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Allopregnanolone

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https://www.readbyqxmd.com/read/27913096/a-sensitive-and-accurate-lc-ms-ms-assay-with-the-derivatization-of-1amino4methylpiperazine-applied-to-serum-allopregnanolone-pregnenolone-and-androsterone-in-pre-and-postmenopausal-women
#1
Yuyong Ke, Renaud Gonthier, Fernand Labrie
The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challenge for their accurate measurements in serum or plasma. In this report, a sensitive and reliable LC-MS/MS assay method has been developed using a simple sample preparation and the 1-Amino-4-methylpiperazine (AMP) derivatization procedure. A 5pg/ml (0.1pg on column) of low limit of quantitation has been achieved for Allopreg, Preg and ADT, with a sensitivity comparable to data obtained with the commercial reagent...
November 29, 2016: Steroids
https://www.readbyqxmd.com/read/27888513/decreased-allopregnanolone-levels-in-cerebrospinal-fluid-obtained-during-status-epilepticus
#2
Stefano Meletti, Chiara Lucchi, Giulia Monti, Giada Giovannini, Roberta Bedin, Tommaso Trenti, Cecilia Rustichelli, Giuseppe Biagini
Neuroactive steroids are increasingly considered as relevant modulators of neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS) have been shown to possess, respectively, anticonvulsant or proconvulsant properties. In view of the potential role of these steroids, we aimed at evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples obtained from patients with status epilepticus (SE). To this purpose, we enrolled 41 patients affected by SE and 41 subjects investigated for nonepileptic neurologic disorders...
November 26, 2016: Epilepsia
https://www.readbyqxmd.com/read/27886206/the-antidepressant-like-activity-of-ac-5216-a-ligand-for-18kda-translocator-protein-tspo-in-an-animal-model-of-diabetes-mellitus
#3
Zhi-Kun Qiu, Jia-Li He, Xu Liu, Guan-Hua Zhang, Jia Zeng, Hong Nie, Yong-Gang Shen, Ji-Sheng Chen
Diabetes mellitus is a chronic disease that is associated with depression. Also, depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator protein (18kDa) (TSPO) and allopregnanolone play an important role in the depression treatment. However, few studies have evaluated TSPO and allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The present study aimed to explore antidepressant-like effects of AC-5216 on diabetic rats...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27883962/maternal-care-and-affective-behavior-in-female-offspring-implication-of-the-neurosteroid-gabaergic-system
#4
Amanda P Borrow, Nicole M Cameron
In female rats, the proestrus phase of the estrous cycle is associated with decreased levels of anxiety-like and depressive-like behavior relative to the metestrus phase. Progesterone likely modulate these behaviors, in part through the influence of its metabolite, allopregnanolone (THP) on hippocampal GABAAR subunit expression. As natural variations in maternal care have been found to influence both progesterone levels at proestrus and anxiety-like behavior in female offspring, we sought to investigate the importance of maternal care and the estrous cycle on affective behavior in female rats that had received Low or High levels of licking/grooming (LG) during early life...
November 5, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27870400/sex-differences-in-the-anticonvulsant-activity-of-neurosteroids
#5
REVIEW
Doodipala Samba Reddy
Epilepsy is one of the leading causes of chronic neurological morbidity worldwide. Acquired epilepsy may result from a number of conditions, such as brain injury, anoxia, tumors, stroke, neurotoxicity, and prolonged seizures. Sex differences have been observed in many seizure types; however, some sex-specific seizure disorders are much more prevalent in women. Despite some inconsistencies, substantial data indicates that sensitivity to seizure stimuli differs between the sexes. Men generally exhibit greater seizure susceptibility than women, whereas many women with epilepsy experience a cyclical occurrence of seizures that tends to center around the menstrual period, which has been termed catamenial epilepsy...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27845056/antidepressant-like-effects-of-yl-ipa08-a-potent-ligand-for-the-translocator-protein-18%C3%A2-kda-in-chronically-stressed-rats
#6
Li-Ming Zhang, Yu-Lu Wang, Yan-Qin Liu, Rui Xue, You-Zhi Zhang, Ri-Fang Yang, Yun-Feng Li
The present study aimed to examine the molecular and cellular mechanisms underlying the antidepressant-like effect of YL-IPA08, a novel TSPO ligand designed and synthesized at our institute. We firstly used the chronic unpredictable stress (CUS) procedure of rats, a well validated stress-related animal model of depression, to further determine the antidepressant-like of YL-IPA08. And we found that YL-IPA08 caused significant suppression of inhibiting of locomotor activity, reducing the sucrose preference and increasing the latency to eat induced by CUS...
November 11, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27834854/pharmacologic-treatment-assigned-for-niemann-pick-type-c1-disease-partly-changes-behavioral-traits-in-wild-type-mice
#7
Victoria Schlegel, Markus Thieme, Carsten Holzmann, Martin Witt, Ulrike Grittner, Arndt Rolfs, Andreas Wree
Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1(nih)Npc1(-/-) mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1(-/-) animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27824503/nestorone%C3%A2-nes-a-novel-progestin-for-non-oral-contraception-structure-activity-relationships-and-brain-metabolism-studies
#8
Narender Kumar, Jerôme Fagart, Philippe Liere, Scott J Mitchell, Alanah R Knibb, Isabelle Petit-Topin, Marion Rame, Martine El-Etr, Michael Schumacher, Jeremy J Lambert, Marie-Edith Rafestin-Oblin, Regine Sitruk-Ware
Nestorone® (NES) is a highly potent non-androgenic progestin being developed for contraception. NES is a synthetic progestin that may possess neuroprotective and myelin regenerative potential as an added health benefits. In receptor transactivation experiments, NES displayed greater potency than progesterone to transactivate the human progesterone receptor (hPR). This was confirmed by docking experiments which revealed that NES adopts the same docking position within the PR ligand-binding domain (LBD) as progesterone and forms additional stabilizing contacts between 17α-acetoxy and 16-methylene groups and PR LBD supporting its higher potency than progesterone...
November 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27803668/lentiviral-mediated-overexpression-of-the-18-kda-translocator-protein-tspo-in-the-hippocampal-dentate-gyrus-ameliorates-lps-induced-cognitive-impairment-in-mice
#9
Wei Wang, Liming Zhang, Xiaoying Zhang, Rui Xue, Lei Li, Weixing Zhao, Qiang Fu, Weidong Mi, Yunfeng Li
The 18 kDa translocator protein (TSPO) is involved in the immune/inflammatory response. However, the exact role that TSPO plays in neuroinflammation-induced cognitive impairment is still elusive. The purpose of our present study was to investigate the effects of lentiviral-mediated hippocampal overexpression of the TSPO in a mouse model of LPS-induced cognitive impairment. We established a mouse cognitive impairment model using systematic daily administration of lipopolysaccharide (LPS) (0.5 mg/kg). Microinjection of the dentate gyrus of the mouse with lentiviral vectors, which contained a cDNA targeting TSPO (Lv-TSPO), resulted in a significant increase in TSPO expression and allopregnanolone production...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27789344/behavioral-and-electromyographic-assessment-of-oxaliplatin-induced-motor-dysfunctions-evidence-for-a-therapeutic-effect-of-allopregnanolone
#10
Omar Taleb, Fateh Bouzobra, Hava Tekin-Pala, Laurence Meyer, Ayikoé, G Mensah-Nyagan, Christine Patte-Mensah
The antineoplastic oxaliplatin (OXAL) is pivotal for metastatic cancer treatments. However, OXAL evokes sensory and motor side-effects including pain, muscle weakness, motor nerve fiber dysfunctions/neuropathies that significantly impact patients' lives. Therefore, preclinical investigations are struggling to characterize effective analgesics against OXAL-induced painful/sensory symptoms but surprisingly, OXAL-evoked motor dysfunctions received little attention although these neurological symptoms are also disabling for patients...
October 24, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27777323/a-single-dose-of-allopregnanolone-affects-the-ovarian-morphology-and-steroidogenesis
#11
Laura T Pelegrina, Antonella Rr Cáceres, Fernando A Giuliani, Joana A Asensio, Fernanda Parborell, Myriam Raquel Laconi
Allopregnanolone, a progesterone metabolite, is one of the best characterized neurosteroids. In a dose that mimics serum levels during stress, allopregnanolone inhibits sexual receptivity and ovulation and induces a decrease in luteinizing hormone levels. The aim of this work was to examine the effect of an intracerebroventricular administration of allopregnanolone on ovarian morphophysiology, serum and tissue levels of progesterone and estrogen, and enzymatic activity of 3β-hydroxysteroid dehydrogenase, 20α-hydroxysteroid dehydrogenase and 3α-hydroxysteroid oxido-reductase in the ovary and in the medial basal hypothalamus on the morning of estrus...
October 24, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27769760/neonatal-estradiol-exposure-to-female-rats-changes-gabaa-receptor-expression-and-function-and-spatial-learning-during-adulthood
#12
Andrea Locci, Patrizia Porcu, Giuseppe Talani, Francesca Santoru, Roberta Berretti, Elisa Giunti, Valentina Licheri, Enrico Sanna, Alessandra Concas
Exposure of female rats to estradiol during the perinatal period has profound effects on GABAergic neurotransmission that are crucial to establish sexually dimorphic brain characteristics. We previously showed that neonatal β-estradiol 3-benzoate (EB) treatment decreases brain concentrations of the neurosteroid allopregnanolone, a potent positive modulator of extrasynaptic GABAA receptors (GABAAR). We thus evaluated whether neonatal EB treatment affects GABAAR expression and function in the hippocampus of adult female rats...
October 18, 2016: Hormones and Behavior
https://www.readbyqxmd.com/read/27743930/endogenous-and-synthetic-neuroactive-steroids-evoke-sustained-increases-in-the-efficacy-of-gabaergic-inhibition-via-a-protein-kinase%C3%A2-c-dependent-mechanism
#13
Amit Modgil, Manasa L Parakala, Michael A Ackley, James J Doherty, Stephen J Moss, Paul A Davies
The neuroactive steroid (NAS) tetrahydrodeoxycorticosterone (THDOC) increases protein kinase C (PKC) mediated phosphorylation of extrasynaptic GABAA receptor (GABAAR) subunits leading to increased surface expression of α4/β3 subunit-containing extrasynaptic GABAARs, leading to a sustained increase in GABAAR tonic current density. Whether other naturally occurring and synthetic NASs share both an allosteric and metabotropic action on GABAARs is unknown. Here, we examine the allosteric and metabotropic properties of allopregnanolone (ALLO), and synthetic NASs SGE-516 and ganaxolone...
October 12, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27717041/effects-of-gabra2-point-mutations-on-alcohol-intake-increased-binge-like-and-blunted-chronic-drinking-by-mice
#14
Emily L Newman, Georgia Gunner, Polly Huynh, Darrel Gachette, Stephen J Moss, Trevor G Smart, Uwe Rudolph, Joseph F DeBold, Klaus A Miczek
BACKGROUND: Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans. Deficient GABAergic functioning is linked to impulse control disorders, intermittent explosive disorder, and to drug abuse and dependence, yet it remains unclear whether α2-containing GABAA receptor sensitivity to endogenous ligands is involved in excessive alcohol drinking. METHODS: Male wild-type (Wt) C57BL/6J and point-mutated mice rendered insensitive to GABAergic modulation by benzodiazepines (BZD; H101R), allopregnanolone (ALLO) or tetrahydrodeoxycorticosterone (THDOC; Q241M), or high concentrations of ethanol (EtOH) (S270H/L277A) at α2-containing GABAA receptors were assessed for their binge-like, moderate, or escalated chronic drinking using drinking in the dark, continuous access (CA) and intermittent access (IA) to alcohol protocols, respectively...
November 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27662401/neurosteroid-allopregnanolone-suppresses-median-nerve-injury-induced-mechanical-hypersensitivity-and-glial-extracellular-signal-regulated-kinase-activation-through-%C3%AE-aminobutyric-acid-type-a-receptor-modulation-in-the-rat-cuneate-nucleus
#15
Chun-Ta Huang, Seu-Hwa Chen, June-Horng Lue, Chi-Fen Chang, Wen-Hsin Wen, Yi-Ju Tsai
BACKGROUND: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. METHODS: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development...
September 23, 2016: Anesthesiology
https://www.readbyqxmd.com/read/27616978/brain-and-serum-androsterone-is-elevated-in-response-to-stress-in-rats-with-mild-traumatic-brain-injury
#16
Richard J Servatius, Christine E Marx, Swamini Sinha, Pelin Avcu, Jason D Kilts, Jennifer C Naylor, Kevin C H Pang
Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON)...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27596950/tspo-activation-modulates-the-effects-of-high-pressure-in-a-rat-ex%C3%A2-vivo-glaucoma-model
#17
Makoto Ishikawa, Takeshi Yoshitomi, Douglas F Covey, Charles F Zorumski, Yukitoshi Izumi
We previously reported that elevated pressure induces axonal swelling and facilitates the synthesis of the neurosteroid, allopregnanolone (AlloP), in the ex vivo rat retina. Exogenously applied AlloP attenuates the axonal swelling, suggesting that the neurosteroid plays a neuroprotective role against glaucomatous pressure-induced injuries, although mechanisms underlying neurosteroidogenesis have not been clarified. The aim of this study was to determine whether AlloP synthesis involves activation of translocator protein 18 kD (TSPO) and whether TSPO modulates pressure-induced retinal injury...
December 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27571131/steroid-profiling-in-male-wobbler-mouse-a-model-of-amyotrophic-lateral-sclerosis
#18
Maria Claudia Gonzalez Deniselle, Philippe Liere, Antoine Pianos, Maria Meyer, Fanny Aprahamian, Annie Cambourg, Noelia P Di Giorgio, Michael Schumacher, Alejandro F De Nicola, Rachida Guennoun
The The Wobbler mouse is an animal model for human motoneuron diseases, especially amyotrophic lateral sclerosis (ALS), used in the investigation of both pathology and therapeutic treatment. ALS is a fatal neurodegenerative disease, characterized by the selective and progressive death of motoneurons, leading to progressive paralysis. Previous limited studies have reported steroidal hormone dysregulation in Wobbler mouse and in ALS patients, suggesting endocrine dysfunctions which may be involved in the pathogenesis of the disease...
August 29, 2016: Endocrinology
https://www.readbyqxmd.com/read/27568209/progestin-withdrawal-at-parturition-in-the-mare
#19
Erin L Legacki, C J Corbin, B A Ball, M Wynn, S Loux, S D Stanley, A J Conley
Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3β, 20α-diol (3β,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry...
October 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27529315/synergistic-modulation-of-%C3%AE-aminobutyric-acid-type-a-receptor-mediated-synaptic-inhibition-in-cortical-networks-by-allopregnanolone-and-propofol
#20
Berthold Drexler, Monika Balk, Bernd Antkowiak
BACKGROUND: The neuroactive steroid allopregnanolone (ALLO) is an endogenous allosteric modulator of γ-aminobutyric acid type A (GABAA) receptors. There is evidence that ALLO, at physiologically relevant concentrations, modulates GABAA receptor function in the cerebral cortex. The widely used anesthetic agent propofol and ALLO share a similar mode of molecular action. Here, we ask how GABAA receptor-mediated synaptic inhibition and action potential firing of neurons in cultured cortical slices are altered by either ALLO or propofol or by coapplying both agents...
October 2016: Anesthesia and Analgesia
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