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Neurosteroid

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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/28077388/the-na-taurocholate-cotransporting-polypeptide-ntcp-slc10a1-ortholog-in-the-marine-skate-leucoraja-erinacea-is-not-a-physiological-bile-salt-transporter
#3
Dongke Yu, Han Zhang, Daniel A Lionarons, James L Boyer, Shi-Ying Cai
The Na(+)-dependent taurocholate co-transporting polypeptide (NTCP/SLC10A1) is a hepatocyte specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of an hepatic Na(+)-dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea. The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28043845/distributions-of-therapeutically-promising-steroids-in-cellular-membranes
#4
Kamila Riedlová, Michaela Nekardová, Petr Kačer, Kamila Syslová, Mario Vazdar, Pavel Jungwirth, Eva Kudová, Lukasz Cwiklik
Interactions of two neurosteroids, inhibiting membrane-bound N-Methyl-d-aspartate receptors, with phospholipid membranes are studied. Namely, endogenous pregnanolone sulfate is compared with pregnanolone glutamate, the latter being a novel synthetic steroidal inhibitor of these receptors with potential pharmaceutical use. Molecular-level details of steroid-phospholipid membranes interactions are scrutinized employing molecular dynamics simulations supported by quantum chemical calculations to assess steroid lipophilicity...
December 30, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28038403/higher-serum-dhea-concentrations-before-and-after-ssri-treatment-are-associated-with-remission-of-major-depression
#5
Christina M Hough, Daniel Lindqvist, Elissa S Epel, Molly St Denis, Victor I Reus, F Saverio Bersani, Rebecca Rosser, Laura Mahan, Heather M Burke, Owen M Wolkowitz, Synthia H Mellon
BACKGROUND: Dehydroepiandrosterone (DHEA) and its sulfated ester DHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear...
December 5, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28028198/sex-dependent-regulation-of-aromatase-mediated-synaptic-plasticity-in-the-basolateral-amygdala
#6
Roland A Bender, Lepu Zhou, Ricardo Vierk, Nicola Brandt, Alexander Keller, Christine E Gee, Michael K E Schäfer, Gabriele M Rune
: The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17β-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM-inhibitor letrozole reduced spine synapse density in the BL of adult female mice, but not in the BL of male mice...
December 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28027915/developmental-vitamin-d-deficiency-and-autism-putative-pathogenic-mechanisms
#7
REVIEW
Asad Ali, Xiaoying Cui, Darryl Eyles
Autism is a neurodevelopmental disease that presents in early life. Despite a considerable amount of studies, the neurobiological mechanisms underlying autism remain obscure. Both genetic and environmental factors are involved in the development of autism. Vitamin D deficiency is emerging as a consistently reported risk factor in children. One reason for the prominence now being given to this risk factor is that it would appear to interact with several other epidemiological risk factors for autism. Vitamin D is an active neurosteroid and plays crucial neuroprotective roles in the developing brain...
December 24, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28027903/seasonal-changes-and-sexual-dimorphism-in-gene-expression-of-star-protein-steroidogenic-enzymes-and-sex-hormone-receptors-in-the-frog-brain
#8
Alessandra Santillo, Sara Falvo, Maria Maddalena Di Fiore, Gabriella Chieffi Baccari
The brain of amphibians contains all the key enzymes of steroidogenesis and has a high steroidogenic activity. In seasonally-breeding amphibian species brain steroid levels fluctuate synchronously with the reproductive cycle. Here we report a study of gene expression of StAR protein, key steroidogenic enzymes and sex hormone receptors in the telencephalon (T) and diencephalon-mesencephalon (D-M) of male and female reproductive and post-reproductive Pelophylax esculentus, a seasonally breeding anuran amphibian...
December 24, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28009705/positive-allosteric-modulation-of-gabaa-receptors-attenuates-high-blood-pressure-in-schlager-hypertensive-mice
#9
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/28005271/progesterone-for-acute-traumatic-brain-injury
#10
REVIEW
Junpeng Ma, Siqing Huang, Shu Qin, Chao You, Yunhui Zeng
BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain injury is of great public health importance worldwide. Progesterone is a naturally produced hormone that has well-defined pharmacokinetics, is widely available, inexpensive, and has steroidal, neuroactive and neurosteroidal actions in the central nervous system. It is, therefore, a potential candidate for treating TBI patients...
22, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27988507/epilepsy-and-vitamin-d-a-comprehensive-review-of-current-knowledge
#11
Seyed Amir Miratashi Yazdi, Mehdi Abbasi, Seyed Masoud Miratashi Yazdi
Vitamin D has been considered as neurosteroid, and its pivotal role in neuroprotection, brain development, and immunomodulation has been noticed in studies; however, our knowledge regarding its role in neurological disorders is still developing. The potential role of vitamin D in the pathophysiology and treatment of epilepsy, as one the most prevalent neurological disorders, has received less attention in recent years. In this article, we review the possible relationship between vitamin D and epilepsy from different aspects, including the action mechanism of vitamin D in the central nervous system and ecological and epidemiological findings...
December 19, 2016: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/27986860/quantification-of-ono-2952-occupancy-of-translocator-protein-18kda-in-conscious-monkey-brain-using-positron-emission-tomography
#12
Katsukuni Mitsui, Noriko Morimoto, Tomohiro Niwa, Yoshiyuki Yamaura, Hiroyuki Ohba, Hideo Tsukada, Seishi Katsumata
We have previously shown that ONO-2952, a novel translocator protein 18kDa (TSPO) antagonist, inhibits stress-induced neurosteroids accumulation and noradrenaline release in the rat brain and alleviates the subsequent symptomatic responses with a brain TSPO occupancy of 50% or more. In this study, we measured ONO-2952 brain TSPO occupancy in conscious rhesus monkeys using positron emission tomography (PET) with (11)C-PBR28 as ligand for translational research to clinical application. PET scans were performed following single and repeated oral administration of ONO-2952 at several dose levels for each animal with sequential arterial blood sampling...
December 16, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27986596/effects-of-the-synthetic-neurosteroid-ganaxolone-on-seizure-activity-and-behavioral-deficits-in-an-angelman-syndrome-mouse-model
#13
Stephanie L Ciarlone, Xinming Wang, Michael A Rogawski, Edwin J Weeber
Angelman syndrome (AS) is a rare neurogenetic disorder characterized by severe developmental delay, motor impairments, and epilepsy. GABAergic dysfunction is believed to contribute to many of the phenotypic deficits seen in AS. We hypothesized that restoration of inhibitory tone mediated by extrasynaptic GABAA receptors could provide therapeutic benefit. Here, we report that ganaxolone, a synthetic neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, was anxiolytic, anticonvulsant, and improved motor deficits in the Ube3a-deficient mouse model of AS when administered by implanted mini-pump for 3 days or 4 weeks...
December 13, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27883962/maternal-care-and-affective-behavior-in-female-offspring-implication-of-the-neurosteroid-gabaergic-system
#14
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
#15
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
#16
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/27833556/increased-motor-impairing-effects-of-the-neuroactive-steroid-pregnanolone-in-mice-with-targeted-inactivation-of-the-gabaa-receptor-%C3%AE-2-subunit-in-the-cerebellum
#17
Elli Leppä, Anni-Maija Linden, Maria I Aller, Peer Wulff, Olga Vekovischeva, Bernhard Luscher, Hartmut Lüddens, William Wisden, Esa R Korpi
Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABAA receptors. In recombinant receptors and genetic mouse models their actions depend on the α, β, and δ subunits of the receptor, especially on those that form extrasynaptic GABAA receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched γ2 subunit-containing receptors and even on αβ binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5β-pregnan-3α-ol-20-one is altered in genetically engineered mouse models that have deficient GABAA receptor-mediated synaptic inhibition in selected neuronal populations...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27802245/progesterone-treatment-shows-greater-protection-in-brain-vs-retina-in-a-rat-model%C3%A2-of-middle-cerebral-artery-occlusion-progesterone-receptor-levels-may-play-an-important-role
#18
Rachael S Allen, Iqbal Sayeed, Yuliya Oumarbaeva, Katherine C Morrison, Paul H Choi, Machelle T Pardue, Donald G Stein
BACKGROUND/OBJECTIVE: To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. METHODS: MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots...
October 13, 2016: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/27801959/different-synaptic-stimulation-patterns-influence-the-local-androgenic-and-estrogenic-neurosteroid-availability-triggering-hippocampal-synaptic-plasticity-in-the-male-rat
#19
Michela Di Mauro, Alessandro Tozzi, Paolo Calabresi, Vito Enrico Pettorossi, Silvarosa Grassi
Electrophysiological recordings were used to investigate the role of the local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on synaptic long-term effects induced in the hippocampal CA1 region of male rat slices. Long-term depression (LTD) and long-term potentiation (LTP), induced by different stimulation patterns, were examined under the block of the DHT synthesis by finasteride, and the E2 synthesis by letrozole. We used low frequency stimulation (LFS) for LTD, high frequency stimulation (HFS) for LTP, and intermediate patterns differing in duration or frequency...
November 1, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27789391/concurrent-hypothalamic-gene-expression-under-acute-and-chronic-long-days-implications-for-initiation-and-maintenance-of-photoperiodic-response-in-migratory-songbirds
#20
Ila Mishra, Sanjay K Bhardwaj, Shalie Malik, Vinod Kumar
Hypothalamic expression of the thyroid hormone (TH) responsive gonadostimulatory (eya3, cga, tshβ, dio2, dio3, gnrh, gnih) and neurosteroid pathway genes (androgen receptor [ar], aromatase [cyp19], estrogen receptor [er] α and β) was examined in photosensitive redheaded buntings exposed to 2 (acute, experiment 1) or 12 (chronic, experiment 2) long days (16L:8D). Experiment 2 also included a photorefractory group. Acute long days caused a significant increase in eya3, cga, tshβ, dio2 and gnrh and decrease in dio3 mRNA levels...
October 24, 2016: Molecular and Cellular Endocrinology
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