The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Mary J Druse - One of the best experts on this subject based on the ideXlab platform.
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Effects of ethanol and ipsapirone on the expression of genes encoding anti-apoptotic proteins and an antioxidant enzyme in ethanol-treated neurons
Brain Research, 2008Co-Authors: Nuzhath F Tajuddin, Mary J DruseAbstract:Abstract Previously, this laboratory found that apoptosis was augmented significantly in fetal rhombencephalic neurons when they were treated with 50 mM ethanol for 24 h. These changes were associated temporally with a reduction in the phosphatidylinositol 3-kinase (PI3K) pro-survival pathway and in the downstream expression of several NF-κB dependent anti-apoptotic genes. The Serotonin-1A Agonist ipsapirone prevented ethanol-associated apoptosis; it also activated the PI3K → pAkt pro-survival pathway and the expression of specific NF-κB dependent anti-apoptotic genes in ethanol-treated neurons. The present study investigated the temporal effects of both ethanol and ipsapirone on the expression of three NF-κB dependent genes, XIAP , Bcl- xl and catalase ; these genes encode proteins that could potentially attenuate ethanol-induced apoptosis. Catalase activity was also measured. All three genes demonstrated an early activation by ethanol. After a brief treatment with 50 mM ethanol, i.e., 2 to 8 h depending on the gene, the expression of XIAP , Bcl- xl , and catalase was significantly increased, possibly as an initial attempt to survive. An ethanol-associated increase in catalase was followed by a rise in catalase activity. However, when ethanol treatment was continued for a longer time, there was a significant reduction in both XIAP and Bcl- xl . In addition, both catalase expression and activity returned to levels found in unstressed controls. Importantly, treatment with ipsapirone augmented the activity of catalase and the expression of Bcl- xl , XIAP , and catalase in ethanol-treated neurons at later time points. The latter effects are likely to contribute to the pro-survival effects of ipsapirone.
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the Serotonin 1A Agonist ipsapirone prevents ethanol associated death of total rhombencephalic neurons and prevents the reduction of fetal Serotonin neurons
Developmental Brain Research, 2004Co-Authors: Mary J Druse, Nuzhath F Tajuddin, Roberta A Gillespie, Elizabeth L Dickson, Mohammed Atieh, Constance A Pietrzak, Phong T LeAbstract:Abstract Previously, this laboratory showed that in utero and in vitro ethanol exposure significantly reduces developing Serotonin (5-HT) neurons and that treatment with a 5-HT1A Agonist such as buspirone or ipsapirone prevents the ethanol-associated loss. The present study investigated whether ethanol decreases fetal rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also investigated whether ipsapirone prevents the ethanol-associated deficit of fetal rhombencephalic neurons by reducing apoptosis. The results of these studies strongly suggest that the ethanol-associated reduction in fetal rhombencephalic neurons that accompanies both in utero and in vitro exposure to physiological concentrations of ethanol is associated with increased apoptosis in these neurons. A physiological concentration of ethanol (i.e., 50 mM) increases apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons. It also appears that the 5-HT1A Agonist ipsapirone provides neuroprotection to these neurons by reducing apoptosis. Another mechanism by which ethanol-associated apoptosis can be blocked is by including serum proteins in the media at a concentration of 1% or higher; this concentration of serum proteins is high in comparison to the protein concentration in cerebrospinal fluid.
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potential involvement of s100b in the protective effects of a Serotonin 1A Agonist on ethanol treated astrocytes
Developmental Brain Research, 2001Co-Authors: Jason L Eriksen, Mary J DruseAbstract:Abstract Previously, this laboratory found that the offspring of rats that consumed ethanol on a chronic basis prior to parturition exhibited a significant reduction in Serotonin (5-HT) neurons and in astrocytes proximal to these neurons. This laboratory also showed that maternal treatment with a 5-HT1A Agonist during the latter part of gestation prevented the reduction of 5-HT neurons and most of the astrocyte abnormalities. The present in vitro studies extended our prior in vivo work by examining the potential involvement of S100B with the protective effects of a 5-HT1A Agonist, i.e., buspirone, on astrocytes. Astrocyte cultures were either maintained in chemically defined media in the presence and absence of ethanol and buspirone or in conditioned media that was generated by ethanol- and buspirone-treated astrocytes. A mouse monoclonal antibody to S100B was used to assess the potential involvement of S100B with the protective effects of buspirone. Additional in vitro studies measured the direct effects of S100B and ethanol on astrocyte proliferation. These investigations demonstrate that in vitro ethanol exposure reduces the number of astrocytes, and that treatment with the 5-HT1A Agonist buspirone prevents the ethanol-associated reduction in astrocyte number. The protective effects of buspirone appear to be mediated by factors that are secreted by astrocytes; such factors likely include S100B. In addition, added S100B prevents an ethanol-associated reduction in [3H]-thymidine incorporation into proliferating astrocytes.
Mitchel S Berger - One of the best experts on this subject based on the ideXlab platform.
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actions of kavain and dihydromethysticin on ipsapirone induced field potential changes in the hippocampus
Human Psychopharmacology-clinical and Experimental, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mitchel S BergerAbstract:The kava-pyrones kavain and dihydromethysticin are constituents of Piper methysticum which possess muscle relaxant, anticonvulsant, analgesic and anxiolytic properties. In the present study the effect of both kava-pyrones were tested on field potential changes induced by the Serotonin-1A Agonist ipsapirone in the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. Ipsapirone induced positive field potential changes which were decreased in amplitude by the Serotonin-1A antAgonist NAN. The ipsapirone response was reduced by extracellular administration of kavain and dihydromethysticin in a dose-dependent manner down to 22·2 and 33·6%, respectively. It is suggested that kavain and dihydromethysticin modulate Serotonin-1A receptor activity which may be of importance in the anti-anxiety action of kava-pyrones. © 1997 John Wiley & Sons, Ltd.
Jorg Walden - One of the best experts on this subject based on the ideXlab platform.
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Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review.
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2001Co-Authors: Heinz Grunze, Jorg Von Wegerer, Jens M. Langosch, K. Schirrmacher, Dieter Bingmann, Jorg WaldenAbstract:Abstract 1. Antiepileptic drugs that are successful as mood stabilizers, e.g. carbamazepine, valproate and lamotrigine, exhibit a characteristic pattern of action on ion fluxes. As a common target, they all affect Na+- and Ca2+ inward and K+ outward currents. 2. Furthermore, they have a variety of interactions with the metabolism and receptor occupation of biogenic amines and excitatory and inhibitory amino acids, and, by this, also influence long- term potentiation (LTP) to different degrees. 3. The kava pyrones (±)-kavain and dihydromethysticin are constituents of Piper methysticum . Anticonvulsant, analgesic and anxiolytic properties have been described in small open trials. 4. In the studies summarized in this article the effects mainly of (±)-kavain were tested on neurotransmission and especially on voltage gated ion channels. It is assumed that effects on ion channels may significantly contribute to clinical efficacy. 5. Experimental paradigms included current and voltage clamp recordings from rat hippocampal CA 1 pyramidal cells and dorsal root ganglia as well as field potential recordings in guinea pig hippocampal slices. 6. The findings suggest that (i) kava pyrones have a weak Na+ antAgonistic effect that may contribute to their antiepileptic properties (ii) that they have pronounced L- type Ca2+ channel antAgonistic properties and act as an positive modulator of the early K+ outward current. These two actions may be of importance for mood stabilization. (iii) Furthermore, kava pyrones have additive effects with the Serotonin-1A Agonist ipsapirone probably contributing to their anxiolytic and sleep- inducing effects. (iv) Finally, they show a distinct pattern of action on glutamatergic and GABAergic transmission without affecting LTP. The latter, however, seems not to be true for the spissum extract of Kava where suppression of LTP was observed. 7. In summary, kava pyrones exhibit a profile of cellular actions that shows a large overlap with several mood stabilizers, especially lamotrigine.
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effects of kawain and dihydromethysticin on field potential changes in the hippocampus
Progress in Neuro-psychopharmacology & Biological Psychiatry, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mathias Berger, Heinz GrunzeAbstract:Abstract 1. 1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg 2+ , recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 μmol/1 and 10 to 40 μmol/1, respectively. 4. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 μmol/1 kawain and 10 μmol/1 dihydromethysticin indicated additive actions of both drugs. 5. 5. Since the Serotonin-1A Agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic Serotonin-1A Agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.
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actions of kavain and dihydromethysticin on ipsapirone induced field potential changes in the hippocampus
Human Psychopharmacology-clinical and Experimental, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mitchel S BergerAbstract:The kava-pyrones kavain and dihydromethysticin are constituents of Piper methysticum which possess muscle relaxant, anticonvulsant, analgesic and anxiolytic properties. In the present study the effect of both kava-pyrones were tested on field potential changes induced by the Serotonin-1A Agonist ipsapirone in the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. Ipsapirone induced positive field potential changes which were decreased in amplitude by the Serotonin-1A antAgonist NAN. The ipsapirone response was reduced by extracellular administration of kavain and dihydromethysticin in a dose-dependent manner down to 22·2 and 33·6%, respectively. It is suggested that kavain and dihydromethysticin modulate Serotonin-1A receptor activity which may be of importance in the anti-anxiety action of kava-pyrones. © 1997 John Wiley & Sons, Ltd.
Ute Winter - One of the best experts on this subject based on the ideXlab platform.
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effects of kawain and dihydromethysticin on field potential changes in the hippocampus
Progress in Neuro-psychopharmacology & Biological Psychiatry, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mathias Berger, Heinz GrunzeAbstract:Abstract 1. 1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg 2+ , recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 μmol/1 and 10 to 40 μmol/1, respectively. 4. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 μmol/1 kawain and 10 μmol/1 dihydromethysticin indicated additive actions of both drugs. 5. 5. Since the Serotonin-1A Agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic Serotonin-1A Agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.
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actions of kavain and dihydromethysticin on ipsapirone induced field potential changes in the hippocampus
Human Psychopharmacology-clinical and Experimental, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mitchel S BergerAbstract:The kava-pyrones kavain and dihydromethysticin are constituents of Piper methysticum which possess muscle relaxant, anticonvulsant, analgesic and anxiolytic properties. In the present study the effect of both kava-pyrones were tested on field potential changes induced by the Serotonin-1A Agonist ipsapirone in the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. Ipsapirone induced positive field potential changes which were decreased in amplitude by the Serotonin-1A antAgonist NAN. The ipsapirone response was reduced by extracellular administration of kavain and dihydromethysticin in a dose-dependent manner down to 22·2 and 33·6%, respectively. It is suggested that kavain and dihydromethysticin modulate Serotonin-1A receptor activity which may be of importance in the anti-anxiety action of kava-pyrones. © 1997 John Wiley & Sons, Ltd.
Jorg Von Wegerer - One of the best experts on this subject based on the ideXlab platform.
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Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review.
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2001Co-Authors: Heinz Grunze, Jorg Von Wegerer, Jens M. Langosch, K. Schirrmacher, Dieter Bingmann, Jorg WaldenAbstract:Abstract 1. Antiepileptic drugs that are successful as mood stabilizers, e.g. carbamazepine, valproate and lamotrigine, exhibit a characteristic pattern of action on ion fluxes. As a common target, they all affect Na+- and Ca2+ inward and K+ outward currents. 2. Furthermore, they have a variety of interactions with the metabolism and receptor occupation of biogenic amines and excitatory and inhibitory amino acids, and, by this, also influence long- term potentiation (LTP) to different degrees. 3. The kava pyrones (±)-kavain and dihydromethysticin are constituents of Piper methysticum . Anticonvulsant, analgesic and anxiolytic properties have been described in small open trials. 4. In the studies summarized in this article the effects mainly of (±)-kavain were tested on neurotransmission and especially on voltage gated ion channels. It is assumed that effects on ion channels may significantly contribute to clinical efficacy. 5. Experimental paradigms included current and voltage clamp recordings from rat hippocampal CA 1 pyramidal cells and dorsal root ganglia as well as field potential recordings in guinea pig hippocampal slices. 6. The findings suggest that (i) kava pyrones have a weak Na+ antAgonistic effect that may contribute to their antiepileptic properties (ii) that they have pronounced L- type Ca2+ channel antAgonistic properties and act as an positive modulator of the early K+ outward current. These two actions may be of importance for mood stabilization. (iii) Furthermore, kava pyrones have additive effects with the Serotonin-1A Agonist ipsapirone probably contributing to their anxiolytic and sleep- inducing effects. (iv) Finally, they show a distinct pattern of action on glutamatergic and GABAergic transmission without affecting LTP. The latter, however, seems not to be true for the spissum extract of Kava where suppression of LTP was observed. 7. In summary, kava pyrones exhibit a profile of cellular actions that shows a large overlap with several mood stabilizers, especially lamotrigine.
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effects of kawain and dihydromethysticin on field potential changes in the hippocampus
Progress in Neuro-psychopharmacology & Biological Psychiatry, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mathias Berger, Heinz GrunzeAbstract:Abstract 1. 1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2. 2. In the present study the effect of these kava-pyrones were tested on field potential changes (fp) induced by omission of the extracellular Mg 2+ , recorded from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. These fp are generated by an activation of NMDA receptors and voltage dependent calcium channels. 3. 3. Kawain and dihydromethysticin reduced reversibly the frequency of occurrence of fp in a concentration range from 5 to 40 μmol/1 and 10 to 40 μmol/1, respectively. 4. 4. Reduction of the fp frequency after addition of subthreshold concentrations of 5 μmol/1 kawain and 10 μmol/1 dihydromethysticin indicated additive actions of both drugs. 5. 5. Since the Serotonin-1A Agonist ipsapirone also exerts anxiolytic effects, subthreshold concentrations of kawain or dihydromethysticin were combined with a subthreshold concentration of ipsapirone in another set of experiments. Combining kawain and ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of fp to 0.76 and 0.81 of the baseline value, respectively. 6. 6. The findings suggest that (i) single constituents of Piper methysticum may have additive actions, (ii) that the two components kawain and dihydromethysticin may enhance the effects of the anxiolytic Serotonin-1A Agonist ipsapirone and (iii) that activation of NMDA receptors and/or voltage dependent calcium channels may be involved in the elementary mechanism of action of some kava-pyrones.
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actions of kavain and dihydromethysticin on ipsapirone induced field potential changes in the hippocampus
Human Psychopharmacology-clinical and Experimental, 1997Co-Authors: Jorg Walden, Jorg Von Wegerer, Ute Winter, Mitchel S BergerAbstract:The kava-pyrones kavain and dihydromethysticin are constituents of Piper methysticum which possess muscle relaxant, anticonvulsant, analgesic and anxiolytic properties. In the present study the effect of both kava-pyrones were tested on field potential changes induced by the Serotonin-1A Agonist ipsapirone in the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs. Ipsapirone induced positive field potential changes which were decreased in amplitude by the Serotonin-1A antAgonist NAN. The ipsapirone response was reduced by extracellular administration of kavain and dihydromethysticin in a dose-dependent manner down to 22·2 and 33·6%, respectively. It is suggested that kavain and dihydromethysticin modulate Serotonin-1A receptor activity which may be of importance in the anti-anxiety action of kava-pyrones. © 1997 John Wiley & Sons, Ltd.
