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Allopregnanolone

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https://www.readbyqxmd.com/read/28102853/skin-to-skin-contact-after-birth-and-the-natural-course-of-neurosteroid-levels-in-healthy-term-newborns
#1
K R McCallie, N W Gaikwad, M E Castillo Cuadrado, M Aleman, J E Madigan, D K Stevenson, V K Bhutani
OBJECTIVE: To determine the postnatal course of neurosteroid levels in relation to gender, mode of delivery and the extent of skin-to-skin (STS) contact during the first days of life in healthy term newborns. STUDY DESIGN: Prospective observational study of 39 neonates in which parents recorded total duration of STS in the first 2 days and nine neurosteroids (dehydroepiandrosterone-sulfate, progesterone, pregnenolone, pregnenolone-sulfate, allopregnanolone, isopregnanolone, epipregnanolone, pregnanolone and pregnanolone-sulfate) were assayed from blood samples at birth and at 1-2 days of age...
January 19, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28102229/the-neurosteroidogenic-enzyme-5%C3%AE-reductase-mediates-psychotic-like-complications-of-sleep-deprivation
#2
Roberto Frau, Valentina Bini, Alessio Soggiu, Simona Scheggi, Alessandra Pardu, Silvia Fanni, Paola Roncada, Monica Puligheddu, Francesco Marrosu, Donatella Caruso, Paola Devoto, Marco Bortolato
Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28072455/src-and-phospho-fak-kinases-are-activated-by-allopregnanolone-promoting-schwann-cells-motility-morphology-and-myelination
#3
Simona Melfi, Maria Magdalena Montt Guevara, Veronica Bonalume, Massimiliano Ruscica, Alessandra Colciago, Tommaso Simoncini, Valerio Magnaghi
Schwann cells' (SCs) development and maturation require coordinate and complementary interaction among several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs' fate, participating in regulation of SC adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SC motility and proliferation, which are crucial processes for nerve development, maturation and regeneration...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28068457/cellular-gabaergic-neuroactive-steroid-3%C3%AE-5%C3%AE-3-hydroxy-pregnan-20-one-3%C3%AE-5%C3%AE-thp-immunostaining-levels-are-increased-in-the-ventral-tegmental-area-of-human-alcohol-use-disorder-patients-a-postmortem-study
#4
Ahmet Sait Hasirci, Antoniette M Maldonado-Devincci, Matthew C Beattie, Todd K O'Buckley, A Leslie Morrow
BACKGROUND: The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) enhances GABAergic activity and produces subjective effects similar to ethanol (EtOH). The effect of chronic alcohol exposure on 3α,5α-THP concentrations has been studied in mouse, rat, and monkey limbic brain areas. Chronic EtOH exposure produced divergent brain region and cell-specific changes in 3α,5α-THP concentrations in animal studies. However, 3α,5α-THP levels in similar human brain regions have never been examined in individuals diagnosed with alcohol use disorder (AUD)...
January 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28013353/changes-in-stress-stimulated-allopregnanolone-levels-induced-by-neonatal-estradiol-treatment-are-associated-with-enhanced-dopamine-release-in-adult-female-rats-reversal-by-progesterone-administration
#5
Patrizia Porcu, Valeria Lallai, Andrea Locci, Sandro Catzeddu, Valeria Serra, Maria Giuseppina Pisu, Mariangela Serra, Laura Dazzi, Alessandra Concas
BACKGROUND: Allopregnanolone plays a role in the stress response and homeostasis. Alterations in the estrogen milieu during the perinatal period influence brain development in a manner that persists into adulthood. Accordingly, we showed that a single administration of estradiol benzoate (EB) on the day of birth decreases brain allopregnanolone concentrations in adult female rats. OBJECTIVE: We examined whether the persistent decrease in allopregnanolone concentrations, induced by neonatal EB treatment, might affect sensitivity to stress during adulthood...
December 24, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28009705/positive-allosteric-modulation-of-gabaa-receptors-attenuates-high-blood-pressure-in-schlager-hypertensive-mice
#6
Emily R Stevenson, Esther M C Johns, Francine Z Marques, Kristy L Jackson, Pamela J Davern, Roger G Evans, Geoffrey A Head
OBJECTIVE: Blood pressure high Schlager (BPH/2J) mice have neurogenic hypertension associated with differences in hypothalamic GABAA receptors compared with their normotensive counterparts (BPN/3J). Allopregnanolone is an endogenous neurosteroid reduced in chronic stress, and when administered, decreases anxiety by positive allosteric modulation of GABAA receptors. METHODS: To determine if allopregnanolone could be a viable therapeutic for neurogenic hypertension, male BPH/2J (n = 6-7) and BPN/3J (n = 8-9) mice were equipped with radiotelemetry probes to compare cardiovascular variables before and after implantation of subcutaneous minipumps delivering allopregnanolone (5 mg/kg per day), or its vehicle, for a period of 2 weeks...
December 22, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27993636/anti-ptsd-like-effects-of-albiflorin-extracted-from-radix-paeoniae-alba
#7
Zhi-Kun Qiu, Jia-Li He, Xu Liu, Jia Zeng, Ji-Sheng Chen, Hong Nie
ETHNOPHARMACOLOGY RELEVANCE: Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder that is characterized by symptoms of re-experiencing, avoidance and hyperarousal, as well as social and professional dysfunction at least one month after the exposure to a traumatic event. Biosynthesis of allopregnanolone has been suggested as one of the important contributors to PTSD. Albiflorin (AF) extracted from Radix paeoniae Alba had been shown to be effective in the therapy of depression...
December 16, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27979708/allopregnanolone-and-its-analog-br-297-rescue-neuronal-cells-from-oxidative-stress-induced-death-through-bioenergetic-improvement
#8
Imane Lejri, Amandine Grimm, Michel Miesch, Philippe Geoffroy, Anne Eckert, Ayikoe-Guy Mensah-Nyagan
Allopregnanolone (AP) is supposed to exert beneficial actions including anxiolysis, analgesia, neurogenesis and neuroprotection. However, although mitochondrial dysfunctions are evidenced in neurodegenerative diseases, AP actions against neurodegeneration-induced mitochondrial deficits have never been investigated. Also, the therapeutic exploitation of AP is limited by its difficulty to pass the liver and its rapid clearance after sulfation or glucuronidation of its 3-hydroxyl group. Therefore, the characterization of novel potent neuroprotective analogs of AP may be of great interest...
December 13, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27913096/a-sensitive-and-accurate-lc-ms-ms-assay-with-the-derivatization-of-1-amino-4-methylpiperazine-applied-to-serum-allopregnanolone-pregnenolone-and-androsterone-in-pre-and-postmenopausal-women
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27834854/pharmacologic-treatment-assigned-for-niemann-pick-type-c1-disease-partly-changes-behavioral-traits-in-wild-type-mice
#15
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
#16
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
#17
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
#18
O Taleb, F Bouzobra, H Tekin-Pala, L Meyer, A G Mensah-Nyagan, C 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
#19
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
#20
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...
January 2017: Hormones and Behavior
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