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)

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

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

The selective vulnerability of pyramidal neurons in the CA1 hippocampal region in ischemic rat brain may be preceded by regional alterations of energy metabolism during early reperfusion. We measured ATP, phosphocreatine (PCr), and glucose in paramedian and lateral CA1 and in an area showing little postischemic cell loss, CA2. ATP levels in paramedian CA1 were depressed immediately after 30 min of ischemia (P less than or equal to 0.02) and remained abnormal after 2 hr of reperfusion (P less than or equal to 0.05). PCr was reduced substantially in both subdivisions of CA1 immediately after ischemia (P less than or equal to 0.04) but returned to normal levels after 2 hr. Glucose levels were depressed in paramedian CA1 and CA2 after ischemia (P less than or equal to 0.02) but corrected with reperfusion. We determined approximately P, the sum of ATP and PCr, in separate experiments investigating regional differences in consumption of high-energy phosphate metabolites during complete ischemia. The approximately P levels of rats subjected to 30 min of reversible ischemia followed by 2 hr of reperfusion showed a different pattern of regional differences from those seen in sham-ischemic animals (P less than or equal to 0.01), indicating a persistent depression of metabolic rate in CA1 during reperfusion. We conclude that regional depletion of high-energy phosphates and alteration of metabolic rate may contribute to the selective vulnerability of the CA1 region during brain ischemia.
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PMID:Regional depletion of adenosine triphosphate, phosphocreatine, and glucose in ischemic hippocampus. 322 10

Intracellular recordings from CA1 and CA2/3 neurons in rats under urethane anesthesia revealed the following effects of medial septal stimulation (10 pulse trains at approximately 100 Hz): (1) in most cases only minimal signs of any synaptic potential; (2) a marked and prolonged (200-500 ms) depression of on-going inhibitory postsynaptic potentials (IPSPs), particularly evident when IPSPs were reversed by Cl- injection; (3) a corresponding increase in input resistance: (4) depolarization when recording with non-Cl(-)-containing electrodes; (5) a predominant hyperpolarization when recording with Cl(-)-containing electrodes; and (6) a marked reduction of the variability of resistance and voltage data. These observations indicate that septal stimulation can strongly depress tonic inhibition in the hippocampus. Septal trains also tended to weaken IPSPs evoked in pyramidal cells by fimbrial stimulation, reducing conductance increase during IPSPs by an average of 42% (S.D. +/- 24.3). Septal inputs to the hippocampal CA1 and CA2/3 regions appear to have a major disinhibitory function.
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PMID:Septohippocampal disinhibition. 334 25

In rats under urethane anesthesia, single shock or tetanic stimulation of the medial septum--which evoked only minimal field potentials--sharply enhanced population spikes evoked in area CA1 by commissural stimulation. An enhancement of population spikes was observed only (a) in areas CA1 and CA2 (adjacent to CA1 in the dorsal hippocampus), but not in the fascia dentata or the deep pyramidal layers CA3 or CA4; (b) in a narrow range of depth, close to the stratum pyramidale; (c) when the intensity of commissural stimulation was of adequate intensity. A comparable facilitation of population spikes was produced at the same sites by microiontophoretic release of acetylcholine. The septal facilitatory action increased in effectiveness with the number of tetanic pulses (up to 10-12) at a given frequency, and it had a maximum at frequencies of 50-100 Hz. It reached a maximum 20-50 ms after the end of septal stimulation, and then decayed slowly, the overall duration being up to 300 ms. The cholinergic nature of the facilitation induced by septal stimulation was confirmed by the parallel potentiation of septal action and that of acetylcholine by physostigmine and their depression by atropine and scopolamine.
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PMID:Electrophysiological and pharmacological characteristics of facilitation of hippocampal population spikes by stimulation of the medial septum. 629 79

Depression of GABA-mediated IPSPs has been proposed to be a crucial factor in the onset of epileptiform activity in most models of epilepsy. To test this idea, we studied epileptiform activity induced by bath application of the excitatory neurotoxin kainic acid (KA) in the rat hippocampal slice. Repetitive field potential firing, spontaneous or evoked, occurred during exposure to KA. Intracellular records from 52 CA1 pyramidal cells during changes from control saline to saline containing 1 microM KA indicated that KA depolarized cells an average of about 5 mV and caused a 15% decrease in input resistance. Action potentials and current-induced burst afterhyperpolarizations did not change significantly. In several cells the tonic effects of KA were preceded by a transient phase of sporadic, spontaneous depolarizations of 2 to 10 mV and 50 to 200 msec duration. These phasic depolarizations were blocked by hyperpolarization. The major effect of 1 microM KA was a depression of synaptic potentials. Initially, KA depressed fast GABA-mediated IPSPs and slow, non-GABA-mediated late hyperpolarizing potentials to 23% and 40% of control values, respectively. IPSP depression correlated closely with onset of burst potential firing in response to synaptic stimulation. Similar observations were made on six cells from the CA2/3 region, although these cells were affected by lower doses of KA. The mechanism of IPSP depression was studied by using KCl-filled electrodes to invert spontaneous IPSPs and make them readily visible. In nine CA1 cells the rate and amplitude of spontaneous IPSPs transiently increased but then decreased in conjunction with evoked IPSP depression. Possible KA effects on postsynaptic GABA responses were investigated by applying GABA locally to cells. KA did not significantly affect GABA responses. Prolonged exposure of CA1 cells to KA in doses of 1 microM or higher depressed intracellularly and extracellularly recorded EPSPs and all field potential activity. This depression was not apparently due to depolarization block in CA1, however. We conclude that KA induces epileptiform activity in hippocampus principally by a presynaptic block of IPSP pathways.
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PMID:Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. 672 34

This study was undertaken to investigate the effect of chronic treatment with fluoxetine, a selective serotonin uptake inhibitor used widely in the treatment of depression, on the distribution and density of 5-HT uptake sites, 5-HT2 receptors, and vesicular amine uptake sites in rat brain. Fluoxetine (10 mg/kg i.p.) was administered daily for 21 days. The density of 5-HT uptake sites labelled by [3H]paroxetine, 5-HT2 receptors labelled by [3H]ketanserin in presence of tetrabenazine and vesicular amine uptake sites labelled by [3H]ketanserin in the presence of mianserin were measured by quantitative autoradiography in 22 areas of rat brain, using coronal tissue sections. Chronic administration of fluoxetine produced significant increases in the density of 5-HT uptake sites in layers of frontoparietal cortex (by 32-43%), of striate cortex (by 55%), in CA1 field of hippocampus (by 111%) and in superior colliculus (by 20%). Fluoxetine treatment also resulted in upregulation of 5-HT2 receptors in layers of frontoparietal cortex (31-38%) and in CA2-3 fields of hippocampus (by 39%). The density of tetrabenazine-sensitive vesicular amine uptake sites in the caudate-putamen was also significantly increased (by 66%). The observed alterations in 5-HT uptake site and 5-HT2 receptor densities are likely a part of adaptive neuronal changes that occur after chronic administration of fluoxetine and may be related to the antidepressant effect of the drug.
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PMID:Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: an autoradiographic study. 824 54

The metabotropic glutamate receptors (mGluRs) can be classified into three families based on amino acid sequence homology, signal transduction mechanisms and pharmacological properties. Generally, class I mGluRs mediate an excitation of neurons while activation of class II and III mGluRs results in a depression of synaptic transmission. In this study we have analyzed the expression pattern of mGluRs in human hippocampus using a panel of polyclonal antibodies specific for mGluR1b, mGluR2/3, mGluR4a, and mGluR5. Immunoreactivity for mGluR1b and mGluR5, i.e., the subtypes representing class I mGluRs, was found in all hippocampal neurons. The mGluR1b antiserum stained perikarya and proximal dendrites, whereas immunoreactivity for mGluR5 was also detectable in the distal dendritic compartments. Immunoreactivity for mGluR2/3, members of class II mGluRs, was present in all principle neurons in the dentate gyrus as well as in the CA4, CA3 and CA2 regions. Pyramidal cells of the CA1 region exhibited only weak labeling for mGluR2/3. Glial cells were also mGluR2/3-immunoreactive. The reaction obtained with an antiserum directed against mGluR4a, a member of class III mGluRs, was confined to the mossy fiber projection field in CA3 stratum lucidum. These data demonstrate differential expression of mGluR variants in the human hippocampus and may provide an important basis for future studies of mGluRs under various neuropathological conditions such as temporal lobe epilepsy, ischemia and neurodegenerative disorders.
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PMID:Immunohistochemical distribution of metabotropic glutamate receptor subtypes mGluR1b, mGluR2/3, mGluR4a and mGluR5 in human hippocampus. 893 Mar 27

A novel concussive-like brain injury (CLBI) model characterized by transient neurobehavioral depression, short duration of brain edema, and long-lasting memory deficits has been reported in our companion paper. This was achieved by dropping a 21-g weight from a height of 25 cm onto the head of a mouse. In the present study, we examined the histopathological changes in this model. Male ddY mice were subjected to either the trauma or sham injury. Gross pathological examination of the brain 1 h posttrauma did not demonstrate subdural, subarachnoid, intraventricular, periventricular, and intraparenchymatous hemorrhage, focal lesions or contusions. Microscopic examination 24 h posttrauma with Nissl staining (cresyl violet), however, revealed a selective bilateral neuronal cell loss in the cerebral cortex and hippocampus but not in the regions of the thalamus, cerebellum, and brain stem. The characteristics of neuronal cell loss in the cortex suggested that this pathology was related in part, to the head impact dynamics, since the cell loss was noted in the central portion of the supraventricular cerebral cortex (p < 0.001), the site of the weight impact, gradually decreasing peripheral to this site, and disappearing in the areas remote from this locus. In contrast, neuronal cell loss seen in the hippocampus did not suggest that this pathology was directly associated with the impact site. Neuronal cell loss was concentrated in the pyramidal cell layer of CA2 (p < 0.01) and CA3 (p < 0.01), and a lesser degree was noted in the subfields of CA3c (p < 0.05) and the hilar region (p < 0.05) but not in the subfields of CA1 and the dentate gyrus layers. The present study characterized the histopathological change seen in the CLBI model, demonstrating the selective neuronal cell loss following weight-drop concussion in mice.
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PMID:A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus. 942 57

Traumatic brain injury (TBI) induces neuronal cell loss in area CA3 of the hippocampus. However, it has not yet been established why traumatic injury of the cortex induces neuronal damage in more remote areas. Spreading depression (SD) may be one potential mechanism for this pathophysiology. The present study evaluated whether SD on the cortex evokes a pathological change in the hippocampus. Forty-two Fisher rats were assigned to four groups: Group I: sham operation (n = 7), Group II: right carotid occlusion (UO) for 7 days (n = 7), Group III: repeated induction of SD by KCl application on dura for 7 days (n = 7), Group III' for 3 h (n = 7), Group IV: SD induction and UO for 7 days (n = 14) Group IV' for 3 h (n = 7). In 5 out of 7 animals in Groups III' and IV', cerebral blood flow (CBF) was monitored using laser Doppler flowmetry for 3 h during the passage of SD. The brains were processed for immunohistochemical analysis of microtubule-associated protein 2 (MAP2). Reactive hyperemia induced by SD was not significantly suppressed by right carotid occlusion (194 +/- 25% and 181 +/- 42% UO in Groups III and IV, respectively). In 6 out of 7 animals in a 7-day model of Group IV, and 3 animals in a 7-day model of Group III, MAP2 depletion in the CA3 area of the hippocampus (partly including CA2) was observed, although no change in the hippocampus was observed in other groups. In conclusion, SD in combination with UO yielded reproducible lesions in CA3. Neuronal injury in the hippocampus after brain trauma may be attributable to SD in combination with the blood flow restriction.
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PMID:Spreading depression induces depletion of MAP2 in area CA3 of the hippocampus in a rat unilateral carotid artery occlusion model. 955 73


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