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https://www.readbyqxmd.com/read/27883962/maternal-care-and-affective-behavior-in-female-offspring-implication-of-the-neurosteroid-gabaergic-system
#1
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
#2
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
#3
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/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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/27777323/a-single-dose-of-allopregnanolone-affects-the-ovarian-morphology-and-steroidogenesis
#8
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
#9
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/27753644/tryptophan-and-cysteine-mutations-in-m1-helices-of-%C3%AE-1%C3%AE-3%C3%AE-2l-%C3%AE-aminobutyric-acid-type-a-receptors-indicate-distinct-intersubunit-sites-for-four-intravenous-anesthetics-and-one-orphan-site
#10
Anahita Nourmahnad, Alex T Stern, Mayo Hotta, Deirdre S Stewart, Alexis M Ziemba, Andrea Szabo, Stuart A Forman
BACKGROUND: γ-Aminobutyric acid type A (GABAA) receptors mediate important effects of intravenous general anesthetics. Photolabel derivatives of etomidate, propofol, barbiturates, and a neurosteroid get incorporated in GABAA receptor transmembrane helices M1 and M3 adjacent to intersubunit pockets. However, photolabels have not been consistently targeted at heteromeric αβγ receptors and do not form adducts with all contact residues. Complementary approaches may further define anesthetic sites in typical GABAA receptors...
December 2016: Anesthesiology
https://www.readbyqxmd.com/read/27735054/2-deoxy-d-glucose-enhances-tonic-inhibition-through-the-neurosteroid-mediated-activation-of-extrasynaptic-gabaa-receptors
#11
Nicola Forte, Lucian Medrihan, Beatrice Cappetti, Pietro Baldelli, Fabio Benfenati
OBJECTIVE: The inhibition of glycolysis exerts potent antiseizure effects, as demonstrated by the efficacy of ketogenic and low-glucose/nonketogenic diets in the treatment of drug-resistant epilepsy. ATP-sensitive potassium (KATP ) channels have been initially identified as the main determinant of the reduction of neuronal hyperexcitability. However, a plethora of other mechanisms have been proposed. Herein, we report the ability of 2-deoxy-d-glucose (2-DG), a glucose analog that inhibits glycolytic enzymes, of potentiating γ-aminobutyric acid (GABA)ergic tonic inhibition via neurosteroid-mediated activation of extrasynaptic GABAA receptors...
October 13, 2016: Epilepsia
https://www.readbyqxmd.com/read/27717041/effects-of-gabra2-point-mutations-on-alcohol-intake-increased-binge-like-and-blunted-chronic-drinking-by-mice
#12
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/27716798/microneurotrophins-improve-survival-in-motor-neuron-astrocyte-co-cultures-but-do-not-improve-disease-phenotypes-in-a-mutant-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#13
Kelly E Glajch, Laura Ferraiuolo, Kaly A Mueller, Matthew J Stopford, Varsha Prabhkar, Achille Gravanis, Pamela J Shaw, Ghazaleh Sadri-Vakili
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease caused by loss of motor neurons. ALS patients experience rapid deterioration in muscle function with an average lifespan of 3-5 years after diagnosis. Currently, the most effective therapeutic only extends lifespan by a few months, thus highlighting the need for new and improved therapies. Neurotrophic factors (NTFs) are important for neuronal development, maintenance, and survival. NTF treatment has previously shown efficacy in pre-clinical ALS models...
2016: PloS One
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
#14
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/27650467/could-gonadal-and-adrenal-androgen-deficiencies-contribute-to-the-depressive-symptoms-in-men-with-systolic-heart-failure
#15
Katarzyna Kulej-Lyko, Jacek Majda, Stephan von Haehling, Wolfram Doehner, Monika Lopuszanska, Alicja Szklarska, Waldemar Banasiak, Stefan D Anker, Piotr Ponikowski, Ewa A Jankowska
BACKGROUND: Testosterone (TT) and dehydroepiandrosterone sulphate (DHEAS) are neurosteroids and their deficiencies constitute the hormone risk factors promoting the development of depression in elderly otherwise healthy men. We investigated the link between hypogonadism and depression in accordance with age and concomitant diseases in men with systolic HF using the novel scale previously dedicated for elderly population. METHODS: We analysed the prevalence of depression and severity of depressive symptoms in population of 226 men with systolic HF (40-80 years) compared to 379 healthy peers...
September 20, 2016: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/27632921/dietary-withdrawal-of-phytoestrogens-resulted-in-higher-gene-expression-of-3-beta-hsd-and-aro-but-lower-5-alpha-r-1-in-male-rats
#16
María F Andreoli, Cora Stoker, María F Rossetti, Gisela P Lazzarino, Enrique H Luque, Jorge G Ramos
Removing dietary phytoestrogens causes obesity and diabetes in adult male rats. Based on the facts that hypothalamic food intake control is disrupted in phytoestrogen-deprived animals and that several steroids affect food intake, we hypothesized that phytoestrogen withdrawal alters the expression of hypothalamic steroidogenic enzymes. Male Wistar rats fed with a high-phytoestrogen diet from conception to adulthood were subjected to phytoestrogen withdrawal by feeding them a low-phytoestrogen diet or a high-phytoestrogen, high-fat diet...
September 2016: Nutrition Research
https://www.readbyqxmd.com/read/27616978/brain-and-serum-androsterone-is-elevated-in-response-to-stress-in-rats-with-mild-traumatic-brain-injury
#17
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/27599516/dependence-of-anxiolytic-effects-of-the-dipeptide-tspo-ligand-gd-23-on-neurosteroid-biosynthesis
#18
T A Gudasheva, O A Deeva, M A Yarkova, S B Seredenin
The elevated plus maze test showed that GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide), an original dipeptide ligand of TSPO, exerted anxiolytic effect when injected intraperitoneally at a dose of 0.5 mg/kg. This effect was completely blocked by the selective neurosteroid synthesis inhibitors, enzymes trilostane and finasteride. The same inhibitors do not prevent the anxiolytic effects of the benzodiazepine tranquillizer diazepam. The results of the study indicate the selective neurosteroidogenic mechanism of the anxiolytic action of GD-23...
July 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27597394/progesterone-treatment-modulates-mrna-of-neurosteroidogenic-enzymes-in-a-murine-model-of-multiple-sclerosis
#19
Laura Garay, Paula Gonzalez Giqueaux, Rachida Guennoun, Michael Schumacher, Maria Claudia Gonzalez Deniselle, Alejandro F De Nicola
Previous studies of experimental autoimmune encephalomyelitis (EAE) have shown that progesterone decreases inflammatory cell infiltration and proinflammatory factors, increases myelination and attenuates clinical grade of EAE mice. To elucidate potential mediators of these effects, we analyzed the mRNA expression of neurosteroidogenic enzymes in the spinal cord, in view of the protective role of steroids in EAE. We also analyzed mitochondrial morphology and dynamics (fusion and fission proteins), considering the role of mitochondria in neurosteroidogenesis...
September 2, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27596950/tspo-activation-modulates-the-effects-of-high-pressure-in-a-rat-ex%C3%A2-vivo-glaucoma-model
#20
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
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