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)

The prefrontal cortex has been reported to be involved in the regulation of emotional behaviour by integrating cognitive, emotional and autonomic information processes, and impairments of its functions are implicated in psychopathologies such as depression. Neuronal functioning in the prefrontal cortex is under the control of the noradrenergic and the serotonergic system which are both activated during stress. The present study aimed to quantify the effect of chronic psychosocial stress on alpha2-adrenoceptors, beta-adrenoceptors, and serotonin1A receptors in the prefrontal cortex. Male tree shrews (Tupaia belangeri) were subjected to subordination stress for 2, 10, 21 and 28 days, and binding sites for the alpha2-adrenergic antagonists 3H-rauwolscine and 3H-RX821002, for the beta-adrenergic antagonist 125I-iodocyanopindolol, and for the 5-hydroxytryptamine (5HT)1A receptor agonist 3H-8-hydroxy-2-(di-n-propylamino)tetralin were quantified by in vitro receptor autoradiography. Chronic psychosocial stress induced time-dependent receptor down- and upregulations. Beta-adrenoceptors were transiently reduced in numbers after just 2 days of psychosocial stress which is interpreted as agonist-mediated downregulation induced by high local concentrations of noradrenaline released from terminals originating from the locus coeruleus. Alpha2-adrenoceptors were transiently downregulated after 10 days, and upregulated after 28 days of psychosocial stress. These data indicate that the noradrenergic system adapts to the stress by counterbalancing its receptor numbers. 5HT1A receptors were only downregulated after 28 days of psychosocial stress, and thus react later than the noradrenergic receptors. In summary, our results show that monoaminergic receptors in the prefrontal cortex of tree shrews undergo dynamic changes during chronic psychosocial stress. These alterations probably have an impact on neuronal activity, and might contribute to the behavioural changes which have been previously described in subordinate male tree shrews.
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PMID:Monoamine receptors in the prefrontal cortex of Tupaia belangeri during chronic psychosocial stress. 904 67

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

Opioid-induced respiratory depression is well documented. However, exact sites of action and mechanisms for opioid-induced effects on respiration have not yet been elucidated. The present study was carried out on isolated brainstem-spinal cord preparations from newborn rats in order to explore the opioid activity on brainstem mu-, delta- and kappa-receptors. The brainstem-spinal cord was isolated from 0- to 4-day-old Sprague-Dawley rats. The preparation was perfused with artificial cerebrospinal fluid (28.5 degrees C) equilibrated with 95% O2 and 5% CO2 at a pH of 7.4. Neuronal respiratory activity was recorded from the ventrolateral part of the medulla oblongata and efferent impulses from C4 or C5 ventral roots. Effects of the mu-receptor agonist DAGO, the delta-receptor agonist DPDPE and the kappa-receptor agonist U50,488 on respiratory frequency (fR), inspiratory time (Ti) and peak integrated C4 amplitude (Int[C4]) were measured. In addition, the effect of pre-treatment with the mu1 receptor antagonist naloxanazine (35 mg/kg, subcutaneous injection) was evaluated. DAGO reduced fR and Ti in a concentration-dependent manner and caused a reduction of Int(C4) at high concentrations (10 microM). The mu1 receptor antagonist naloxanazine shifted the fR concentration-response curve for DAGO to the right (P < 0.05). DPDPE had no effect on respiratory activities whereas U50,488, like DAGO, reduced fR and Int(C4) in a concentration-dependent manner. It was concluded that mu-opioid receptors, including the mu1 were involved in fR reduction whereas kappa-opioid receptors were involved in reduction of both fR and respiratory amplitude. Delta-opioid receptors do not seem to participate in respiratory modulation at this age.
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PMID:Actions of opioids on respiratory activity via activation of brainstem mu-, delta- and kappa-receptors; an in vitro study. 946 96

The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.
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PMID:Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. 948 70

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

Despite the enormous scientific efforts that have been made to clarify the pathophysiology of ischemic neuronal injury, the mechanism responsible for neuronal cell death after ischemia remains unclear. Neuronal injury can be roughly classified into three categories: acute ischemic injury, delayed neuronal death and neuronal injury in the penumbra. Flow disturbance known as the noreflow phenomenon and postischemic hypoperfusion is the first limiting factor for neuronal resuscitation after an ischemic insult. Extracorporeal circulation has been tried in an attempt to prevent this blood flow disturbance, but it has become apparent that this is no more effective than conventional resuscitation. Delayed neuronal death seems to be triggered by short exposure to ischemia. Although a molecular mechanism including "glutamate excitotoxicity" has been proposed to explain this phenomenon, the details are still uncertain. The interventional point underlying the protective effect of hypothermia against delayed neuronal death may be the key to understanding its pathophysiology. Neuronal death in the penumbra seems to show deterioration through a mechanism of repeated depolarization "spreading depression", although spreading depression itself has no harmful effect on neurons. The pathophysiological mechanism of spreading depression in combination with flow restriction and other relevant factors related to ischemia remains to be investigated.
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PMID:[The pathophysiology of ischemic neuronal injury: an overview]. 969 85

In the previous paper we have demonstrated, by means of field potential and extracellular unit recordings, that bicuculline-induced seizures, which include spike-wave (SW) or polyspike-wave (PSW) complexes, are initiated intracortically and survive ipsilateral thalamectomy. Here, we used multisite field potential and extracellular recordings to validate the patterns of cortical SW/PSW seizures in chronically implanted, behaving cats. To investigate the cellular patterns and excitability during spontaneously occurring and electrically elicited cortical seizures, we used single and dual intracellular recordings from regular-spiking (RS) and fast-rhythmic-bursting (FRB) cortical neurons, in conjunction with field potential recordings from neocortex and related thalamic nuclei, in cats maintained under ketamine-xylazine anesthesia. 1) Invariably, the spontaneous or electrically induced seizures were initiated within the cortex of both behaving and anesthetized animals. Spontaneously occurring, compound seizures consisting of SW/PSW complexes at 2-4 Hz and fast runs at 10-15 Hz, developed without discontinuity from the slow (mainly 0.5-0.9 Hz), sleeplike, cortically generated oscillation. 2) During SW/PSW complexes, RS neurons discharged spike trains during the depth-negative component of the cortical "spike" component of field potentials and were hyperpolarized during the depth-positive field wave. The FRB neurons fired many more action potentials than RS cells during SW/PSW complexes. Averaged activities triggered by the spiky field potentials or by the steepest slope of depolarization in cortical neurons demonstrated similar relations between intracellular activities and field potentials during sleep and seizure epochs, the latter-being an exaggeration of the depolarizing and hyperpolarizing components of the slow sleep oscillation. 3) During the fast runs, RS cells were tonically depolarized and discharged single action potentials or spike doublets (usually with pronounced spike inactivation), whereas FRB cells discharged rhythmic spike bursts, time locked with the depth-negative field potentials. 4) Neuronal excitability, tested by depolarizing current pulses applied throughout the seizures and compared with pre- and postseizure epochs, showed a decreased number of evoked action potentials during both seizure components (SW/PSW complexes and fast runs), eventually leading to null responses during the postictal depression. 5) Data suggest that interconnected FRB neurons may play an important role in the initiation of cortical seizures. We discuss the similarities between the electrographic patterns described in this study and those found in different forms of clinical seizures.
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PMID:Spike-wave complexes and fast components of cortically generated seizures. II. Extra- and intracellular patterns. 974 52

Neuronal plasticity can be defined as adaptive changes in structure and function of the nervous system, an obvious example of which is the capacity to remember and learn. Long-term potentiation and long-term depression are the experimental models of memory in the central nervous system (CNS), and have been frequently utilized for the analysis of the molecular mechanisms of memory formation. Extensive studies have demonstrated that various kinases and phosphatases regulate neuronal plasticity by phosphorylating and dephosphorylating proteins essential to the basic processes of adaptive changes in the CNS. These proteins include receptors, ion channels, synaptic vesicle proteins, and nuclear proteins. Multifunctional kinases (cAMP-dependent protein kinase, Ca2+/phospholipid-dependent protein kinase, and Ca2+/calmodulin-dependent protein kinases) and phosphatases (calcineurin, protein phosphatases 1, and 2A) that specifically modulate the phosphorylation status of neuronal-signaling proteins have been shown to be required for neuronal plasticity. In general, kinases are involved in upregulation of the activity of target substrates, and phosphatases downregulate them. Although this rule is applicable in most of the cases studied, there are also a number of exceptions. A variety of regulation mechanisms via phosphorylation and dephosphorylation mediated by multiple kinases and phosphatases are discussed.
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PMID:Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation. 988 50

Two juvenile sibling male Muntjak deer (Muntiacus muntjak) with histories of depression, ataxia, circling and visual deficits were studied. Cerebrospinal fluid analyses revealed vacuolated macrophages that contained long parallel needle-like intracytoplasmic inclusions. Light microscopically, nerve cell bodies throughout the brain, ganglion cells within the retina and neurons in the myenteric plexuses were variably swollen and had pale granular to finely vacuolated eosinophilic cytoplasm. Neuronal cytoplasm stained specifically with sudan black and Luxolfast blue stains. Within the brain there were occasional axonal spheroids, foci of astrogliosis and scattered microglial cells with abundant pale foamy cytoplasm. Electron microscopy of the brain and retina revealed numerous neurons and ganglion cells, respectively, with multiple membrane-bound structures that contained compact electron-dense membranous whorls and fewer parallel membranous stacks. Thin layer chromatography of total lipid extracts of the cerebral cortex of both cases revealed massive accumulation of G(M2) ganglioside. Crude kidney extracts of the two affected deer were able to hydrolyze 4-methylumbelliferyl beta-GlcNAc, but not 4-methylumbelliferyl beta-GlcNAc-6-sulfate, indicating the defect of beta-hexosaminidase A. Cellogel electrophoresis of the kidney extracts also revealed the deficiency of beta-hexosaminidase A in the two deer. It is concluded that these two deer had the biochemical lesion identical to that of human type B G(M2) gangliosidosis (classical Tay-Sachs disease).
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PMID:Naturally occurring GM2 gangliosidosis in two Muntjak deer with pathological and biochemical features of human classical Tay-Sachs disease (type B GM2 gangliosidosis). 993 Aug 95

We have previously identified three distinct populations of CA1 pyramidal neurons after reperfusion based on differences in synaptic response, and named these late depolarizing postsynaptic potential neurons (enhanced synaptic transmission), non-late depolarizing postsynaptic potential and small excitatory postsynaptic neurons (depressed synaptic transmission). In the present study, spontaneous activity and membrane properties of CA1 neurons were examined up to 48 h following approximately 14 min ischemic depolarization using intracellular recording and staining techniques in vivo. In comparison with preischemic properties, the spontaneous firing rate and the spontaneous synaptic activity of CA1 neurons decreased significantly during reperfusion; spontaneous synaptic activity ceased completely 36-48 h after reperfusion, except for a low level of activity which persisted in non-late depolarizing postsynaptic potential neurons. Neuronal hyperactivity as indicated by increasing firing rate was never observed in the present study. The membrane input resistance and time constant decreased significantly in late depolarizing postsynaptic potential neurons at 24-48 h reperfusion. In contrast, similar changes were not observed in non-late depolarizing postsynaptic potential neurons. The rheobase, spike threshold and spike frequency adaptation in late depolarizing postsynaptic potential neurons increased progressively following reperfusion. Only a transient increase in rheobase and spike threshold was detected in non-late depolarizing postsynaptic potential neurons and spike frequency adaptation remained unchanged in these neurons. The amplitude of fast afterhyperpolarization increased in all neurons after reperfusion, with the smallest increment in non-late depolarizing postsynaptic potential neurons. Small excitatory postsynaptic potential neurons shared similar changes to those of late depolarizing postsynaptic potential neurons. These results suggest that the enhancement and depression of synaptic transmission following ischemia are probably due to changes in synaptic efficacy rather than changes in intrinsic membrane properties. The neurons with enhanced synaptic transmission following ischemia are probably the degenerating neurons, while the neurons with depressed synaptic transmission may survive the ischemic insult.
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PMID:Changes in membrane properties of CA1 pyramidal neurons after transient forebrain ischemia in vivo. 1021 78


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