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)

Studies in humans show antidepressant potential for transcranial magnetic stimulation (TMS). We therefore studied TMS in animal models of depression and compared its effects with those of ECS. ECS in rats has several robust behavioral effects, including enhancement of apomorphine-induced stereotypy, reduction of immobility time in the Porsolt swim test, and increases in seizure threshold for subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced apomorphine-induced stereotypy, whereas a single session of TMS did not. Two TMS treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A single TMS treatment markedly reduces the percentage of rats seizing in response to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS treatment itself but not a sub-convulsive electrical stimulus to the brain. Long-term administration of ECS as well as other antidepressant treatments downregulates beta-adrenergic receptors. We found that TMS significantly reduced the density of [3H]CGP-12177 (a radioligand with beta-adrenergic affinity) binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of monoamines in the mechanism of action of antidepressant treatments was investigated in numerous studies. Region-specific changes in the brain steady-state levels, and turnover rates of monoamines were detected 10 s after administration of a single repetitive TMS (rTMS) session. In the striatum and hippocampus, dopamine levels were increased by 25 +/- 1.5% and 18 +/- 0.8%, respectively, but were reduced in frontal cortex and decreased in the striatum and hippocampus in the TMS-treated rats with no change to the midbrain. TMS caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in other brain regions examined in this study. The ability of TMS to induce behavioral and biochemical alterations similar to those of ECS may further support the potential role of TMS as an antidepressant treatment and bring us closer to the understanding of the mechanism of action of TMS.
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PMID:Magnetic stimulation of the brain in animal depression models responsive to ECS. 977 58

Neuropeptide Y (NPY), has been implicated in the pathophysiology of depression and the mechanisms of action of electroconvulsive treatment (ECT). In this series of experiments, we explored whether there are differences between Flinders Sensitive Line (FSL) rats, an animal model of depression, and controls, Flinders Resistant Line (FRL) in (1) baseline brain NPY-LI concentrations, (2) effects of ECS on locomotion and brain neuropeptides, (3) amphetamine effects on behavior, and (4) effects of ECS pretreatment on subsequent effects of amphetamine on behavior. Both strains were divided into two groups, receiving eight ECS or ShamECS. Twenty-four hours after the last session, animals were habituated in activity boxes for 45 min before given d-amphetamine (1.5 mg.kg(-1), subcutaneously) or vehicle. Locomotor activity was then recorded for an additional 45 min. Twenty-four hours later, rats were sacrificed by microwave irradiation, the brains dissected into frontal cortex, occipital cortex, hippocampus, hypothalamus and striatum, and the neuropeptides extracted and measured by radioimmunoassay. No differences between FSL and FRL rats in baseline locomotor activity were found. FSL compared to FRL animals showed a significantly larger locomotion increase following saline and a significantly smaller increase following amphetamine. ECS pretreatment significantly decreased the saline effects on locomotion in the FSL and the amphetamine effects in the FRL rats. 'Baseline' NPY-like immunoreactivity (LI) concentrations were lower in the hippocampus of the 'depressed' rats. ECS increased NPY-LI in frontal cortex, occipital cortex and hippocampus of both strains. The hippocampal NPY-LI increase was significantly larger in the FSL compared to FRL animals.
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PMID:Neuropeptide Y in brains of the Flinders Sensitive Line rat, a model of depression. Effects of electroconvulsive stimuli and d-amphetamine on peptide concentrations and locomotion. 1084 Jan 38

Human and animal studies suggest that neuropeptide Y (NPY), a peptide co-localized and co-released with classical neurotransmitters, is involved in the pathogenesis of affective disorders. In addition, lithium, electroconvulsive treatments (ECT in humans and ECS in rodents) and antidepressants affect NPY in a specific temporal- and brain-region fashion. These results have been obtained on healthy male rats; females and/or "depressed" animals have essentially not been studied. Consequently, we studied brain NPY-like immunoreactivity (-LI) under basal conditions and following a series of ECS in both male and female Flinders Sensitive Line (FSL), an animal model of depression, and their controls, the Flinders Resistant Line (FRL) rats. Furthermore, we examined whether the oestrus cycle affects NPY-LI in these strains. Following sacrifice by focused microwave irradiation, the peptides were extracted from dissected brain regions and measured by radioimmunoassay. Hippocampal NPY-LI in both sexes was significantly lower in the "depressed" FSL compared to the control FRL. ECS increased NPY-LI in both male and female rats in both FSL and FRL strains in hippocampus, frontal cortex and occipital cortex. In the hypothalamus, the increase was found only in the FSL rats. In both FSL and control rats, the basal NPY-LI was lower in the hippocampus of female compared to male rats. NPY-LI did not vary during the different phases of the oestrus cycle. These results suggest that the gender differences are not due to NPY-LI variations during the oestrus. The results are consistent with our hypothesis that NPY plays a role in the pathophysiology of depressive disorders and provide further evidence that one of the modes of ECS action is to elevate NPY in the limbic system. Assumption that gender differences in NPY could explain increased rates of depression in women is speculative, but is in line with the findings in the present study.
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PMID:Neuropeptide Y in male and female brains of Flinders Sensitive Line, a rat model of depression. Effects of electroconvulsive stimuli. 1116 8

Electroconvulsive therapy is considered an effective treatment for severe depression. However, the mechanisms for its long-lasting antidepressant efficacy are poorly understood. In the present study, we investigated changes of the immobility time in the forced swim test and brain-derived neurotrophic factor (BDNF) protein after withdrawal from 14-day repeated electroconvulsive stimuli (ECS, 50 mA, 0.2 s) in rats. Immobility time in the forced swim test was markedly decreased 6 h after withdrawal following 14-day ECS treatment. Thereafter, prolongation of the withdrawal period gradually diminished the decreasing effect of immobility time, but significant effects persisted for up to 3 days after the withdrawal. Locomotor activity in the open-field test increased 6 h after withdrawal from the ECS treatment, and the enhanced effect persisted for at least 7 days. The BDNF protein level in the hippocampus was markedly increased 6 h after the withdrawal, and remained high for at least 7 days. These findings provide further evidence that repeated ECS has long-lasting effect on increase in BDNF and locomotor activity and decrease in immobility time in the forced swim test.
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PMID:Repeated electroconvulsive stimuli have long-lasting effects on hippocampal BDNF and decrease immobility time in the rat forced swim test. 1730 36

Dysregulation of the monoaminergic systems is likely a sufficient but not a necessary cause of depression. A wealth of data indicates that neuropeptides, e.g., NPY, CRH, somatostatin, tachykinins and CGRP play a role in affective disorders and alcohol use/abuse. This paper focuses on NPY in etiology and pathophysiology of depression. Decreased peptide and mRNA NPY were found in hippocampus of both the genetic, e.g., the FSL strain, and environmental rat models of depression, e.g., chronic mild stress and early life maternal separation paradigms. Rat models of alcoholism also show altered NPY. Furthermore, NPY is also reduced in CSF of depressed patients. Antidepressive treatments tested so far (lithium, topiramate, SSRIs, ECT and ECS, wheel running) increase NPY selectively in rat hippocampus and in human CSF. Moreover, NPY given icv to rat has antidepressive effects which are antagonized by NPY-Y1 blockers. The data support our hypothesis that the NPY system dysregulation constitutes one of the biological underpinnings of depression and that one common mechanism of action of antidepressive treatment modalities may be effects on NPY and its receptors. In a novel paradigm, early life maternal separation was superimposed on "depressed" FSL and control rats and behavioral and brain neurochemistry changes observed in adulthood. The consequences were more deleterious in genetically vulnerable FSL. Early antidepressive treatment modulated the adult sequelae. Consequently, if these data are confirmed, the ethical and medical question that will be asked is whether it is permissible and advisable to consider prophylactically treating persons at risk.
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PMID:Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role? 1757 54

Recent studies place emphasis on the modulations of immune system in various psychiatric disorders and/or treatments. The aim of this study was to investigate the implications of immune-related glial cells in a rapid-acting treatment for depression, namely, electroconvulsive therapy (ECT). Specifically, the effects of electroconvulsive shock (ECS; animal model of ECT) on microglia were morphologically determined in the mouse hippocampus by using ionized calcium-binding adaptor molecule 1 (Iba1) immunocytochemistry. For comparison, S100beta-positive astrocytes, another type of glial cells, were also tested. After 24 hours of acute ECS administration, a meshwork of Iba1-positive microglial processes was largely diminished, although the change was transient. In mice that received chronic ECS administration, the decline of Iba1-positive microglial process meshwork continued even 1 month after the last shock. Morphometric image analysis revealed the significant reduction of Iba1-positive microglial process density following ECS administration. On the other hand, neither acute nor chronic ECS administration made alterations in the patterns of expression of S100beta immunoreactivity. No significant changes were detected in the cell surface area of S100beta-positive astrocytes following ECS administration. The optical disector analysis demonstrated that ECS did not affect the numerical densities of Iba1-positive microglia and S100beta-positive astrocytes in the hippocampus. These results provide some key to understand the potential role of microglia and astrocytes in the antidepressant action of ECT.
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PMID:Reduction of Iba1-expressing microglial process density in the hippocampus following electroconvulsive shock. 1853 64

Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings suggest that current directionality, polarity, and electrode configuration influence the efficiency of seizure induction with ECT. Unidirectional stimulation and novel electrode configurations such as FEAST are two approaches to lowering seizure threshold. Furthermore, the impact of FEAST on ictal and post-ictal expression appeared to be polarity dependent. Future studies may examine whether these differences in seizure threshold and expression have clinical significance for patients receiving ECT.
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PMID:Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction. 1922 53

There is an increasing body of evidence suggesting that GABAergic dysfunction is involved in various psychiatric disorders. The goal of our study was to investigate the influences of electroconvulsive therapy (ECT), one of the most effective treatments for depression, on the GABAergic system in the hippocampus. In this stereology-based study, we identified GABAergic neurons by immunostaining for two isoforms of glutamic acid decarboxylase (GAD), GAD65, and GAD67 and estimated the expression changes induced by single or repeated electroconvulsive shock (ECS; an animal model of ECT). The numerical density (ND) of entire population of GABAergic neurons (expressing GAD65 and/or GAD67) was seldom altered by the administration of ECS. GAD67-positive (GAD67(+)) neurons were also rarely affected by ECS. On the other hand, the ND of GAD65(+) neurons was changed in a layer-specific manner. In the CA1 region, the ND of GAD65(+) neurons was increased in the strata radiatum/lacunosum-moleculare (SR/SLM) by repeated ECS. In the CA3 region, the ND of GAD65(+) neurons was decreased in the stratum oriens and SR/SLM after single ECS. The expression ratio of GAD65 in GABAergic neurons was increased specifically in layers receiving afferents from the entorhinal cortex (EC), i.e., SR/SLM of the CA1 region and molecular layer of the dentate gyrus (DG), after repeated ECS administration, whereas the expression ratio of GAD67 in GABAergic neurons was decreased in several layers by the same treatment. These results indicate that the ECS-induced changes in ND of GAD65(+) or GAD67(+) neurons were most likely due to alterations in GAD expression rather than actual increases or decreases in cell numbers. Altogether, the neuronal circuit-dependent alterations in GABA-mediated signaling may play a contributory role in the depression treatment process introduced by ECT.
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PMID:Neuronal circuit-dependent alterations in expression of two isoforms of glutamic acid decarboxylase in the hippocampus following electroconvulsive shock: A stereology-based study. 1928 76

Electroconvulsive therapy (ECT) is a very efficient treatment for severe depression. However, cognitive side effects have raised concern to whether ECT can cause cellular damage in vulnerable brain regions. A few recent animal studies have reported limited hippocampal cell loss, while a number of other studies have failed to find any signs of cellular damage and some even report that electroconvulsive seizures (ECS; the animal counterpart of ECT) has neuroprotective effects. We previously have described gliogenesis in response to ECS. Loss of glial cells is seen in depression and de novo formation of glial cells may thus have an important therapeutic role. Glial cell proliferation and activation is however also seen in response to neuronal damage. The aim of the present study was to further characterize glial cell activation in response to ECS. Two groups of rats were treated with 10 ECS using different sets of stimulus parameters. ECS-induced changes in the morphology and expression of markers typical for reactive microglia, astrocytes and NG2+ glial cells were analyzed immunohistochemically in prefrontal cortex, hippocampus, amygdala, hypothalamus, piriform cortex and entorhinal cortex. We observed changes in glial cell morphology and an enhanced expression of activation markers 2 h following ECS treatment, regardless of the stimulus parameters used. Four weeks later, few activated glial cells persisted. In conclusion, ECS treatment induced transient glial cell activation in several brain areas. Whether similar processes play a role in the therapeutic effect of clinically administered ECT or contribute to its side effects will require further investigations.
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PMID:Glial cell activation in response to electroconvulsive seizures. 1954 Feb 97

As a psychiatric treatment, modern electroconvulsive therapy (ECT) requires anesthesia to enhance safety, but anesthetics may weaken its efficacy. Previous studies have provided inconsistent results and lack satisfactory details of the influence of anesthetics on ECT efficacy, which partially complicates the clinical selection of ECT protocols. To test our hypothesis that anesthetics interact with the intrinsic parameters of ECT to differentially regulate its therapeutic efficacy, we investigated the effects of the anesthetic propofol and the stimulus intensities of ECT on behavior and hippocampal brain-derived neurotrophic factor (BDNF) in a rodent model of depression. After treatment with chronic unpredictable mild stresses to produce the model, the depressed rats received anesthesia with propofol or normal saline, i.p., and electroconvulsive shock (ECS, an analog of ECT to animals) with different stimulus intensities. The sucrose preference and open field tests were performed to assess behavior, and BDNF level in hippocampus was measured with ELISA. We found that propofol regulated the efficacy of ECS differently at different stimulus intensities in both the behavioral and molecular levels. At medium intensities (120 and 180 mC), propofol enhanced the anti-depressant efficacy of ECS without largely compromising the recovering efficacy of ECS on spontaneous exploratory activities. The results indicated that propofol and ECS stimulus intensities interacted and resulted in different regulating efficacies at different intensities. Medium stimulus intensities were optimal for ECS efficacy under propofol anesthesia.
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PMID:Propofol interacts with stimulus intensities of electroconvulsive shock to regulate behavior and hippocampal BDNF in a rat model of depression. 2241 May 90


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