Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroactive substances reaching the developing brain can affect the formation of the functionality of nervous circuitry. To explain this so-called functional neuroteratology it has been proposed that neurotransmission has persistently been altered. Pharmacological interference with the developing central noradrenergic system in the rat by means of drugs like clonidine, yohimbine and propranolol, indeed revealed lasting changes in the turnover of noradrenaline in several brain areas, but no changes were found in beta-receptor density. It is assumed that either alpha-receptor density is affected or that signal transduction is altered, since electrophysiologically a persistent supersensitivity was found for the noradrenaline-evoked depression of glutamate-evoked firing in e.g. CA1 pyramidal cells of the hippocampus. Elucidation of the underlying neurochemical mechanisms of such lasting effects of perinatal exposure to noradrenergic drugs aims at establishing the role of noradrenaline in development, but also to provide physicians with the possibility to better assess the advantages and disadvantages of drugs to be prescribed during reproduction and, hence, to make the best choice of treatment.
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PMID:Lasting effects of early noradrenergic receptor occupation on brain noradrenaline turnover and on beta-receptors. 196 21

To elucidate the mechanisms involved in the inhibition of synaptic transmission by ammonium ions, the effects of NH4Cl on glutamate release and on synaptic transmission from Schaffer collaterals to CA1 pyramidal cells were measured in fully submerged slices of rat hippocampus. The large, Ca(2+)-dependent release of glutamate evoked by electrical-field stimulation or by 56 mM K+ was not reduced by 5 mM NH4Cl. In contrast, 5 mM NH4Cl decreased the smaller, field stimulation-induced release of glutamate observed in the presence of low concentrations of Ca2+ (0.1 mM), as well as the spontaneous release of glutamate both in normal and low Ca2+. Unlike the Ca(2+)-dependent release of glutamate, synaptic transmission was reversibly depressed even by 1 mM NH4 Cl. Firing of CA1 pyramidal cells evoked by iontophoretically applied glutamate was significantly inhibited by 2 or 5 mM NH4Cl. This depression was increased in the presence of 25 microM bicuculline. Results suggest that ammonium ions do not depress the Ca(2+)-dependent release of glutamate originating from synaptic vesicles, which is involved in synaptic transmission. Rather, ammonium ions inhibit synaptic transmission by a postsynaptic action, a conclusion strengthened by the inhibitory effect of NH4Cl on glutamate-induced firing. However, NH4Cl may inhibit the formation of cytoplasmic glutamate, the source of spontaneous and Ca(2+)-independent release.
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PMID:Neurochemical and electrophysiological studies on the inhibitory effect of ammonium ions on synaptic transmission in slices of rat hippocampus: evidence for a postsynaptic action. 196 24

Preclinical neurochemical studies indicate that buspirone and gepirone bind selectively to presynaptic (dorsal raphe) and postsynaptic (hippocampus, cortex) 5-hydroxytryptamine1A (5-HT1A) receptor binding sites. Furthermore, in functional neurochemical and electrophysiologic receptor studies, azapirones in general display partial agonist activity at postsynaptic 5-HT1A receptors linked negatively to adenyl cyclase and appear to demonstrate a similar profile on hippocampal CA1 pyramidal neurons sensitive to the effects of 5-HT. Through their action at presynaptic 5-HT1A receptors, these agents have been shown to dose-dependently inhibit cortical and hippocampal 5-HT synthesis while inhibiting the firing of 5-HT--containing dorsal raphe neurons, both in vitro and in vivo. These results suggest that the efficacy seen in clinical trials of anxiety and depression may be related to buspirone's and gepirone's complex interaction with presynaptic and postsynaptic 5-HT1A receptors, which initiate long-term changes in central 5-HT neurotransmission.
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PMID:Neurochemistry and neurophysiology of buspirone and gepirone: interactions at presynaptic and postsynaptic 5-HT1A receptors. 197 41

The proposal that long-term potentiation (LTP) is a mechanism underlying memory in the mammalian brain rests on a number of properties of LTP that parallel characteristics of memory defined by behavior. A prominent feature of behaviorally defined memory is its reversibility. LTP is induced at synapses that correlate in their activity, and the signal for induction is calcium influx through N-methyl-D-aspartate (NMDA) receptor channels. By analogy to the reversibility of behaviorially defined memory, uncorrelated synaptic activity might be expected to reverse LTP, an anti-Hebbian effect called long-term depression, which has only recently been described in the hippocampus [Stanton, P. K. & Sejnowski, T. J. (1989) Nature (London) 339, 215-218]. Because the extent to which synaptic activity is correlated is represented by postsynaptic calcium concentrations, it seemed likely to us that long-term depression is related to the failure of calcium to pass through the NMDA channel. One way to block the calcium influx that signals correlated synaptic activity is with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovalerate. We performed a series of experiments in rat hippocampal slices designed to estimate the amount of synaptic depression per afferent test pulse under these conditions. Schaffer collateral-commissural afferents to field CA1 were repetitively stimulated in the presence of 2-amino-5-phosphonovalerate. No enduring synaptic depression nor reversal of LTP could be detected. We conclude that some other mechanism underlies long-term depression in the hippocampus.
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PMID:Failure to reverse long-term potentiation by coupling sustained presynaptic activity and N-methyl-D-aspartate receptor blockade. 197 53

We studied the effects of iontophoretically administered MK-801 (50-150 nA) on ischemic changes on the CA1 hippocampal field potential. Twenty rats under urethane anesthesia, of which the hippocampal field response was depressed or lost upon ligation of the carotid arteries, were used. MK-801 applications starting before carotid ligation, decreased the depression of the field response in 8 of 11 trials. MK-801 was applied after the appearance of ischemic changes and partly restored the deteriorated hippocampal field potential in 16 of 34 penetrations. MK-801 was ineffective in preventing or restoring the severely depressed or lost evoked activity. During ischemia a DC potential shift of -32.6 +/- 3.7 mV (n = 10) was recorded. MK-801 reduced the amplitude of the DC potential shift by 50% when applied before (n = 6) or after (n = 4) the initiation of ischemia. Activation of N-methyl-D-aspartate (NMDA) receptors by glutamate or N-methyl-DL-aspartate (NMDLA) induces a slow negative wave on the field response. During ischemia a similar negative wave spontaneously appeared in 9 trials and was also induced with low currents (5-10 nA) of NMDLA which were insufficient to evoke the NMDA-mediated wave before ischemia. These data provide electrophysiological evidence that NMDA receptors are activated during ischemia and MK-801 reduces ischemia neuronal dysfunction.
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PMID:Electrophysiological evidence for activation of NMDA receptors and its antagonism by MK-801 in cerebral ischemia. 198 Aug 49

Membrane hyperpolarization (increase in resting potential) together with a conductance increase has been suggested as a common mechanism of anesthetic action. The current study compared the effects of halothane, enflurane, and isoflurane on resting membrane potential and conductance of hippocampal CA1 neurons in vitro. At 1 MAC, halothane produced significant (P less than 0.01) hyperpolarization (-2.8 +/- 1.3 mV, mean +/- SD) accompanied by a conductance increase (6.2 +/- 2.7%). Enflurane also produced a significant (P less than 0.001) hyperpolarization (-3.15 +/- 1.2 mV); however, this was accompanied by a conductance decrease (-4.5 +/- 1.5%). Isoflurane produced variable effects. Anesthetic-induced hyperpolarization was maximal in neurons with more negative initial resting potentials and was reduced by depolarization. Across agents, these relatively small changes in resting potential were not correlated with decreases in excitability as measured by synaptically evoked population spike depression. The results are not consistent with a common action of the three agents on a single ionic channel.
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PMID:Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific. 198 63

1. Extracellular [K] and [Ca] were measured with ion-selective microelectrodes in CA1 pyramidal cell layer of rat hippocampal slices in an interface chamber. 2. Near room temperature (21-22 degrees C), brief periods of anoxia (3- to 4-min substitution of 95% N2-5% CO2 for 95% O2-5% CO2) produced very small changes in [K]o [-0.022 +/- 0.10 (SE) mM] or [Ca]o (-0.030 +/- 0.0029 mM) and were associated with only minor depression of population spikes (-22.5 +/- 11%). 3. Stratum radiatum (SR) stimulation (0.2-5 Hz) could evoke substantial increases in [K]o (by 0.2-2 mM); although variable, they were consistent in any one slice. The same stimulation regularly caused only small depressions of [Ca]o (by less than 0.1 mM, typically). 4. Also at 21-22 degrees neither stimulation nor anoxia generated more than minimal reductions in extracellular space [by 2.3 +/- 0.94%, as measured by the tetramethylammonium (TMA) method], and spreading depression (SD) occurred in only 1 out of 20 slices. 5. At 33-34 degrees C, anoxia (also for 3-4 min) consistently produced more substantial increases in [K]o (0.83 +/- 0.18 mM); but the apparent changes in [Ca]o at 33 degrees C (0.058 +/- 0.12 mM) could not with certainty be distinguished from thermoelectric artifacts. There was a severe depression of population spikes (-76 +/- 10%). 6. Although electrical stimulation evoked greater reductions in [Ca]o, increases in [K]o were 50% smaller. 7. During anoxia at 33-34 degrees C, the extracellular space was significantly reduced, by 6.1 +/- 0.9%. Moreover, in 37% of the slices, either stimulation or anoxia triggered massive increases in [K]o (greater than 10 mM) and large reductions in [Ca]o (less than 1 mM), associated with SD-like swings in focal potential. 8. It is concluded that the extracellular ionic changes evoked by brief anoxia do not contribute in a major way to the depression of synaptic transmission.
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PMID:Temperature dependence of extracellular ionic changes evoked by anoxia in hippocampal slices. 201 34

The acute effects of hypoxia and/or hypoglycaemia on DC potentials recorded from CA1 pyramidal neurones of the gerbil hippocampal slice maintained in vitro were investigated. Depolarizing potential changes were recorded when the slice was superfused with the excitatory amino acid agonists: NMDA (N-methyl-D-aspartic acid; 3-30 microM), AMPA ((RS)alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate; 1-30 microM), kainate (3-100 microM) and L-glutamate (1-10 mM). In response to a 20 min period of superfusion with an hypoxic artificial CSF solution at 30 degrees C, a transient depolarization occurred followed by a marked hyperpolarization. A further hyperpolarization occurred when superfusion of the slice with an oxygenated artificial CSF recommenced. Post-hypoxia, when the neurones had repolarized, the response to NMDA (10 microM) was less than the pre-hypoxic response. The extent of the depression of the NMDA response was found to depend on three variables: a) the duration of the period of hypoxia, b) the glucose concentration of the artificial CSF, and c) the temperature of the slice. As the duration of hypoxia was increased, the depression of the NMDA response was more marked. Reduction of the glucose concentration from 11 mM to 2 mM by partial substitution with sucrose (9 mM) made the tissues more sensitive to the effects of hypoxia, whereas reduction of the temperature from 30 degrees C to 20 degrees C made them less sensitive. The depression of the response to NMDA was observed over a range of concentrations of NMDA. The concentration response curve for AMPA was also flattened, however, the depolarizations in response to kainate or GABA were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hypoxia and hypoglycaemia on DC potentials recorded from the gerbil hippocampus in vitro. 209 Sep 52

Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.
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PMID:Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. 211 31

The effects induced by arachidonic acid upon excitatory synaptic transmission were investigated in the CA1 subfield of rat hippocampal slices. Perfusion with medium containing 50 microM of arachidonic acid induced in 12 of 19 experiments a long-lasting potentiation of the stratum radiatum-induced responses recorded in the cell body and in the apical dendritic layers. In 5 of 19 experiments, arachidonic acid evoked a depression of the same responses. Both effects were antagonized by nordihydroguaiaretic acid which is an inhibitor of lipoxygenase enzymes. These results demonstrate that one or more than one of the arachidonic acid metabolites of the lipoxygenase pathways might be involved in the long-term modulation of synaptic transmission in the hippocampus.
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PMID:Long-term changes of synaptic transmission induced by arachidonic acid in the CA1 subfield of the rat hippocampus. 212 31


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