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pregnenolone, learning

L Rajagopal, D Soni, H Y Meltzer
BACKGROUND: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA ) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A  R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients...
May 23, 2018: Behavioural Brain Research
M Zeeshan Qaiser, Diana E M Dolman, David J Begley, N Joan Abbott, Mihaela Cazacu-Davidescu, Delia I Corol, Jonathan P Fry
Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found (3) H-PregS to enter more rapidly than (3) H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes...
September 2017: Journal of Neurochemistry
Weisheng Wang, Yousheng Jia, Danielle T Pham, Linda C Palmer, Kwang-Mook Jung, Conor D Cox, Gavin Rumbaugh, Daniele Piomelli, Christine M Gall, Gary Lynch
Endocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus. The first is pregnenolone sensitive, targets vesicular protein Munc18-1 and depresses transmitter release; this cascade is engaged by CB1Rs in Schaffer-Commissural afferents to CA1 but not in the LPP, and it does not contribute to LTP...
May 17, 2017: Cerebral Cortex
Laila Abdel-Hafiz, Owen Y Chao, Joseph P Huston, Susanne Nikolaus, Richard E Spieler, Maria A de Souza Silva, Claudia Mattern
The neurosteroid pregnenolone (PREG) has been shown to have memory-enhancing and anti-depressant action. The present study addresses the question of whether intranasally applied pregnenolone (IN-PREG) also has promnestic properties in the rat. We examined the effects of IN-PREG at doses of 0.187 and 0.373mg/kg on memory for objects and their location on learning and retention of escape in a water maze, and on behavior on the elevated plus maze. The main findings were: (a) Pre-trial, but not post-trial, administration of IN-PREG facilitated long-term memory in a novel object-preference test and a novel object-location preference test when tested 48h after dosing...
September 2016: Neurobiology of Learning and Memory
M F Rossetti, M J Cambiasso, M A Holschbach, R Cabrera
When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions...
July 2016: Journal of Neuroendocrinology
Jui-Hsia Weng, Bon-Chu Chung
Steroids have been widely used in the clinical setting. They bind and activate nuclear receptors to regulate gene expression. In addition to activating genomic transcription, steroids also exert nongenomic actions. The current article focuses on the nongenomic actions of neurosteroids, including pregnenolone (P5), 7α-hydroxypregnenolone, pregnenolone sulfate and allopregnanolone. Pregnenolone and its derivatives promote neuronal activity by enhancing learning and memory, relieving depression, enhancing locomotor activity, and promoting neuronal cell survival...
July 2016: Steroids
M Kellner, S Nowack, V Wortmann, A Yassouridis, K Wiedemann
Exposure therapy is an effective cognitive-behavioral treatment for patients with obsessive-compulsive disorder (OCD). However, a further amelioration of symptoms by additional drugs that enhance extinction learning is desirable. An interesting candidate is pregnenolone, which positively modulates NMDA and GABAA receptors in preclinical studies and influences amygdala and prefrontal activity in humans. We present pilot data showing high acceptance and good tolerability of pregnenolone given 2 h before exposure sessions in OCD patients...
March 2016: Pharmacopsychiatry
M Dastgheib, A R Dehpour, M Heidari, L Moezi
Learning and memory impairment is one of the most challenging complications of cirrhosis and present treatments are unsatisfactory. The exact mechanism of cirrhosis cognitive dysfunction is unknown. Pregnenolone sulfate (PREGS) is an excitatory neurosteroid that acts as a N-methyl-D-aspartate (NMDA) receptor agonist and GABAA receptor antagonist. In this study we evaluated the effect of intra CA1 infusion of PREGS on cirrhotic rats' memory function using the Y-maze test. Hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression was also evaluated...
October 15, 2015: Neuroscience
P Wong, Y Sze, C C R Chang, J Lee, X Zhang
Pregnenolone sulfate, an endogenous neurosteroid in the central nervous system, is a positive allosteric modulator of the NMDA receptor, and plays a role in the modulation of learning and memory. Here, we study the actions of pregnenolone sulfate using the dopamine transporter knockout (DAT-KO) mice, which exhibit endophenotypes that recapitulate certain symptoms of schizophrenia, including the psychomotor agitation, stereotypy, prepulse inhibition (PPI) deficits and cognitive impairments. We found that acute treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of DAT-KO mice...
March 17, 2015: Translational Psychiatry
Sha Liu, Honghai Wu, Gai Xue, Xin Ma, Jie Wu, Yabin Qin, Yanning Hou
A correlation between metabolic alterations of neuroactive steroids and Alzheimer's disease remains unknown. In the present study, amyloid beta (Aβ) 25-35 (Aβ25-35) injected into the bilateral hippocampus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was significantly elevated...
October 25, 2013: Neural Regeneration Research
Conor C Smith, Stella C Martin, Kavitha Sugunan, Shelley J Russek, Terrell T Gibbs, David H Farb
Fast excitatory synaptic transmission that is contingent upon N-methyl d-aspartate receptor (NMDAR) function contributes to core information flow in the central nervous system and to the plasticity of neural circuits that underlie cognition. Hypoactivity of excitatory NMDAR-mediated neurotransmission is hypothesized to underlie the pathophysiology of schizophrenia, including the associated cognitive deficits. The neurosteroid pregnenolone (PREG) and its metabolites pregnenolone sulfate (PregS) and allopregnanolone in serum are inversely associated with cognitive improvements after oral PREG therapy, raising the possibility that brain neurosteroid levels may be modulated therapeutically...
October 2014: Molecular Pharmacology
Christine E Marx, Jimmy Lee, Mythily Subramaniam, Attilio Rapisarda, Dianne C T Bautista, Edwin Chan, Jason D Kilts, Robert W Buchanan, Eu Pui Wai, Swapna Verma, Kang Sim, Jayaraman Hariram, Rajesh Jacob, Richard S E Keefe, Siow Ann Chong
RATIONALE: Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids...
September 2014: Psychopharmacology
Conor C Smith, Terrell T Gibbs, David H Farb
RATIONALE: The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years. OBJECTIVES: New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update...
September 2014: Psychopharmacology
Fadia El Bitar, Johann Meunier, Vanessa Villard, Marion Alméras, Kathiresan Krishnan, Douglas F Covey, Tangui Maurice, Yvette Akwa
RATIONALE: Pregnenolone sulfate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are pro-amnesic, anti-amnesic and neuroprotective steroids in rodents. In Alzheimer's disease (AD) patient's brains, their low concentrations are correlated with high levels of Aβ and tau proteins. The unnatural enantiomer ent-PREGS enhanced memory in rodents. We investigated here whether ent-PREGS and ent-DHEAS could be neuroprotective in AD models. OBJECTIVE: The effects of PREGS, ent-PREGS, DHEAS and ent-DHEAS against Aβ25-35 peptide-induced toxicity were examined in vitro on B104 neuroblastoma cells and in vivo in mice...
September 2014: Psychopharmacology
Alba Gonzalez-Usano, Omar Cauli, Ana Agusti, Vicente Felipo
Around 40% of cirrhotic patients show minimal hepatic encephalopathy (MHE), with mild cognitive impairment which reduces their quality of life and life span. Treatment of MHE is unsatisfactory, and there are no specific treatments for the neurological alterations in MHE. Hyperammonemia is the main contributor to neurological alterations in MHE. New agents acting on molecular targets involved in brain mechanisms leading to neurological alterations are needed to treat MHE. Chronic hyperammonemia impairs learning of a Y-maze task by impairing the glutamate-nitric-oxide (NO)-cGMP pathway in cerebellum, in part by enhancing GABA(A) receptor activation, which also induces motor in-coordination...
February 19, 2014: ACS Chemical Neuroscience
Fulvio Plescia, Pierangelo Sardo, Valerio Rizzo, Silvana Cacace, Rosa Anna Maria Marino, Anna Brancato, Giuseppe Ferraro, Fabio Carletti, Carla Cannizzaro
Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation-acquisition and object discrimination in a simple and in a complex version of the visual task...
January 1, 2014: Behavioural Brain Research
Fulvio Plescia, Rosa A M Marino, Emanuele Cannizzaro, Anna Brancato, Carla Cannizzaro
Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study...
October 2013: Behavioural Processes
Jimei Bu, Hengbing Zu
OBJECTIVE: To observe the effect of pregnenolone (PREG) intervention on the cholinergic system function and the synaptic protein 1 (SYP1) expression in different brain regions of aged rats. METHOD: Twenty-four-month-old male Sprague Dawley rats intraperitoneally injected every other day for one month were divided into blank control group, solvent control group, PREG (0.5 mg/kg) intervention group and PREG (2.0 mg/kg) intervention group. The rats were sacrificed 2 d after the intervention and the corresponding regions of brain tissue were separated and cryopreserved...
February 2014: International Journal of Neuroscience
Emmanuel Kostakis, Conor Smith, Ming-Kuei Jang, Stella C Martin, Kyle G Richards, Shelley J Russek, Terrell T Gibbs, David H Farb
N-methyl D-aspartate (NMDA) receptors (NMDARs) mediate fast excitatory synaptic transmission and play a critical role in synaptic plasticity associated with learning and memory. NMDAR hypoactivity has been implicated in the pathophysiology of schizophrenia, and clinical studies have revealed reduced negative symptoms of schizophrenia with a dose of pregnenolone that elevates serum levels of the neuroactive steroid pregnenolone sulfate (PregS). This report describes a novel process of delayed-onset potentiation whereby PregS approximately doubles the cell's response to NMDA via a mechanism that is pharmacologically and kinetically distinct from rapid positive allosteric modulation by PregS...
August 2013: Molecular Pharmacology
Christa M Helms, Aubrey D McCracken, Sharon L Heichman, Travis M Moschak
Past studies have suggested that progesterone-derived ovarian hormones contribute to the discriminative stimulus effects of ethanol, particularly via progesterone metabolites that act at γ-aminobutyric acid type A (GABA(A)) receptors. It is unknown whether loss of ovarian hormones in women, for example, after menopause, may be associated with altered receptor mediation of the effects of ethanol. The current study measured the substitution of allopregnanolone, pregnanolone, pentobarbital, midazolam, dizocilpine, TFMPP, and RU 24969 in female sham and ovariectomized rats trained to discriminate 1...
April 2013: Behavioural Pharmacology
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