003.09.023 Eser, 2008, Neuroactive steroids as endogenous modulators of anxiety, Curr. Pharm. Des., 14, 3525, 10.2174/138161208786848838 Ficher, 1971, In vitro progesterone metabolism by rat testicular tissue at different stages of development, Acta Endocrinol. (Copenh.), 68, 285, 10.1530/acta.0.0680285 Frye, 2000, Anti-seizure effects of progesterone and 3alpha, 5alpha-THP in kainic acid and perforant pathway models of epilepsy, Psychoneuroendocrinology, 25, 407, 10.1016/S0306-4530(99)00068-2 Garay, 2007, Effects of progesterone in the spinal cord of a mouse model of multiple sclerosis, J. Steroid Biochem. Mol. Biol., 107, 228, 10.1016/j.jsbmb.2007.03.040 Garay, 2009, Protective effects of progesterone administration on axonal pathology in mice with experimental autoimmune encephalomyelitis, Brain Res., 1283, 177, 10.1016/j.brainres.2009.04.057 Garcia-Segura, 1994, Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus, Glia, 10, 59, 10.1002/glia.440100108 Ghoumari, 2005, Progesterone increases oligodendroglial cell proliferation in rat cerebellar slice cultures, Neuroscience, 135, 47, 10.1016/j.neuroscience.2005.05.023 Ghoumari, 2003, Progesterone and its metabolites increase myelin basic protein expression in organotypic slice cultures of rat cerebellum, J. Neurochem., 86, 848, 10.1046/j.1471-4159.2003.01881.x Giachino, 2003, Neurogenesis in the subependymal layer of the adult rat: a role for neuroactive derivatives of progesterone, Ann. N. Y. Acad. Sci., 1007, 335, 10.1196/annals.1286.032 Giatti, 2012, Neuroprotective effects of progesterone in chronic experimental autoimmune encephalomyelitis, J. Neuroendocrinol., 24, 851, 10.1111/j.1365-2826.2012.02284.x Giatti, 2010, Acute experimental autoimmune encephalomyelitis induces sex dimorphic changes in neuroactive steroid levels, Neurochem. Int., 56, 118, 10.1016/j.neuint.2009.09.009 Giatti, 2009, Neuroprotective effects of a ligand of translocator protein-18kDa (Ro5-4864) in experimental diabetic neuropathy, Neuroscience, 164, 520, 10.1016/j.neuroscience.2009.08.005 Girard, 2008, Etifoxine improves peripheral nerve regeneration and functional recovery, Proc. Natl. Acad. Sci. USA, 105, 20505, 10.1073/pnas.0811201106 Girard, 2009, Preventive and curative effects of etifoxine in a rat model of brain oedema, Clin. Exp. Pharmacol. Physiol., 36, 655, 10.1111/j.1440-1681.2008.05127.x Girdler, 2007, Neurosteroids in the context of stress: implications for depressive disorders, Pharmacol. Ther., 116, 125, 10.1016/j.pharmthera.2007.05.006 Griffin, 2004, Niemann–Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone, Nat. Med., 10, 704, 10.1038/nm1073 Grobin, 2001, 3Alpha-hydroxy-5alpha-pregnan-20-one levels and GABA(A) receptor-mediated 36Cl(−) flux across development in rat cerebral cortex, Dev. Brain Res., 131, 31, 10.1016/S0165-3806(01)00242-5 He, 2004, Progesterone and allopregnanolone reduce inflammatory cytokines after traumatic brain injury, Exp. Neurol., 189, 404, 10.1016/j.expneurol.2004.06.008 Hovakimyan, 2013, Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann–Pick type C1 mice, Neuroscience, 252, 201, 10.1016/j.neuroscience.2013.08.001 Ibanez, 2003, Steroids and the reversal of age-associated changes in myelination and remyelination, Prog. Neurobiol., 71, 49, 10.1016/j.pneurobio.2003.09.002 Ishrat, 2010, Progesterone and allopregnanolone attenuate blood–brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases, Exp. Neurol., 226, 183, 10.1016/j.expneurol.2010.08.023 Irwin, 2013, Allopregnanolone as regenerative therapeutic for Alzheimer's disease: translational development and clinical promise, Prog. Neurobiol. Kawano, 2011, Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats, J. Anesth., 25, 942, 10.1007/s00540-011-1216-2 Labombarda, 2013, Neuroprotection by steroids after neurotrauma in organotypic spinal cord cultures: a key role for progesterone receptors and steroidal modulators of GABAA receptors, Neuropharmacology, 71, 46, 10.1016/j.neuropharm.2013.03.010 Labombarda, 2006, Injury elicited increase in spinal cord neurosteroid content analyzed by gas chromatography mass spectrometry, Endocrinology, 147, 1847, 10.1210/en.2005-0955 Lambert, 2003, Neurosteroid modulation of GABAA receptors, Prog. Neurobiol., 71, 67, 10.1016/j.pneurobio.2003.09.001 Leonelli, 2007, Progesterone and its derivatives are neuroprotective agents in experimental diabetic neuropathy: a multimodal analysis, Neuroscience, 144, 1293, 10.1016/j.neuroscience.2006.11.014 Leonelli, 2005, Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats, Mech. Ageing Dev., 126, 1159, 10.1016/j.mad.2005.06.001 Liao, 2009, Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1−/− mouse brain, Brain Res., 1270, 140, 10.1016/j.brainres.2009.03.027 Lonsdale, 2007, The anticonvulsant effects of allopregnanolone against amygdala-kindled seizures in female rats, Neurosci. Lett., 411, 147, 10.1016/j.neulet.2006.10.023 Lonsdale, 2006, The anticonvulsant effects of progesterone and its metabolites on amygdala-kindled seizures in male rats, Brain Res., 1101, 110, 10.1016/j.brainres.2006.05.005 Luquin, 1993, Natural fluctuation and gonadal hormone regulation of astrocyte immunoreactivity in dentate gyrus, J. Neurobiol., 24, 913, 10.1002/neu.480240705 Meffre, 2007, Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: analysis by gas chromatography/mass spectrometry, Endocrinology, 148, 2505, 10.1210/en.2006-1678 Melcangi, 2003, Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves, Prog. Neurobiol., 71, 57, 10.1016/j.pneurobio.2003.09.003 Melcangi, 2012, Modifications of neuroactive steroid levels in an experimental model of nigrostriatal degeneration: potential relevance to the pathophysiology of Parkinson's disease, J. Mol. Neurosci., 46, 177, 10.1007/s12031-011-9570-y Melcangi, 2010, Sex-specific therapeutic strategies based on neuroactive steroids: in search for innovative tools for neuroprotection, Horm. Behav., 57, 2, 10.1016/j.yhbeh.2009.06.001 Melcangi, 2008, Neuroactive steroids: state of the art and new perspectives, Cell Mol. Life Sci., 65, 777, 10.1007/s00018-007-7403-5 Melcangi, 2013, Levels and actions of progesterone and its metabolites in the nervous system during physiological and pathological conditions, Prog. Neurobiol. Melcangi, 2011, Role of neuroactive steroids in the peripheral nervous system, Front. Endocrinol. (Lausanne), 2, 104, 10.3389/fendo.2011.00104 Melcangi, 2011, Neuroactive steroids: focus on human brain, Neuroscience, 191, 1, 10.1016/j.neuroscience.2011.06.024 Meyer, 2010, Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy-induced painful neuropathy, Cell Mol. Life Sci., 67, 3017, 10.1007/s00018-010-0372-0 Meyer, 2011, Allopregnanolone prevents and suppresses oxaliplatin-evoked painful neuropathy: multi-parametric assessment and direct evidence, Pain, 152, 170, 10.1016/j.pain.2010.10.015 Micevych, 2008, Synthesis and function of hypothalamic neuroprogesterone in reproduction, Endocrinology, 149, 2739, 10.1210/en.2008-0011 Micevych, 2011, The neurosteroid progesterone underlies estrogen positive feedback of the LH surge, Front. Endocrinol. (Lausanne), 2, 90, 10.3389/fendo.2011.00090 Mitro, 2012, LXR and TSPO as new therapeutic targets to increase the levels of neuroactive steroids in the central nervous system of diabetic animals, Neurochem. Int., 60, 616, 10.1016/j.neuint.2012.02.025 Mòdol, 2012, Alteration of allopregnanolone levels affects alpha4 and delta GABAA receptor subunit expression and adult behavioural hippocampal response to neurosteroids, FENS Forum Abstr. Morali, 2012, Cytoarchitectural characteristics of hippocampal CA1 pyramidal neurons of rats, four months after global cerebral ischemia and progesterone treatment, Restor. Neurol. Neurosci., 30, 1 Noorbakhsh, 2011, Impaired neurosteroid synthesis in multiple sclerosis, Brain, 134, 2703, 10.1093/brain/awr200 Nothdurfter, 2012, Translocator protein (18kDa) as a target for novel anxiolytics with a favourable side-effect profile, J. Neuroendocrinol., 24, 82, 10.1111/j.1365-2826.2011.02166.x Nothdurfter, 2012, Recent developments in potential anxiolytic agents targeting GABAA/BzR complex or the translocator protein (18kDa) (TSPO), Curr. Top. Med. Chem., 12, 360, 10.2174/156802612799078748 Paris, 2011, Inhibition of 5 alpha-reductase activity in late pregnancy decrease gestational length and fecundity and imapairs object memory and central progestrogen milieu of juvenile rat offspring, J. Neuroendocrinol., 23, 1079, 10.1111/j.1365-2826.2011.02219.x Papadopoulos, 2009, Translocator protein (18kDa) TSPO: an emerging therapeutic target in neurotrauma, Exp. Neurol., 219, 53, 10.1016/j.expneurol.2009.04.016 Patte-Mensah, 2013, Potential role of allopregnanolone for a safe and effective therapy of neuropathic pain, Prog. Neurobiol. Pelletier, 2010, Steroidogenic enzymes in the brain: morphological aspects, Prog. Brain Res., 181, 193, 10.1016/S0079-6123(08)81011-4 Pesaresi, 2010, Sex differences in neuroactive steroid levels in the nervous system of diabetic and non-diabetic rats, Horm. Behav., 57, 46, 10.1016/j.yhbeh.2009.04.008 Pinna, 2010, In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis, Behav. Pharmacol., 21, 438, 10.1097/FBP.0b013e32833d8ba0 Roglio, 2008, Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury, Neuroscience, 155, 673, 10.1016/j.neuroscience.2008.06.034 Sayeed, 2006, Allopregnanolone, a progesterone metabolite, is more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion, Ann. Emerg. Med., 47, 381, 10.1016/j.annemergmed.2005.12.011 Sayeed, 2009, Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism for better neuroprotective effects of allopregnanolone over progesterone, Brain Res., 1263, 165, 10.1016/j.brainres.2009.01.045 Schüle, 2013, The role of allopregnanolone in depression and anxiety, Prog. Neurobiol., 111 Schumacher, 2012, Progesterone synthesis in the nervous system: implications for myelination and myelin repair, Front. Neurosci., 6, 10, 10.3389/fnins.2012.00010 Schumacher, 2003, Steroid hormones and neurosteroids in normal and pathological aging of the nervous system, Prog. Neurobiol., 71, 3, 10.1016/j.pneurobio.2003.09.004 Schumacher, 2013, Revisiting the roles of progesterone and allopregnanolone in the nervous system: resurgence of the progesterone receptors, Prog. Neurobiol., 111 Singh, 2010, Allopregnanolone, the active metabolite of progesterone protects against neuronal damage in picrotoxin-induced seizure model in mice, Pharmacol. Biochem. Behav., 94, 416, 10.1016/j.pbb.2009.10.003 Skinner, 1998, The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor, Proc. Natl. Acad. Sci. USA, 95, 10978, 10.1073/pnas.95.18.10978 Stein, 2011, Progesterone in the treatment of acute traumatic brain injury: a clinical perspective and update, Neuroscience, 191, 101, 10.1016/j.neuroscience.2011.04.013 Tsutsui, 2012, Neurosteroid biosynthesis and action during cerebellar development, Cerebellum, 11, 414, 10.1007/s12311-011-0341-7 Tsutsui, 2011, Biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell, Front. Endocrinol. (Lausanne), 2, 61, 10.3389/fendo.2011.00061 Turkmen, 2011, Tolerance to allopregnanolone with focus on the GABA-A receptor, Br. J. Pharmacol., 162, 311, 10.1111/j.1476-5381.2010.01059.x VanLandingham, 2007, Neurosteroids reduce inflammation after TBI through CD55 induction, Neurosci. Lett., 425, 94, 10.1016/j.neulet.2007.08.045 VanLandingham, 2006, The enantiomer of progesterone acts as a molecular neuroprotectant after traumatic brain injury, Neuropharmacology, 51, 1078, 10.1016/j.neuropharm.2006.07.015 Veiga, 2005, Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity, J. Neurosci. Res., 80, 129, 10.1002/jnr.20430 Wang, 2008, Regenerative potential of allopregnanolone, Brain. Res. Rev., 57, 398, 10.1016/j.brainresrev.2007.08.010 Wang, 2010, Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease, Proc. Natl. Acad. Sci. USA, 107, 6498, 10.1073/pnas.1001422107 Wang, 2002, 3Beta-hydroxypregnane steroids are pregnanolone sulfate-like GABA(A) receptor antagonists, J. Neurosci., 22, 3366, 10.1523/JNEUROSCI.22-09-03366.2002 Wirth, 2011, Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion, Front. Endocrinol. (Lausanne), 2, 19, 10.3389/fendo.2011.00019