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)

Interleukin-1 is present in the central nervous system (CNS) during acute and chronic pathological processes. In the present study, we examined the interaction between recombinant human interleukin-1 beta (rhIL-1 beta) and the voltage-dependent calcium (Ca2+) current using the whole-cell patch clamp technique. RhIL-1 beta depressed the voltage-gated Ca2+ current in acutely dissociated guinea pig hippocampal CA1 neurons. This depression is rapid and is observed at pathophysiological concentrations (greater than or equal to 1.97 pg/10 microliters). Concomitant application of rhIL-1 beta and rhIL-1 receptor antagonist had no effect indicating neuroactive specificity of rhIL-1 beta. The depression of the inward Ca2+ current by IL-1 beta may play a role in: 1) the regulation of neuronal excitability; 2) the induction of neurological manifestations during disease; and 3) in the induction and/or progression of neurodegenerative processes.
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PMID:Interleukin-1 beta depresses calcium currents in CA1 hippocampal neurons at pathophysiological concentrations. 152 75

1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.
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PMID:Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats. 152 79

Quantitative autoradiography was used to evaluate the effects of adrenalectomy (ADX) and corticosterone (CORT) on binding at 5-HT1A and 5-HT1B receptors in the dorsal hippocampus and cortex of the rat. ADX increased binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin at 5-HT1A receptors in the oriens and lacunosum moleculare layers of CA2 and CA3, in the lacunosum moleculare layer of CA4 region, and in the dentate gyrus. In restraint-stressed ADX rats, binding was increased only in the oriens and lacunosum moleculare layers of CA2. Restoration of baseline levels of CORT reversed the effects of ADX on 5-HT1A receptors in the hippocampus, while high levels of CORT decreased binding at 5-HT1A receptors in the dentate gyrus. No treatment affected binding at 5-HT1A receptors in the CA1 region of the hippocampus or in the cortex. ADX increased binding of [125I]iodocyanopindolol at 5-HT1B receptors in the infrapyramidal dentate, but this effect was not observed in ADX rats that were restrained. CORT treatment in both ADX and SHAM (adrenally intact) rats resulted in binding at 5-HT1B receptors that was lower than that in untreated ADX and SHAM rats in the infrapyramidal dentate, and lower than that in ADX rats in the suprapyramidal dentate and CA4. In ADX and SHAM rats, CORT also reduced binding at 5-HT1B receptors in area 2 of the cortex. It is suggested that decreases in binding at 5-HT1A and 5-HT1B/1D receptors resulting from chronic exposure to high levels of CORT may also occur in animals that fail to adapt to chronic severe stress. Such changes in binding may play important roles in the etiology of depression.
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PMID:Autoradiographic analyses of the effects of adrenalectomy and corticosterone on 5-HT1A and 5-HT1B receptors in the dorsal hippocampus and cortex of the rat. 153 16

In urethane-anesthetized rats, stimulation of the contralateral hippocampal CA1 region resulted in activation of the homotopic CA1 region. Current-source-density analysis revealed that both basal and apical dendrites were activated. However, alveolar and stratum oriens stimulation in CA1 gave about equal peak excitation of the basal and apical dendrites while CA1 stratum radiatum/moleculare and CA3c stimulation gave stronger apical than basal dendritic excitation. In chronically implanted and freely moving rats, tetanic patterned stimulation of the contralateral CA1, irrespective of depth, resulted in a robust long-term potentiation of the ipsilateral CA1 basal dendritic synapse. The population basal dendritic excitatory postsynaptic potential was initially potentiated to greater than 200% of the baseline and decayed with a 3 h time constant; it lasted at least two days. Patterned stimulation of the commissural inputs at 2 x threshold stimulus intensity seldom potentiated the apical dendritic synapse in CA1; rather, long-term depression was sometimes observed. After tetanic stimulations at 3 x threshold, a small potentiation of the apical dendritic excitation was seen in about half of the experiments. The average apical dendritic potentiation peaked at about 25% and persisted to at least one day. This study provides original evidence that the properties of long-term potentiation are different at the commissural basal dendritic and apical dendritic synapses in CA1 of the behaving rat. Basal dendritic potentiation is low-threshold, high-amplitude and decayed rapidly in the first 3 h. Apical dendritic potentiation is high-threshold, low-amplitude and not rapidly decaying. A long-lasting enhancement of synaptic transmission has been postulated as a physiological correlate of memory. This paper reports properties of this synaptic enhancement for two different types of synapses on the same cells in the behaving animal. The basal dendritic synapse on hippocampal pyramidal cells readily increased their efficacy, up to at least two days, after a brief, patterned stimulation. In the same preparation, it was difficult to obtain a long-lasting increase in the apical dendritic excitation, in contrast to studies on isolated hippocampal slices in vitro.
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PMID:Long-term potentiation induced by patterned stimulation of the commissural pathway to hippocampal CA1 region in freely moving rats. 158 26

The membrane currents responsible for the sustained potential shifts associated with electrographic seizures and with spreading depression in hippocampus were studied in the anesthetized rat. Probes incorporating 16 sensors in a straight line, spaced at 150-microns distances, were recording the potential changes with DC-coupled amplifiers in CA1 and dentate gyrus (DG) of one hemisphere. Seizures and spreading depression were provoked by repetitive stimulation of different afferent pathways. Seizures always began in DG before CA1, regardless of the pathway stimulated. Tonic seizures were associated with a sustained negative potential shift that was largest in the cell body layers. Current source density was computed from these recordings and confirmed the presence of a current sink limited to the cell body layer throughout the duration of electrographic seizures. Spreading depression was associated with a very large sink located in the layer of apical dendrites, maximal among the proximal segment of dendrites, to which the cell body layer served as a source. We conclude that seizures are associated with an inward current in neuron cell bodies, probably flowing through membrane channels of as yet no know physiological function.
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PMID:Current source density of sustained potential shifts associated with electrographic seizures and with spreading depression in rat hippocampus. 161 32

We report here some physiological and pharmacological characteristics of noxious stimuli-induced changes in the hippocampal CA1 pyramidal cell synaptic excitability to field CA3 stimulation. A noxious heat stimulus applied to the left hind paw (LHP) produced a persistent depression of the CA1 population spike (PS) which habituated to a repetition of the stimulus. Interestingly, exposure of the tail to a noxious stimulus following habituation of the LHP produced a depression of the CA1 PS. This finding suggested that persistent depression and habituation are topographically represented. In separate experiments we determined that while the persistent depression of the CA1 population spike was accompanied by, in most cases, a prolonged increase in the amplitude of the CA1 antidromic field potential, there was a concurrent persistent depression and habituation of the CA1 PS and the corresponding apical dendritic field excitatory postsynaptic potential (dfEPSP). This suggested that noxious stimulus-induced CA1 synaptic depression is mediated at the apical dendritic region, perhaps postsynaptically at the dendrites and/or presynaptically on CA3 afferent terminals. Furthermore, atropine sulfate (40 mg/kg ip), which prevented the depression of the CA1 PS, also blocked the depression of dfEPSP when iontophoresed at the apical dendritic recording site. In addition atropine antagonized the depression of the dfEPSP produced by iontophoretic acetylcholine (Ach) but not gamma-aminobutyric acid. However, iontophoretic atropine at the cell body recording site did not prevent the depression of the CA1 PS. These results are consistent with the notion that Ach release in the apical dendrites of CA1 pyramidal cells following a noxious stimulus depresses CA1 synaptic excitability.
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PMID:Responses in the CA1 region of the rat hippocampus to a noxious stimulus. 161 85

In rat hippocampal tissue slices we recorded extracellular potential (Vo) and whole-cell patch clamp current of CA1 pyramid cells. During hypoxic spreading depression (SD)-like depolarization, the holding current (Ih) increased sharply. Membrane 'slope' resistance (Rm) decreased to 10-67% (mean 39%) of the resting value. The SD-related membrane current (ISD) reversed near zero mV. With voltage dependent K+ and Na+ currents blocked by Cs+ and QX-314, shifts of Ih and decrease of Rm during SD were not suppressed. We conclude that hypoxic SD of CA1 pyramidal cells is associated with a large non-selective inward current through yet to be identified membrane mechanisms, which cannot fully explain the SD-related Vo shift.
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PMID:Whole-cell membrane current and membrane resistance during hypoxic spreading depression. 162 73

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.
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PMID:Alterations in the properties of hippocampal pyramidal neurons in the aged rat. 163 Jun 25

The distribution of inositol 1,4,5-trisphosphate (InsP3) 3-kinase was studied in the adult rat brain, using polyclonal antibodies raised against the purified 50,000-Da rat brain enzyme by immunohistochemistry and Western blot, in addition to enzymatic assay. Immunohistochemically, the enzyme was detected in neurons, where it was localized in the dendrites and at the periphery of the cell bodies. Using selective toxin lesions, the highest enzyme levels were found in the dendrites of hippocampal CA1 pyramidal cells and in neurons in the dorsal portion of the lateral septum, regions both involved in long-term potentiation; and in the dendrites of Purkinje cell subpopulations in the cerebellum, a region involved in long-term depression. High levels were found in neurons in the cortex; in the anterior olfactory nucleus; in the striatum (caudate, putamen, olfactory tubercle, Calleja islets and accumbens); in the central nucleus of the amygdala; in the hippocampal dentate gyrus and in the subiculum. The enzyme was not detected in other brain regions. By Western blot, a 50,000-Da immunoreactive band was present in the cortex, caudate-putamen and cerebellum. This band was most highly stained in the hippocampus. InsP3 3-kinase activity, stimulated by calcium/calmodulin, corresponded to 6172-2638 pmol of InsP4 produced/min/mg protein in the hippocampus followed by frontal and parietotemporal cortex and cerebellum. This activity was below 400 in the brainstem and spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inositol 1,4,5-trisphosphate 3-kinase distribution in the rat brain. High levels in the hippocampal CA1 pyramidal and cerebellar Purkinje cells suggest its involvement in some memory processes. 164 40

Pyramidal neurons in area CA1 of the septal hippocampus degenerate 2-3 days after an episode of transient global cerebral ischemia. The purpose of this study was to investigate synaptic transmission and passive neuronal properties in the post-ischemic period prior to neuronal death. Electrophysiological recordings were made from area CA1 in hippocampal slices prepared from rats which had survived a period of 20 min of ischemia for up to 5 days. In septal slices, field responses were in area CA1 unaltered up to 24 h after the ischemic insult. Forty-eight hours after ischemia, the mean amplitude of the population spike, but not the field-EPSP, was significantly reduced. In septal slices prepared more than 48 h after ischemia field potentials were absent or strongly attenuated, whereas they were intact in slices prepared from the temporal pole. No spontaneous discharges were detected in slices prepared at any time from post-ischemic rats. Intracellular recordings were obtained from slices up to 48 h after the ischemic episode. There was no significant difference in the resting membrane potential or input resistance between these neurons and those from control slices. Action potentials followed by a fast afterhyperpolarization and spike accommodation were preserved in all post-ischemic neurons. In all neurons investigated, orthodromic stimulation evoked an EPSP followed by a fast- and then a slow-IPSP. One hour after ischemia, the slow-IPSP was reduced. Forty-eight hours after ischemia, the fast-IPSP was significantly increased. The EPSP was markedly attenuated by the non N-methyl-D-aspartate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). The residual depolarizing component was amplified by perfusing with Mg(2+)-free medium and blocked by the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid. Paired-pulse facilitation of the EPSP was also preserved. As in control slices, the slow-IPSP and paired-pulse depression of the fast-IPSP were blocked by 1 microM baclofen. The present experiments provide no evidence that overt alteration of excitatory synaptic transmission or neuronal properties favouring hyperexcitability precede the ischemically induced death of CA1 pyramidal cells.
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PMID:Electrophysiological recordings from rat hippocampus slices following in vivo brain ischemia. 165 85


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