The Experts below are selected from a list of 1935 Experts worldwide ranked by ideXlab platform

Willy Mayo - One of the best experts on this subject based on the ideXlab platform.

  • Pregnenolone Sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.
    Neurobiology of Aging, 2005
    Co-Authors: Willy Mayo, Michel Le Moal, Valérie Lemaire, Jordane Malaterre, José J. Rodríguez, Myriam Cayre, Michael G. Stewart, Martine Kharouby, Geneviève Rougon, Pier Vincenzo Piazza
    Abstract:

    Abstract Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid Pregnenolone-Sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABAA) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances.

  • Sleep-wake states and cortical synchronization control by Pregnenolone Sulfate into the pedunculopontine nucleus.
    Journal of Neuroscience Research, 2004
    Co-Authors: Sònia Darbra, Michel Le Moal, Pier Vincenzo Piazza, Olivier George, Jean-jacques Bouyer, Willy Mayo
    Abstract:

    Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are crucial for initiation and maintenance of electroencephalographic (EEG) desynchronization states like paradoxical sleep and wakefulness. These neurons are regulated by classical neurotransmitter systems from the pontomesencephalic reticular formation and basal ganglia. In addition to this regulation, PPT neuron activity could be modulated by endogenous neurosteroids and particularly by Pregnenolone Sulfate (PREG-S) because synthesis enzymes of this neurosteroid are present in this area and peripheral administrations of PREG-S affect sleep-wakefulness states. To test this hypothesis, we studied the effects of different doses of PREG-S infusion into the PPT on sleep-wakefulness states in rats. Our results show dose-dependent effects of PREG-S on sleep-wakefulness states. Low concentration of PREG-S (5 ng) increased the amount of paradoxical sleep without any modification of slow wave sleep and wakefulness. High level of PREG-S (10 and 20 ng) increased paradoxical sleep and slow wave sleep together with an increase of delta power and a decrease of theta power during wakefulness. Dependent on the doses used, PREG-S thus can promote paradoxical sleep alone or the global propensity to fall asleep, impairing the quality of wakefulness. These results unveil a new regulation pathway for PPT neurons and strengthen the role of PREG-S in sleep-wakefulness regulation.

  • Individual differences in cognitive aging: implication of Pregnenolone Sulfate.
    Progress in Neurobiology, 2003
    Co-Authors: Willy Mayo, Marc Pallarès, Muriel Darnaudéry, Michel Le Moal, Jean Bouyer, Olivier George, Sònia Darbra, Monique Vallée, Valérie Lemaire-mayo, Pier Vincenzo Piazza
    Abstract:

    In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the Pregnenolone Sulfate (PREG-S). Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging and severely altered in human neurodegenerative pathologies like Alzheimer’s disease. In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep–wakefulness cycle, and particularly the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young animals. Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer’s disease, have also been related to alterations of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator properties of this steroid at the GABAA receptor level. Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.

  • The Neurosteroid Pregnenolone Sulfate Increases Cortical Acetylcholine Release: A Microdialysis Study in Freely Moving Rats
    Journal of Neurochemistry, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Muriel Koehl, Willy Mayo
    Abstract:

    The effects of Pregnenolone Sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.

  • The neurosteroid Pregnenolone Sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.
    Brain Research, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Pier Vincenzo Piazza, Willy Mayo
    Abstract:

    The effects of an infusion of the neurosteroid Pregnenolone Sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that Pregnenolone Sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.

Michel Le Moal - One of the best experts on this subject based on the ideXlab platform.

  • Pregnenolone Sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.
    Neurobiology of Aging, 2005
    Co-Authors: Willy Mayo, Michel Le Moal, Valérie Lemaire, Jordane Malaterre, José J. Rodríguez, Myriam Cayre, Michael G. Stewart, Martine Kharouby, Geneviève Rougon, Pier Vincenzo Piazza
    Abstract:

    Abstract Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid Pregnenolone-Sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABAA) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances.

  • Sleep-wake states and cortical synchronization control by Pregnenolone Sulfate into the pedunculopontine nucleus.
    Journal of Neuroscience Research, 2004
    Co-Authors: Sònia Darbra, Michel Le Moal, Pier Vincenzo Piazza, Olivier George, Jean-jacques Bouyer, Willy Mayo
    Abstract:

    Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are crucial for initiation and maintenance of electroencephalographic (EEG) desynchronization states like paradoxical sleep and wakefulness. These neurons are regulated by classical neurotransmitter systems from the pontomesencephalic reticular formation and basal ganglia. In addition to this regulation, PPT neuron activity could be modulated by endogenous neurosteroids and particularly by Pregnenolone Sulfate (PREG-S) because synthesis enzymes of this neurosteroid are present in this area and peripheral administrations of PREG-S affect sleep-wakefulness states. To test this hypothesis, we studied the effects of different doses of PREG-S infusion into the PPT on sleep-wakefulness states in rats. Our results show dose-dependent effects of PREG-S on sleep-wakefulness states. Low concentration of PREG-S (5 ng) increased the amount of paradoxical sleep without any modification of slow wave sleep and wakefulness. High level of PREG-S (10 and 20 ng) increased paradoxical sleep and slow wave sleep together with an increase of delta power and a decrease of theta power during wakefulness. Dependent on the doses used, PREG-S thus can promote paradoxical sleep alone or the global propensity to fall asleep, impairing the quality of wakefulness. These results unveil a new regulation pathway for PPT neurons and strengthen the role of PREG-S in sleep-wakefulness regulation.

  • Individual differences in cognitive aging: implication of Pregnenolone Sulfate.
    Progress in Neurobiology, 2003
    Co-Authors: Willy Mayo, Marc Pallarès, Muriel Darnaudéry, Michel Le Moal, Jean Bouyer, Olivier George, Sònia Darbra, Monique Vallée, Valérie Lemaire-mayo, Pier Vincenzo Piazza
    Abstract:

    In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the Pregnenolone Sulfate (PREG-S). Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging and severely altered in human neurodegenerative pathologies like Alzheimer’s disease. In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep–wakefulness cycle, and particularly the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young animals. Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer’s disease, have also been related to alterations of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator properties of this steroid at the GABAA receptor level. Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.

  • The Neurosteroid Pregnenolone Sulfate Increases Cortical Acetylcholine Release: A Microdialysis Study in Freely Moving Rats
    Journal of Neurochemistry, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Muriel Koehl, Willy Mayo
    Abstract:

    The effects of Pregnenolone Sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.

  • The neurosteroid Pregnenolone Sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.
    Brain Research, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Pier Vincenzo Piazza, Willy Mayo
    Abstract:

    The effects of an infusion of the neurosteroid Pregnenolone Sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that Pregnenolone Sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.

Muriel Darnaudéry - One of the best experts on this subject based on the ideXlab platform.

  • Individual differences in cognitive aging: implication of Pregnenolone Sulfate.
    Progress in Neurobiology, 2003
    Co-Authors: Willy Mayo, Marc Pallarès, Muriel Darnaudéry, Michel Le Moal, Jean Bouyer, Olivier George, Sònia Darbra, Monique Vallée, Valérie Lemaire-mayo, Pier Vincenzo Piazza
    Abstract:

    In humans and animals, individual differences in aging of cognitive functions are classically reported. Some old individuals exhibit performances similar to those of young subjects while others are severely impaired. In senescent animals, we have previously demonstrated a significant correlation between the cognitive performance and the cerebral concentration of a neurosteroid, the Pregnenolone Sulfate (PREG-S). Neurotransmitter systems modulated by this neurosteroid were unknown until our recent report of an enhancement of acetylcholine (ACh) release in basolateral amygdala, cortex and hippocampus induced by intracerebroventricular (i.c.v.) or intracerebral administrations of PREG-S. Central ACh neurotransmission is known to be involved in the regulation of memory processes and is affected in normal aging and severely altered in human neurodegenerative pathologies like Alzheimer’s disease. In the central nervous system, ACh neurotransmission is also involved in the modulation of sleep–wakefulness cycle, and particularly the paradoxical sleep (PS). Relationships between paradoxical sleep and memory are documented in the literature in old animals in which the spatial memory performance positively correlates with the basal amounts of paradoxical sleep. PREG-S infused at the level of ACh cell bodies (nucleus basalis magnocellularis, NBM, or pedunculopontine nucleus, PPT) increases paradoxical sleep in young animals. Finally, aging related cognitive dysfunctions, particularly those observed in Alzheimer’s disease, have also been related to alterations of mechanisms underlying cerebral plasticity. Amongst these mechanisms, neurogenesis has been extensively studied recently. Our data demonstrate that PREG-S central infusions dramatically increase neurogenesis, this effect could be related to the negative modulator properties of this steroid at the GABAA receptor level. Taken together these data suggest that neurosteroids can influence cognitive processes, particularly in senescent subjects, through a modulation of ACh neurotransmission associated with paradoxical sleep modifications; furthermore, our recent data suggest a critical role for neurosteroids in the modulation of cerebral plasticity, mainly on hippocampal neurogenesis.

  • The Neurosteroid Pregnenolone Sulfate Increases Cortical Acetylcholine Release: A Microdialysis Study in Freely Moving Rats
    Journal of Neurochemistry, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Muriel Koehl, Willy Mayo
    Abstract:

    The effects of Pregnenolone Sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.

  • The neurosteroid Pregnenolone Sulfate infused into the medial septum nucleus increases hippocampal acetylcholine and spatial memory in rats.
    Brain Research, 2002
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Pier Vincenzo Piazza, Willy Mayo
    Abstract:

    The effects of an infusion of the neurosteroid Pregnenolone Sulfate into the medial septum on acetylcholine release in the hippocampus and on spatial memory were evaluated in two experiments. Results show that Pregnenolone Sulfate enhanced acetylcholine release by more than 50% of baseline and improved recognition memory of a familiar environment. Therefore, our results suggest that the septo-hippocampal pathway could be involved in the promnesic properties of this neurosteroid.

  • Pregnenolone Sulfate increases hippocampal acetylcholine release and spatial recognition
    Brain Research, 2000
    Co-Authors: Muriel Darnaudéry, Michel Le Moal, Pier Vincenzo Piazza, Muriel Koehl, Willy Mayo
    Abstract:

    The Pregnenolone Sulfate is a neurosteroid with promnesic properties. Recently, a correlation between endogenous levels of Pregnenolone Sulfate in the hippocampus and performance in a spatial memory task has been reported in aged rats. Cholinergic transmission is known to modulate memory processes and to be altered with age. In the present experiment we investigated the effect of increasing doses of Pregnenolone Sulfate on hippocampal acetylcholine release. Our results show that intracerebroventricular administrations of this neurosteroid induced a dose-dependent increase in acetylcholine release. Administration of 12 and 48 nmol of Pregnenolone Sulfate induced a short lasting (20 min) enhancement of acetylcholine output with a maximum around 120% over baseline and the administration of 96 and 192 nmol doses induced a long-lasting (80 min) increase that peaked around 300% over baseline. In a second experiment we have observed that the 12 nmol dose enhanced spatial memory performance, whereas the 192 nmol dose was inefficient. These results are consistent with previous work suggesting that, a modest increase in acetylcholine release facilitates memory processes, while elevation beyond an optimal level is ineffective. Nevertheless, neurosteroids may be of value for reinforcing depressed cholinergic transmission in certain age-related memory disorders.

  • The promnesic neurosteroid Pregnenolone Sulfate increases paradoxical sleep in rats.
    Brain Research, 1999
    Co-Authors: Muriel Darnaudéry, Marc Pallarès, Michel Le Moal, Jean Bouyer, Willy Mayo
    Abstract:

    Abstract The effect of systemic administration of the neurosteroid Pregnenolone Sulfate (PREG-S) on sleep–wakefulness cycle and on spatial memory performances was investigated in male Sprague–Dawley rats. In the first experiment, the effect of PREG-S administration (saline, 4.75, 47.5 mg/kg, i.p.) on 24 h EEG recording was evaluated. In the second experiment, spatial memory performance in a two-trial memory task was evaluated after post-acquisition administration of similar doses of PREG-S as in the first experiment. Results show that PREG-S increases paradoxical sleep and improves the performance on the memory task yielding similar dose response curves. Starting 4 h after administration of 47.5 mg/kg PREG-S, paradoxical sleep is increased for 10 h. The PREG-S effect on spatial memory lasts for at least 24 h after injection. These results suggest that an enhancement of paradoxical sleep may be involved in the promnesic effects of this neurosteroid.

Luboslav Stárka - One of the best experts on this subject based on the ideXlab platform.

  • sex and age related changes in epitestosterone in relation to Pregnenolone Sulfate and testosterone in normal subjects
    The Journal of Clinical Endocrinology and Metabolism, 2002
    Co-Authors: Helena Havlikova, Martin Hill, Richard Hampl, Luboslav Stárka
    Abstract:

    Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor Pregnenolone Sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone Sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with Pregnenolone Sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty ...

  • Sex- and age-related changes in epitestosterone in relation to Pregnenolone Sulfate and testosterone in normal subjects.
    The Journal of Clinical Endocrinology & Metabolism, 2002
    Co-Authors: Helena Havlikova, Martin Hill, Richard Hampl, Luboslav Stárka
    Abstract:

    Epitestosterone has been demonstrated to act at various levels as a weak antiandrogen. So far, its serum levels have been followed up only in males. Epitestosterone and its major circulating precursor Pregnenolone Sulfate and T were measured in serum from 211 healthy women and 386 men to find out whether serum concentrations of epitestosterone are sufficient to exert its antiandrogenic actions. In women, epitestosterone exhibited a maximum around 20 yr of age, followed by a continuous decline up to menopause and by a further increase in the postmenopause. In men, maximum epitestosterone levels were detected at around 35 yr of age, followed by a continuous decrease. Pregnenolone Sulfate levels in women reached their maximum at about age 32 yr and then declined continuously, and in males the maximum was reached about 5 yr earlier and then remained nearly constant. Epitestosterone correlated with Pregnenolone Sulfate only in males. In both sexes a sharp decrease of the epitestosterone/T ratio around puberty occurred. In conclusion, concentrations of epitestosterone and Pregnenolone Sulfate are age dependent and, at least in prepubertal boys and girls, epitestosterone reaches or even exceeds the concentrations of T, thus supporting its role as an endogenous antiandrogen. The dissimilarities in the course of epitestosterone levels through the lifespan of men and women and its relation to Pregnenolone Sulfate concentrations raise the question of the contribution of the adrenals and gonads to the production of both steroids and even to the uniformity of the mechanism of epitestosterone formation.

  • Rapid Immunoassay for Pregnenolone Sulfate and Its Applications in Endocrinology
    Collection of Czechoslovak Chemical Communications, 2002
    Co-Authors: Martin Hill, Marie Bicikova, Helena Havlikova, Richard Hampl, J. Klak, Vladimír Pouzar, Luboslav Stárka
    Abstract:

    The importance of Pregnenolone Sulfate (PregS) in human physiology has increased in the last decade in connection with its neuroactivating effect via positive modification of N -methyl-D-aspartate receptors and negative modulation of GABA receptors. Therefore, a novel rapid radioimmunoassay was developed and evaluated for measurement of PregS in body fluids. Given the differences in concentrations of cross-reacting substances in various biological materials, several modifications of the method were elaborated and used. Circulating levels of PregS were measured in serum of normal subjects. In both sexes, the age dependences exhibited maximum values before 30th year of age. For the first time, circulating levels of the hormone were measured in patients with a mixed anxio-depressive disorder, where they significantly exceeded those in controls. Further, the levels of PregS were evaluated in time profiles of women around parturition and compared with those in umbilical blood at delivery. A significantly decreasing time profile of PregS was found in maternal blood. No correlation between maternal and umbilical blood was found indicating its autonomous production in mother and in fetus. In addition, concentrations of PregS were measured in breast cystic fluid where they exceeded those in circulation more than by two orders of magnitude.

  • allopregnanolone Pregnenolone Sulfate and epitestosterone in breast cyst fluid
    Steroids, 2001
    Co-Authors: Marie Bicikova, Irene Szamel, Jaroslava Tallova, Martin Hill, Luboslav Stárka
    Abstract:

    Abstract The risk of breast cancer is 2 to 5 times higher in patients suffering from gross cystic disease. Breast cysts are categorized into two groups (type I and type II) according to the concentration of electrolytes in the cyst fluid. The two types also differ with respect to accumulation of steroids and steroidogenic enzyme activity. In type I cysts a higher risk of breast carcinoma could be expected. Here, we studied a possible relationship between the type of cyst and levels of epitestosterone (an endogenous antiandrogen), allopregnanolone (a product of 5α-reductase activity), and Pregnenolone-Sulfate (an activator of N -methyl- d -asparate receptors). We have found five times higher levels of epitestosterone in BCF in comparison with the circulation. Allopregnanolone levels were similar to those in plasma of women in the luteal phase of the menstrual cycle. Pregnenolone-Sulfate levels in BCF were about two orders of magnitude higher when compared with the circulation. No differences were found in concentrations of the steroids studied between the types of cysts.

David H. Farb - One of the best experts on this subject based on the ideXlab platform.

  • Pregnenolone Sulfate as a Modulator of Synaptic Plasticity
    The FASEB Journal, 2015
    Co-Authors: Kavitha Sugunan, R. K. Singh, Ryan Badolato, Syona Shetty, Mateo Zambrano, Kayla Duval, John Adams, Jennifer I. Luebke, Vidhya Kumaresan, David H. Farb
    Abstract:

    Neurosteroids such as Pregnenolone have been implicated in the pathophysiology of neuropsychiatric disorders such as schizophrenia and cannabinoid addiction (1, 2). Our laboratory discovered that the unique negatively charged steroid Pregnenolone Sulfate (PregS), the product of Pregnenolone metabolism via a single sulfation step, modulates fast excitatory synaptic transmission by potentiating NMDA receptor activity in a fashion that is balanced by AMPA receptor inhibition at micromolar concentrations. We recently reported finding a novel high affinity response to PregS (EC50 = 2 pM) that increases intracellular [Ca2+] and CREB activation in cultured rat cortical neurons. Here, we report that PregS increases glutamate receptor and PSD95 colocalized puncta, presumably on dendritic spines of hippocampal neurons, suggesting that PregS increases surface-postsynaptic AMPARs and NMDARs. Whole cell recordings of primary rat hippocampal neurons revealed that PregS increases the frequency of spontaneous excitatory ...

  • Pregnenolone Sulfate as a modulator of synaptic plasticity.
    Psychopharmacology, 2014
    Co-Authors: Conor C. Smith, Terrell T. Gibbs, David H. Farb
    Abstract:

    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.

  • Nanomolar Concentrations of Pregnenolone Sulfate Enhance Striatal Dopamine Overflow in Vivo
    Journal of Pharmacology and Experimental Therapeutics, 2008
    Co-Authors: Ghazaleh Sadri-vakili, Terrell T. Gibbs, G. C. Janis, R. C. Pierce, David H. Farb
    Abstract:

    The balance between GABA-mediated inhibitory and glutamate-mediated excitatory synaptic transmission represents a fundamental mechanism for controlling nervous system function, and modulators that can alter this balance may participate in the pathophysiology of neuropsychiatric disorders. Pregnenolone Sulfate (PS) is a neuroactive steroid that can modulate the activity of ionotropic glutamate and GABAA receptors either positively or negatively, depending upon the particular receptor subtype, and modulates synaptic transmission in a variety of experimental systems. To evaluate the modulatory effect of PS in vivo, we infused PS into rat striatum for 20 min via a microdialysis probe while monitoring local extracellular dopamine (DA) levels. The results demonstrate that PS at low nanomolar concentrations significantly increases extracellular DA levels. The PS-induced increase in extracellular DA is antagonized by the N -methyl-d-aspartate (NMDA) receptor antagonist, d-AP5 [d-(-)-2-amino-5-phosphonopentanoic acid], but not by the σ receptor antagonist, BD 1063 [1(-)[2-(3,4-dichlorophenyl)-ethyl]-4-methylpiperazine]. The results demonstrate that exogenous PS, at nanomolar concentrations, is able to increase DA overflow in the striatum through an NMDA receptor-mediated pathway.

  • Pregnenolone Sulfate augments NMDA receptor mediated increases in intracellular Ca2+ in cultured rat hippocampal neurons.
    Neuroscience Letters, 1992
    Co-Authors: Robert P. Irwin, David H. Farb, Nicholas J. Maragakis, Michael A. Rogawski, Robert H. Purdy, Steven M. Paul
    Abstract:

    The ability of the neuroactive steroid Pregnenolone Sulfate to alter N-methyl-D-aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry and the Ca2+ sensitive indicator fura-2. Pregnenolone Sulfate (5-250 microM) caused a concentration-dependent and reversible potentiation of the rise (up to approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that occurs when hippocampal neurons are depolarized by high K+ in the presence of the NMDA receptor antagonist CPP. These data suggest that the previously reported excitatory properties of Pregnenolone Sulfate may be due, in part, to an augmentation of the action of glutamic acid at the NMDA receptor.

  • Pregnenolone Sulfate: a positive allosteric modulator at the N-methyl-D-aspartate receptor.
    Molecular pharmacology, 1991
    Co-Authors: Terrell T. Gibbs, David H. Farb
    Abstract:

    The N-methyl-D-aspartate (NMDA) receptor is believed to play a major role in learning and in excitotoxic neuronal damage associated with stroke and epilepsy. Pregnenolone Sulfate, a neurosteroid, specifically enhances NMDA-gated currents in spinal cord neurons, while inhibiting receptors for the inhibitory amino acids glycine and gamma-aminobutyric acid, as well as non-NMDA glutamate receptors. This observation is consistent with the hypothesis that neurosteroids such as Pregnenolone Sulfate are involved in regulating the balance between excitation and inhibition in the central nervous system.