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)

During early postischemic reperfusion, the vulnerable brain regions (e.g., hippocampal CA1) show a relatively high deoxyglucose accumulation. To investigate if this accumulation is a marker for the later-occurring regional cell death and to determine its cellular localization, we studied the glucose metabolism in the CA1 region post ischemia after removal of its pre- or postsynaptic components. A 20-min period of cerebral ischemia was used for selective removal of the main postsynaptic component in CA1 pyramidal cells, and a bilateral intraventricular injection of kainic acid for removal of the majority of presynaptic axon terminals in this region (and postsynaptic terminals and cell bodies in CA3). The glucose metabolism was studied in these two lesion types and in sham-operated animals before and after a period of ischemia. There was a 60% reduction of metabolism after ischemia in the nonvulnerable regions, whereas CA1 and sometimes CA3 showed a columnar pattern of high and low metabolism. CA1 and CA3 devoid of the postsynaptic component showed increased postischemic metabolism. The latter was due to the presence of macrophages, as demonstrated by an enzyme histochemical stain for nonspecific esterase. CA1 with no presynaptic component showed a postischemic depression of the glucose metabolism similar to the rest of the brain. It is suggested that the level of the postischemic glucose metabolism in the ischemia-vulnerable regions is determined by the presence of both synaptic components. The presence of macrophages in a region gives rise to apparently normal values of glucose metabolism.
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PMID:Postischemic glucose metabolism is modified in the hippocampal CA1 region depleted of excitatory input or pyramidal cells. 230 41

1. Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration [( K+]o) changes that occur during spontaneous and evoked spreading depression (SD) episodes. We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting [K+]o, 2) magnitude of the [K+]o change during seizurelike events and SDs, and 3) susceptibility to SD episodes. Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery. We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region. 2. Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in [K+]o. The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and [K+]o undershoots (below the original resting membrane potential and resting [K+]o). 3. During the onset of a SD episode in the CA1 region, the local [K+]o rose either before or at the same time as the membrane potential depolarization. 4. In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes. During these ictallike episodes, [K+]o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures. Increases in [K+]o evoked by repetitive stimulation were regulated at a lower level in CA3 (average [K+]o rise to 11.4 mM) than in CA1 (average [K+]o rise to 18.3 mM). 5. In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl. However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers. 6. A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local [K+]o measured with K-ISMs. The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices. 231 42

The neurotoxic effects of long-term, low-level exposure to the commercially available insecticide, Fenthion, were examined in the present study. Young (2 month) adult, male Long-Evans rats were dermally exposed to Fenthion (25 mg/kg, 3X week) and sampled after 2 and 10 months exposure to assess neurotoxic damage in the hippocampus using morphological and biochemical endpoints. Histopathology, consisting of gliosis, swollen and necrotic neurons, and cell dropout, occurred in the dentate gyrus (DG), CA4 (hilus), and CA3 sectors as early as 2 months postexposure. Acetylcholinesterase (AChE) staining of brain tissues taken at this time was severely reduced in the septal nuclei, the DG molecular layer, the CA4, and the hippocampus proper. After 10 months exposure to Fenthion, cellular necrosis and gliosis intensified in the CA4 and CA3 regions and occasionally involved the CA2. Radiometric assays of AChE activity in the hippocampus indicated a 65 and 85% depression after 2 and 10 months exposure, respectively. Quinuclidinyl benzilate binding for the hippocampal muscarinic receptor was reduced by 6 and 15%, after 2 and 10 months exposure, respectively. A separate group of older (12 month) rats was exposed to the same dosing regimen of Fenthion and examined for neuropathological damage after 2 and 10 months exposure. Aged animals exposed for only 2 months expressed severe hippocampal degeneration in a pattern similar to that seen in the young adult after 10 months exposure (viz., DG, CA4, CA3). Aged animals exposed for 10 months showed more extensive histopathology of the CA4-2 and occasionally CA1. These observations indicate that in both young adult and aged animals, subchronic, low-level exposure to anticholinesterase compounds can result in serious neurotoxic consequences to the mammalian hippocampus.
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PMID:The neurotoxicity of subchronic acetylcholinesterase (AChE) inhibition in rat hippocampus. 238 36

A paired-pulse stimulus protocol was used to measure angular bundle to dentate gyrus paired-pulse inhibition in rats before and after the occurrence of 36 or 72 seizures elicited from the contralateral CA3 region. The seizures showed progressive lengthening. There was a moderate increase in paired-pulse depression 1 h after 36 seizures and a further increase after 72 seizures. These data demonstrate that the same experimental protocol which produced a decrease in paired-pulse inhibition in the CA1 region caused the opposite effect in the dentate gyrus.
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PMID:Repetitive seizures cause an increase in paired-pulse inhibition in the dentate gyrus. 248 90

1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).
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PMID:Anoxia on slow inward currents of immature hippocampal neurons. 255 81

Intracellular recordings were made from electrophysiologically identified inhibitory neurons in the dentate hilus. (-)Baclofen (0.1-0.5 mumol/l), applied by the bath, strongly hyperpolarized inhibitory neurons, reduced their input resistance and induced outward currents under voltage clamp at holding potentials of -60 mV in cells recorded with KCl-filled electrodes. Increasing the (-)baclofen concentration (up to 1 mumol/l) did not increase the amplitude of the outward current, but increased its duration. (-)Baclofen depressed Cl-dependent IPSPs evoked by perforant path stimulation in inhibitory neurons, granule cells and CA3 neurons. In the case of inhibitory neurons and CA3 neurons, depression of IPSPs, membrane hyperpolarization and increase in membrane conductance concurred. All effects were blocked by BaCl2 (1 mmol/l) in the superfusate. In the case of granule cells, depression of IPSPs by (-)baclofen outlasted an only small membrane hyperpolarization, conductance increase or outward current. High concentrations (up to 10 mumol/l) of (-)baclofen depressed evoked IPSPs of granule cells for an extended period of time, but the other effects remained small and transient. IPSPs elicited in granule cells by microdrop application of glutamate to the dentate hilus were also blocked by (-)baclofen, but spontaneous IPSPs were only reduced in amplitude. We suggest that the blockade of GABAA receptor-mediated IPSPs of hippocampal neurons by the GABAB receptor agonist (-)baclofen can be explained by a K-dependent hyperpolarization of inhibitory neurons.
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PMID:Effects of (-)baclofen on inhibitory neurons in the guinea pig hippocampal slice. 256 87

1. Focal electrographic seizures arose in the CA1 region of rat hippocampal slices bathed in elevated (8.5 mM) external potassium [( K+]o). High [K+]o also induced spontaneous interictal bursts that originated in area CA3 and propagated to CA1. To examine the contribution to electrographic seizure initiation of excitatory mechanisms that are influenced by extracellular volume, we studied the effect of hyperosmotic expansion of interstitial volume on seizure occurrence, interictal bursts, and excitatory synaptic transmission. The tissue electrical resistance was also measured leading up to and during seizures. 2. Media made 5-30 mosmol/kg hyperosmotic by addition of agents restricted to the extracellular space (mannitol, sucrose, raffinose, L-glucose, dextran) rapidly and reversibly abolished [K+]o-induced spontaneous CA1 seizures in 86% of slices tested. However, similar increases in osmolality effected by agents that access the intracellular compartment (D-glucose, glycerol) did not influence electrographic seizure occurrence. Hyperosmotic changes with plasma membrane impermeable compounds, but not permeable compounds, produced significant concentration-dependent decreases (1-10%) in the electrical resistance of CA1 stratum pyramidale. Because tissue resistance is proportional to extracellular volume, these results suggest that hyperosmotic suppression of electrographic seizures is associated with expansion of the extracellular space in hippocampal slices. 3. Measurement of electrical resistance of the CA1 stratum pyramidale during spreading depression and electrographic seizure revealed an increase in tissue resistance to 122% and 108% of control, respectively. Furthermore, a slight (approximately 2%) but significant increase in electrical resistance gradually occurred over the 20 s immediately preceding seizure generation. The observed increase in tissue resistance suggests extracellular space is decreased during these events. 4. Hyperosmolality did not alter CA3 interictal burst frequency. However, burst intensity, estimated from the total length of the burst waveform, was significantly reduced in both the CA3 (83% control) and CA1 region (67% control) when osmotic changes were imposed by plasma membrane impermeant compounds. Additionally, media made hypoosmotic by removal of 7.5 mM NaCl reversibly increased burst intensity. 5. High [K+]o potentiated excitatory synaptic transmission and excitatory postsynaptic potential (EPSP) spike coupling.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of extracellular space in hyperosmotic suppression of potassium-induced electrographic seizures. 272 35

The influence was studied of the stimulation of the CA3 field of the dorsal hippocampus on the course of motor polarization dominant created by the action of the direct current on the rabbit's cortical sensorimotor area. It is shown that hippocampus stimulation by 1 mA current (0.5 ms, 100 Hz, 0.2 s) against the background of the dominant optimum elicits its inhibition. It is manifested in depression of the motor "dominant" reaction of the forelimb to testing stimuli and in abolition of coherent connections of theta-range electrical activity of the sensorimotor cortex and CA3 field of the dorsal hippocampus. On the contrary, the hippocampus stimulation by a weak current (30-50 mcA, 0.5 ms, 30 Hz, 0.2 s) during optimum dominant reinforces it, eliciting a movement of the "dominant" limb. Against the background of an unstable dominant it provides for its activation and stabilization and recovers the dominant in the following days during its extinction.
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PMID:[Effect of stimulation of field CA3 in the dorsal hippocampus on the motor polarization dominant in rabbits]. 275 Feb 92

In CA3 pyramidal neurons of guinea pig hippocampal slices an outward current activated by the GABAB agonist, baclofen (0.3 microM, Ibac) was reduced by low concentrations of carbachol (Cch, 0.1-0.3 microM). The effect of Cch desensitized suggesting that the receptor subtype involved in this muscarinic effect of Cch was of the M1 subtype. The receptor subtype was also characterized by its equilibrium dissociation constant for pirenzepine (10 nM) as an M1 receptor. Li+ applied extracellularly (1 mM) or intracellularly blocked the suppression of Ibac by Cch without affecting the Cch blockade of a current termed IAHP, which is mediated by M2 receptors. While the effect of intracellular Li+ application was immediate, it developed very slowly with extracellular application. Since Li+-salts are used effectively in the treatment of mania and depression, the selective effect of Li+ on M1-mediated muscarinic neurotransmission might be important for the cholinergic hypothesis of affective disorders.
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PMID:Lithium discriminates between muscarinic receptor subtypes on guinea pig hippocampal neurons in vitro. 276 60

Antagonistic interactions between cholecystokinin (CCK) and nanomolar concentrations of kainic acid (KA) have been reported in area CA3 of the rat hippocampal slice. This study tested the possibility that kainic acid inhibits the release of CCK. Elevated K+ was found to release CCK from hippocampal slices in a Ca2+-dependent manner. KA, at concentrations as low as 100 nM, inhibited this release by about one-third. Because CCK appears to exert a net inhibitory effect on the firing of CA3 pyramidal cells, the epileptogenic action of KA may be explained, in part, by the depression of CCK release.
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PMID:Kainic acid inhibits cholecystokinin release from rat hippocampal slices. 276 81


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