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C Fernando Valenzuela

Publications and source records attributed to C Fernando Valenzuela.

25 records · Page 2Linked to original sources
PubMed2003

Chronic prenatal ethanol exposure alters ionotropic glutamate receptor subunit protein levels in the adult guinea pig cerebral cortex.

BACKGROUND: The superfamily of glutamate-gated ion channels mediates fast excitatory synaptic transmission in the central nervous system and is composed of the NMDA, AMPA, and kainate receptors. Binding studies have shown that chronic prenatal and/or neonatal ethanol exposure produces persistent effects on the numbers of some of these channels. However, whether or not this chronic ethanol exposure produces long-lasting effects on the expression of specific ionotropic receptor subunits remains an open question. METHODS: Timed pregnant Dunkin-Hartley strain guinea pigs received oral administration of one of the following regimens between gestational days 2 and 67: (1) 4 g of ethanol per kilogram of maternal body weight per day with ad libitum access to pellet food and water (ethanol group), (2) isocaloric sucrose- and pair-feeding with ad libitum access to water (sucrose group), or (3) isovolumetric water with ad libitum access to food and water (water group). The maternal blood ethanol concentration produced by the ethanol regimen was 71 +/- 12 mM. Adult offspring were killed on postnatal day 61, and cerebral cortical tissue was analyzed for ionotropic glutamate receptor subunit expression by Western immunoblotting. RESULTS: There was a statistically significant decrease in NR2B subunit protein expression and an increase in GluR2/3 subunit protein expression in the ethanol group. Expression of NR1, NR2A, NR2C, GluR1, GluR6/7, and KA2 subunit proteins was not affected. CONCLUSIONS: These results demonstrate that chronic prenatal ethanol exposure produces long-lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.

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PubMed2003

Neurosteroid modulation of glutamate release in hippocampal neurons: lack of an effect of a chronic prenatal ethanol exposure paradigm.

BACKGROUND: Pregnenolone sulfate (PREGS) is a promnesic neurosteroid that is abundantly expressed in the hippocampus of rodents. Studies have shown that the modulation of postsynaptic ligand-gated ion channels by this neurosteroid is impaired in preparations from the brains of fetal ethanol-exposed animals. In this study, we examined whether the presynaptic actions of PREGS also are affected by exposure to ethanol in utero. METHODS: Rat dams were exposed to one of the following diets during pregnancy: (1) 5% ethanol liquid diet, (2) 0% ethanol liquid diet with pair-feeding, and (3) ad libitum controls. We then studied the presynaptic actions of PREGS on (1) alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) recorded from cultured hippocampal neurons in the whole-cell patch-clamp configuration and (2) paired-pulse facilitation of NMDA receptor-dependent excitatory postsynaptic potentials that were intracellularly recorded from CA1 pyramidal neurons in hippocampal slices from adult rats. RESULTS: Chronic prenatal ethanol exposure affected neither basal mEPSC frequency nor its potentiation by PREGS. Basal paired-pulse facilitation (i.e., in the absence of PREGS) was unaffected by fetal ethanol exposure. Chronic prenatal ethanol exposure did not affect the PREGS-induced potentiation of paired-pulse facilitation. CONCLUSIONS: Chronic prenatal ethanol exposure does not affect the basal probability of glutamate release in immature or mature hippocampal neurons. Moreover, the presynaptic actions of the neurosteroid PREGS also are unaffected by this exposure. Given that modulation of glutamate release could have a role in the mechanism of the promnesic actions of this neurosteroid, future studies are warranted to determine whether PREGS can ameliorate learning and memory deficits in fetal ethanol-exposed animals.

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PubMed2002

Ethanol withdrawal upregulates kainate receptors in cultured rat hippocampal neurons.

We have previously demonstrated that kainate receptors (KA-Rs) are acutely inhibited by ethanol (EtOH). Here we show that KA-Rs are also affected by long-term EtOH exposure. Whole-cell recordings of pharmacologically isolated KA-R-mediated currents in cultured hippocampal neurons revealed that exposure to 80 mM EtOH for 3 days followed by a 24 h withdrawal period increased KA-R current densities. Quantitative confocal microscopy showed that expression of GluR6/7 subunits increases after ethanol withdrawal in these neurons. Since KA-Rs control hippocampal excitability and seizure generation, we postulate that upregulation of these receptors may have a role in the pathophysiology of alcohol withdrawal syndrome.

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PubMed2002

Neurosteroids enhance bandpass filter characteristics of the rat Schaffer collateral-to-CA1 synapse.

Neurosteroids are important modulators of synaptic activity in the mammalian central nervous system. We have shown previously that the neurosteroid, pregnenolone sulfate (PREGS) enhances paired-pulse facilitation at the Schaffer collateral-to-CA1 synapse in rat hippocampal slices. Here we show that PREGS enhances the facilitation of postsynaptic potentials (PSPs) during a 300 ms train of repetitive stimuli at frequencies between 10 and 50 Hz. At higher or lower frequencies, however, PREGS does not affect the PSPs produced by repetitive stimuli. This enhancement of the bandpass filtering characteristic of a central synapse by a naturally occurring neurosteroid could selectively influence transmission at bursting or other highly active synapses.

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PubMed2002

Neurosteroids enhance spontaneous glutamate release in hippocampal neurons. Possible role of metabotropic sigma1-like receptors.

Pregnenolone sulfate (PREGS), one of the most abundantly produced neurosteroids in the mammalian brain, improves cognitive performance in rodents. The mechanism of this effect has been attributed to its allosteric modulatory actions on glutamate- and gamma-aminobutyric acid-gated ion channels. Here we report a novel effect of PREGS that could also mediate some of its actions in the nervous system. We found that PREGS induces a robust potentiation of the frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured hippocampal neurons. PREGS also decreased paired pulse facilitation of autaptic EPSCs evoked by depolarization, indicating that it modulates glutamate release probability presynaptically. PREGS potentiation of mEPSCs was mimicked by dehydroepiandrosterone sulfate and (+)-pentazocine but not by (-)-pentazocine, the synthetic (-)-enantiomer of PREGS or the inactive steroid isopregnanolone. The sigma receptor antagonists, haloperidol and BD-1063, blocked the effect of PREGS on mEPSCs, as did pertussis toxin and the membrane-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl) ester. These results suggest that PREGS increases spontaneous glutamate release via activation of a presynaptic G(i/o)-coupled sigma receptor and an elevation in intracellular Ca2+ levels. We postulate that presynaptic actions of neurosteroids have a role in the maturation and/or maintenance of synaptic networks and the processing of information in the central nervous system.

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PubMed2002

Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.

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