Effects Of Electroconvulsive Shock Research Articles

Effects of electroconvulsive shock on the astroglial alteration in dopamine supersensitivity disorder model rats

Effects of electroconvulsive shock on the astroglial alteration in dopamine supersensitivity disorder model rats

Evaluating the Effect of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Rats

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Evaluating the Safety of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Mice

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Electroconvulsive Shock, but Not Transcranial Magnetic Stimulation, Transiently Elevates Cell Proliferation in the Adult Mouse Hippocampus.

Hippocampal plasticity is hypothesized to play a role in the etiopathogenesis of depression and the antidepressant effect of medications. One form of plasticity that is unique to the hippocampus and is involved in depression-related behaviors in animal models is adult neurogenesis. While chronic electroconvulsive shock (ECS) strongly promotes neurogenesis, less is known about its acute effects and little is known about the neurogenic effects of other forms of stimulation therapy, such as repetitive transcranial magnetic stimulation (rTMS). Here, we investigated the time course of acute ECS and rTMS effects on markers of cell proliferation and neurogenesis in the adult hippocampus. Mice were subjected to a single session of ECS, 10 Hz rTMS (10–rTMS), or intermittent theta burst stimulation (iTBS). Mice in both TMS groups were injected with BrdU 2 days before stimulation to label immature cells. One, 3, or 7 days later, hippocampi were collected and immunostained for BrdU + cells, actively proliferating PCNA + cells, and immature DCX + neurons. Following ECS, mice displayed a transient increase in cell proliferation at 3 days post-stimulation. At 7 days post–stimulation there was an elevation in the number of proliferating neuronal precursor cells (PCNA + DCX +), specifically in the ventral hippocampus. iTBS and rTMS did not alter the number of BrdU + cells, proliferating cells, or immature neurons at any of the post-stimulation time points. Our results suggest that neurostimulation treatments exert different effects on hippocampal neurogenesis, where ECS may have greater neurogenic potential than iTBS and 10–rTMS.

Inhibition of CB1 receptor alleviates electroconvulsive shock-induced memory impairment by regulating hippocampal synaptic plasticity in depressive rats

Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, but it can cause cognitive deficit. Unfortunately, effective preventive measures are still lacking. The endocannabinoid system is thought to play a key role in regulation of cognitive process. Whether the endocannabinoid system is involved in the learning and memory impairment caused by ECS remain unclear. In this work, we first found that cannabinoid receptor type 1 (CB1R) and 2-arachidonoylglycerol (2-AG) were strongly expressed in hippocampus by electroconvulsive shock (ECS) in a rat depression model established by chronic mild stress (CMS). Pharmacological inhibition of CB1R using AM251 in vivo resulted in a pronounced relief in ECS-induced spatial learning and memory impairment as well as in a marked reversal of impaired hippocampal long-term potentiation (LTP), and reduced synapse-related proteins expression. Furthermore, results of sucrose preference test (SPT) and open-field test (OFT) showed that AM251 had no significant impact on the therapeutic effects of ECS on pleasure and psychomotor activity. Taken together, we identified that CB1R is involved in the ECS-induced spatial learning and memory impairment and Inhibition of CB1R facilitates the recovery of memory impairment and hippocampal synaptic plasticity, without interfering with the therapeutic effects of ECS in depressed rats.

Enhancement of morphine-induced antinociception after electroconvulsive shock in mice.

Electroconvulsive therapy (ECT) has been applied for chronic pain for decades. The amounts of opioids to treat pain are sometimes reduced after a series of ECT. The effect of ECT on morphine-induced analgesia and its mechanism underlying the reduction of morphine requirement has yet to be clarified. Therefore, we administered electroconvulsive shocks (ECS) to mice and investigated the antinociceptive effect of morphine in a hot plate test. We examined the expression level of µ-opioid receptor in the thalami of mice 25 h after administration of ECS compared to the thalami of mice without ECS administration using western blotting. ECS disturbed the development of a decrease in the percentage of maximal possible effect (%MPE), which was observed 24 h after a morphine injection, when ECS was applied 25, 23, 21, and 12 h before the second administration of morphine. We also examined the effect of ECS on the dose-response curve of %MPE to morphine-antinociception. Twenty-five hours after ECS, the dose-response curve was shifted to the left, and the EC50 of morphine given to ECS-pretreated mice decreased by 30.1% compared to the mice that were not pretreated with ECS. We also found that the expression level of µ-opioid receptors was significantly increased after ECS administration. These results confirm previous clinical reports showing that ECT decreased the required dose of opioids in neuropathic pain patients and suggest the hypothesis that this effect of ECT works through the thalamus.

Ryanodine receptors are involved in the improvement of depression-like behaviors through electroconvulsive shock in stressed mice

BackgroundElectroconvulsive therapy (ECT) is effective for treating depression. However, the mechanisms underlying the antidepressant effects of ECT remain unknown. Depressed patients exhibit abnormal Ca2+ kinetics. Early stages of the intracellular Ca2+ signaling pathway involve the release of Ca2+ from the endoplasmic reticulum (ER) via Ca2+ release channels. ObjectiveWe considered that depression may be improved via ECT-induced normalization of intracellular Ca2+ regulation through the Ca2+ release channels. The current study aimed to investigate the effects of ECT on two Ca2+ release channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). MethodsA mouse depression-like model subjected to water immersion with restraint stress was administered electroconvulsive shock (ECS) therapy. Their depression-like status was behaviorally and histologically assessed using forced swimming tests, novelty-suppressed feeding tests, and by evaluating neurogenesis in the hippocampal dentate gyrus, respectively. A RyRs blocker, dantrolene, was administered prior to ECS, and the changes in depression-like conditions were examined. ResultsThe protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of the mouse model with depression-like symptoms. This increase was attenuated as depression-like symptoms were reduced due to ECS application. However, pre-injection with dantrolene reduced the antidepressant effects of ECS. ConclusionsA significant increase in RyRs expression in a depression-like state and exacerbation of depression-like symptoms by RyRs inhibitors may be caused by RyRs dysfunction, suggesting overexpression of RyRs is a compensatory effect. Normalization of RyRs expression levels by ECS suggests that ECT normalizes the Ca2+ release via RyRs. Thus, normalizing the function of RyRs may play an important role in the therapeutic effect of ECT.

Electroconvulsive shock restores the decreased coverage of brain blood vessels by astrocytic endfeet and ameliorates depressive-like behavior

BackgroundAlthough growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms. MethodsAfter electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5. ResultsGunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats. ConclusionsECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels.

Changes in synaptic plasticity are associated with electroconvulsive shock-induced learning and memory impairment in rats with depression-like behavior.

BackgroundAccompanied with the effective antidepressant effect, electroconvulsive shock (ECS) can induce cognitive impairment, but the mechanism is unclear. Synaptic plasticity is the fundamental mechanism of learning and memory. This study aimed to investigate the effect of ECS on synaptic plasticity changes in rats with depression-like behavior.MethodsChronic unpredictable mild stress procedure was conducted to establish a model of depression-like behavior. Rats were randomly divided into the following three groups: control group with healthy rats (group C), rats with depression-like behavior (group D), and rats with depression-like behavior undergoing ECS (group DE). Depression-like behavior and spatial learning and memory function were assessed by sucrose preference test and Morris water test, respectively. Synaptic plasticity changes in long-term potentiation (LTP), long-term depression (LTD), depotentiation, and post-tetanic potentiation (PTP) were tested by electrophysiological experiment.ResultsECS could exert antidepressant effect and also induced spatial learning and memory impairment in rats with depression-like behavior. And, data on electrophysiological experiment showed that ECS induced lower magnitude of LTP, higher magnitude of LTD, higher magnitude of depotentiation, and lower magnitude of PTP.ConclusionECS-induced learning and memory impairment may be attributed to postsynaptic mechanism of LTP impairment, LTD and depotentiation enhancement, and presynaptic mechanism of PTP impairment.

Early and late postictal cardiac electrophysiological changes associated with low, moderate, and high dose electroconvulsive shocks.

Studies have examined the effects of electroconvulsive therapy (ECT) on human cardiac electrophysiology. However, no study has so far examined whether these effects vary with the magnitude of the electrical dose used to elicit the seizure. Because the benefits and adverse effects of the ECT seizure are dose-dependent, we examined the effects of different electrical doses of electroconvulsive shocks (ECS) on cardiac electrophysiology in an animal model with a view to determine whether cardiac electrophysiology could be a useful proxy to evaluate the quality of the ECT seizure. Adult female Wistar rats (n = 20/group) received sham, low dose (10 mC), moderate dose (18 mC), or high dose (25 mC) ECS. The electrocardiogram (ECG) was recorded and was analyzed for time and frequency domain variables in 30 s epochs in preictal (30 s before ECS), early postictal (starting 15 s after stimulation) and late postictal (5 h after ECS) periods. ECS was associated with substantial changes in most time and frequency domain measures during the early postictal period; a strong parasympathetic effect was observed. However, the effects of different ECS doses did not differ for any variable. All changes returned to levels that were similar to those of the sham controls in the late postictal period. The effect of ECS on time and frequency domain cardiac electrophysiological measures was not dose-dependent. This suggests that if higher electrical doses are associated with stronger central seizures, ECG-derived variables may not be useful proxies for the quality of the central seizure. The generalization of this conclusion from animal to clinical contexts requires study.

Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat

BackgroundAlthough electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.MethodsThe rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.ResultsWe found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.ConclusionsECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0688-2) contains supplementary material, which is available to authorized users.

The Behavioral Physiology and Antidepressant Mechanisms of Electroconvulsive Shock.

This study aimed to determine whether the association between antidepressant (AD) and anticonvulsant effects of electroconvulsive therapy constitutes a necessary, causal relationship. The rats received corneal kindling to induce an epileptic focus, whereas electroconvulsive shock (ECS) was given antagonistically. The forced swim test (FST; a model of AD efficacy), cumulative kindling scores (indexing epileptogenesis), and clonus duration (measuring anticonvulsant effects) were used to assess the effects of ECS. Intensity and route of administration (corneal vs pinnate) of ECS were varied within or across 2 experiments. Under various conditions, an increase in mobility in the FST (an index of AD properties) was observed in the absence of any retardation of kindling; under other conditions, an antiepileptogenic effect occurred in the absence of any change in immobility in the FST. In addition, 2 forms of ECS treatment had equal AD properties, whereas only 1 of the 2 treatments reduced clonus time (suggesting an elevated seizure threshold). In a rat model, putative AD effects of ECS are dissociable from its antiepileptogenic and anticonvulsant effects, suggesting different stimulus thresholds for the various effects of corneal ECS: the antiepileptogenic effect required a lower current dose than the behavioral effect in the FST, whereas the anticonvulsant effect required the highest stimulation level. With transpinnate ECS, the threshold for the behavioral effect in the FST and the antiepileptogenic threshold were reversed.

Electroconvulsive shocks decrease α2-adrenoceptor binding in the Flinders rat model of depression

Despite years of drug development, electroconvulsive therapy (ECT) remains the most effective treatment for severe depression. The exact therapeutic mechanism of action of ECT is still unresolved and therefore we tested the hypothesis that the beneficial effect of ECT could in part be the result of increased noradrenergic neurotransmission leading to a decrease in α2-adrenoceptor binding.We have previously shown that both the Flinders sensitive line (FSL) and Flinders resistant line (FRL) rats had altered α2-adrenoceptor binding compared to control Sprague–Dawley (SD) rats. In this study, we treated female FSL, FRL and SD rats with electroconvulsive shock (ECS), an animal model of ECT, or sham stimulation for 10 days before brains were removed and cut into 20µm thick sections. Densities of α2-adrenoceptors were measured by quantitative autoradiography in the hippocampus, thalamic nucleus, hypothalamus, amygdala, frontal cortex, insular cortex, and perirhinal cortex using the α2-adrenoceptor antagonist, [3H]RX 821002.ECS decreased the binding of α2-adrenoceptors in cortical regions in the FSL and cortical and amygdaloid regions in the control FRL rats compared to their respective sham treated group. The normal SD controls showed no significant response to ECS treatment. Our data suggest that the therapeutic effect of ECS may be mediated through a decrease of α2-adrenoceptors, probably due to a sustained increase in noradrenaline release. These data confirm the importance of the noradrenergic system and the α2-adrenoceptor in depression and in the mechanism of antidepressant treatments.

Effect of acute and chronic electroconvulsive shock on 5-hydroxytrypamine 6 receptor immunoreactivity in rat hippocampus.

Electroconvulsive shock (ECS) induces not only an antidepressant effect but also adverse effects such as amnesia. One potential mechanism underlying both the antidepressant and amnesia effect of ECS may involve the regulation of serotonin (5-hydroxytryptamine) 6 (5-HT6) receptor, but less is known about the effects of acute ECS on the changes in 5-HT6 receptor expression in the hippocampus. In addition, as regulation of 5-HT receptor expression is influenced by the number of ECS treatment and by interval between ECS treatment and sacrifice, it is probable that magnitude and time-dependent changes in 5-HT6 receptor expression could be influenced by repeated ECS exposure. To explore this possibility, we observed and compared the changes of 5-HT6 receptor immunoreactivity (5-HT6 IR) in rat hippocampus at 1, 8, 24, or 72 h after the treatment with either a single ECS (acute ECS) or daily ECS for 10 days (chronic ECS). We found that acute ECS increased 5-HT6 IR in the CA1, CA3, and granule cell layer of hippocampus, reaching peak levels at 8 h and returning to basal levels 72 h later. The magnitude and time-dependent changes in 5-HT6 IR observed after acute ECS were not affected by chronic ECS. These results demonstrate that both acute and chronic ECS transiently increase the 5-HT6 IR in rat hippocampus, and suggest that the magnitude and time-dependent changes in 5-HT6 IR in the hippocampus appear not to be influenced by repeated ECS treatment.

Electroconvulsive Shock Increases SIRT1 Immunoreactivity in the Mouse Hippocampus and Hypothalamus

Recent study shows that silent mating-type information regulation 2 homolog 1 (SIRT1) regulation may be involved with depression. Electroconvulsive shock (ECS) has been used for the treatment of depression, but little is known about the effect of ECS on the changes in SIRT1 levels in the brain. The present study was designed to observe whether ECS dynamically regulates SIRT1 levels in the hippocampus and hypothalamus; both of these regions have been implicated in the pathophysiology of depression. Male imprinting control region mice were given a single ECS via ear clip electrodes, and then killed 0.5, 2, 8, 24, or 48 hours after ECS. Changes in SIRT1 were observed by Immunohistochemistry, and obtained results were compared with sham controls that did not receive ECS. Silent mating-type information regulation 2 homolog 1 immunoreactivity levels in the CA1 and CA3 subfields of the hippocampus peaked 2 hours after ECS and then returned to control levels by 24 hours after ECS. Silent mating-type information regulation 2 homolog 1 immunoreactivity levels in the dentate gyrus of hippocampus, hypothalamic paraventricular, dorsomedial, arcuate, and suprachiasmatic nuclei peaked 8 hours after ECS but had not completely returned to baseline levels 48 hours after ECS, except for the dentate gyrus. Electroconvulsive shock resulted in a gradual increase of SIRT1 immunoreactivity in the hypothalamic ventromedial nucleus and lateral hypothalamic area, which appeared to be still rising or peaking at the 48-hour post-ECS time point. The present results demonstrate that a single ECS increases SIRT1 in the mouse hippocampus and hypothalamus differentially in a region-specific time-dependent manner.

Disruption of component processes of spatial working memory by electroconvulsive shock but not magnetic seizure therapy

Self-ordered spatial working memory measures provide important information regarding underlying cognitive strategies, such as stereotypy. This strategy is based on repetitive sequential selection of a spatial pattern once a correct sequence has been identified. We previously reported that electroconvulsive shock (ECS) but not magnetic seizure therapy (MST) impaired performance on a spatial working memory task in a preclinical model. Here we tested the hypothesis that ECS disrupted stereotyped patterns in the selection of spatial stimuli. In a within-subject study design, we assessed the effects of ECS, MST, and sham on stereotypy and reaction time in a preclinical model. Stereotypy was assessed by the correlation of actual and predicted response patterns of spatial stimuli. Predicted patterns were based on performance during baseline sessions. ECS resulted in lower correlations between predicted and actual responses to spatial stimuli in two of the three subjects, and it also disrupted stereotypy. For one subject, there was change in the predictability of the spatial locus of responses between experimental conditions. For all three subjects, reaction time was significantly longer in ECS, relative to MST and sham. This is the first study to examine the effect of ECS, and to contrast the effects of ECS and MST, on spatial working memory component processes. Our preliminary findings show that ECS, but not MST decreased stereotypy and increased reaction time. This line of investigation may have significant implications in our understanding cognitive component processes of memory function and impairment.

Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain.

Réus GZ, Stringari RB, Rezin GT, Pezente DP, Scaini G, Maggi DD, De-Nês BT, Streck EL, Quevedo J, Feier G. Effects of maintenance electroshock on mitochondrial respiratory chain and creatine kinase activities in the rat brain.Objective:Electroconvulsive therapy is used efficacious treatment for a variety of complicated psychiatric disorders and evidences have indicated that energy metabolism impairment may be involved in pathophysiology and treatment of mood disorders. This work was performed to determine creatine kinase and mitochondrial respiratory chain activities at different times after the maintenance electroconvulsive shock (ECS).Methods:Male Wistar rats received a protocol mimicking therapeutic of maintenance or simulated ECS (sham) and were subsequently sacrificed immediately after, 48 h and 7 days after the last maintenance ECS. We measured creatine kinase and mitochondrial respiratory chain activities in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum.Results:Our results showed that maintenance ECS alter respiratory chain complexes and creatine kinase activities in the rat brain, but these effects were related to brain area and time after the ECS, in which the animal were killed.Conclusion:Finally, these findings further support the hypothesis that alteration on the energy metabolism could be involved in the therapeutic or adverse effects of ECS.

Effect of electroconvulsive shock on the glutamate level and the hyperphosphorylation of protein tau in depression rat models whose olfactory bulbs were removed.

To explore the effect of the electroconvulsive shock (ECS) on the glutamate level and the hyperphosphorylation of tau protein in depressed rats. The depression rat models whose olfactory bulbs were removed were established. Using the analysis of variance of factorial design, we set up two intervention factors including electric current (three levels: 25, 50, and 75 mA) and duration (three levels: 3, 6, and 9 times), which constituted 9 combinations (n=6). Fifty-four adult depression rat models whose olfactory bulbs were removed were randomly divided into nine experimental groups (n=6 in each group). The hippocampus was removed within 12 hours after the ECS finished. The level of glutamate in the hippocampus was detected by high-performance liquid chromatography, and that of Tau protein, which includes p-PHF-1(Ser396/404), p-AT8(Ser199/202), and p-12E8(Ser262), in the hippocampus with Western blot analysis. The glutamate level and the hyperphosphorylation of tau protein in the hippocampus of depressed rats remarkably increased. The changes of the hyperphosphorylation of tau protein were correlated with the electric current and duration of ECS, and these two factors showed an synergic effect. ECS enhances the hyperphosphorylation of tau protein in the hippocampus of depressed rats by up-regulating the glutamate level.

Tamalin Is a Critical Mediator of Electroconvulsive Shock-Induced Adult Neuroplasticity

The molecular mechanisms underlying the effects of electroconvulsive shock (ECS) therapy, a fast-acting and very effective antidepressant therapy, are poorly understood. Changes related to neuroplasticity, including enhanced adult hippocampal neurogenesis and neuronal arborization, are believed to play an important role in mediating the effects of ECS. Here we show a dynamic upregulation of the scaffold protein tamalin, selectively in the hippocampus of animals subjected to ECS. Interestingly, this gene upregulation is functionally significant because tamalin deletion in mice abrogated ECS-induced neurogenesis in the adult mouse hippocampus. Furthermore, loss of tamalin blunts mossy fiber sprouting and dendritic arborization caused by ECS. These data suggest an essential role for tamalin in ECS-induced adult neuroplasticity and provide new insight into the pathways that are involved in mediating ECS effects.

Effects of the noradrenergic neurotoxin DSP-4 on the expression of α1-adrenoceptor subtypes after antidepressant treatment

AbstractWe have previously reported that chronic imipramine and electroconvulsive treatments increase the α1A-adrenoceptor (but not the α1B subtype) mRNA level and the receptor density in the rat cerebral cortex. Furthermore, we have also shown that chronic treatment with citalopram does not affect the expression of either the α1A- or the α1B-adrenoceptor, indicating that the previously observed up-regulation of α1A-adrenoceptor may depend on the noradrenergic component of the pharmacological mechanism of action of these antidepressants. Here, we report that previous noradrenergic depletion with DSP-4 (50mg/kg) (a neurotoxin selective for the noradrenergic nerve terminals) significantly attenuated the increase of α1A-adrenoceptor mRNA induced by a 14-day treatment with imipramine (IMI, 20mg/kg, ip) and abolished the effect of electroconvulsive shock (ECS, 150mA, 0.5s) in the prefrontal cortex of the rat brain. The changes in the receptor protein expression (as reflected by its density) that were induced by IMI and ECS treatments were differently modulated by DSP-4 lesioning, and only the ECS-induced increase in α1A-adrenoceptor level was abolished. This study provides further evidence corroborating our initial hypothesis that the noradrenergic component of the action of antidepressant agents plays an essential role in the modulation of α1A-adrenoceptor in the rat cerebral cortex.