Hippocampus Of Depressed Rats Research Articles

Levomilnacipran Improves Lipopolysaccharide-Induced Dysregulation of Synaptic Plasticity and Depression-Like Behaviors via Activating BDNF/TrkB Mediated PI3K/Akt/mTOR Signaling Pathway.

Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression.

Retracted: Effects of miR-124-3p Silencing on Neuronal Damage in the Hippocampus of Depression Rats by Regulating STAT3 Gene

Retracted: Effects of miR-124-3p Silencing on Neuronal Damage in the Hippocampus of Depression Rats by Regulating STAT3 Gene

Metabolomics-based alleviation of depression by Xiaoyaosan through regulation of XDH and GRIA2

BackgroundXiaoyaosan is gradually gaining acceptance and recognition within the international scientific community. However, it still lacks appropriate methodological and theoretical descriptions that adhere to modern scientific standards. The development of omics technologies, particularly metabolomics, has facilitated the characterization of body physiology and can be used to guide clinical intervention. Aim of this studyThis study explored the therapeutic mechanism of Xiaoyaosan from a metabolomics perspective. MethodsWe recruited a total of 30 patients with mild to moderate depression and 15 healthy individuals, and collected urine samples from these participants for non-targeted metabolomics analysis. To establish a depressed rat model, we used chronic unpredictable mild stress in combination with orphan, and collected urine samples from the depressed rats for untargeted metabolomics analysis. Differential metabolites (DMs) were analyzed using multivariate data methods, and the biological pathways of DMs were analyzed using MetaboAnalyst 5.0. We comprehensively analyzed the urine metabolic fingerprints of depressed patients and rats to explore common characteristics of metabolic pathways and markers. We also analyzed the key targets of Xiaoyaosan in the treatment of depression and compared them to the targets of metabolic biomarkers. Finally, we verified the regulatory effects of Xiaoyaosan on key targets using real-time quantitative PCR and Western blot. ResultsIn the treatment of depression patients with Xiaoyaosan, we identified 243 DMs and 22 metabolic pathways. For depressed rats treated with Xiaoyaosan, we found 44 DMs and 9 metabolic pathways. Our comprehensive analysis of the urinary metabolic fingerprint revealed 7 important biological pathways and 6 crucial metabolic markers in the treatment of depression with Xiaoyaosan. The key targets of Xiaoyaosan in the treatment of depression were identified as XDH and GRIA2. Real-time quantitative PCR results demonstrated that Xiaoyaosan upregulated XDH expression in the brain's prefrontal cortex and GRIA2 expression in the brain's prefrontal cortex and hippocampus of depressed rats. Western blot results indicated that Xiaoyaosan upregulated XDH expression in the hypothalamus, prefrontal cortex, and hippocampus, as well as GRIA2 expression in the prefrontal cortex and hippocampus of depressed rats. ConclusionsOur study demonstrated that Xiaoyaosan regulates the metabolic disorders of depression and plays an antidepressant role through regulation of the expression of XDH and GRIA2 in the brain tissues of CUMS rats.

Opposing manner of miR-455-3p against NR2B-PSD-95-nNOS complex in the cortex and hippocampus of depressive rats under simulated complex space environment.

Depression in astronauts is one of the consequences of space flight effects, negatively impacting their work performances. Unfortunately, the underlying molecular mechanisms in space flight-induced depression are still unknown; however, various neuropsychiatric disorders reported that overexpressed NR2B-PSD-95-nNOS complex in the brain triggers various pathological pathways, and inhibiting NR2B-PSD-95-nNOS complex asserts antidepressant effects. Through our in silico analysis, we found that epigenetic regulator miR-445-3p targets PSD-95 and is hypothesized to down-regulate NR2B-PSD-95-nNOS complex to prevent neuronal damage associated with depression. Therefore, the present study is aimed to determine the novel insight of the miR-455-3p against the NR2B-PSD-95-nNOS complex in the neurobiology of space flight-induced depressive behavior. Using a simulated space environment complex model (SCSE) for 21 days, we induced depressive behavior in rats to analyze miR-455-3p expression and NR2B-PSD-95-nNOS complex in the cortex and hippocampus of the SCSE depressed rats through qRT-PCR and western blot analysis. Further, an in vitro microgravity model using rat hippocampus cell lines (RHNC) was utilized to identify the independent role of miR-455-3p on (1) NR2B-PSD-95-nNOS complex and TrKB-BDNF proteins, (2) oxidative stress, (3) nitric oxide level, (4) inflammatory cytokines, (5) mitochondrial biogenesis/ dynamics, and (6) cell survival. Our results showed that miR-455-3p regulates NR2B-PSD-95-nNOS complex in the SCSE depressed rats in opposite ways, with the cortex revealing a higher level of miR-455-3p and low-level NR2B-PSD-95-nNOS complex and the hippocampus showing down-regulated miR-455-3p and up-regulated NR2B-PSD-95-nNOS complex, indicating a region-specific change in the miR-455-3p and NR2B-PSD-95-nNOS complex in the SCSE depressed rats. Further RHNC results also confirmed down-regulated miR-455-3p and up-regulated NR2B-PSD-95-nNOS complex expression, similar to the findings in the hippocampus of SCSE rats, suggesting that microgravity influences miR-455-3p and associated changes. Additional investigations revealed that miR-455-3p targets PSD-95 and co-regulates NR2B-PSD-95-nNOS complex along with TrkB-BDNF signaling and exert protective effects against NR2B-PSD-95-nNOS complex, oxidative stress, nitric oxide, inflammatory cytokines, and mitochondrial defects, suggesting a valuable biomarker for devising depressive disorders.

New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway

ObjectiveTo clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling. MethodsTranscriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis. ResultsTranscriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway. ConclusionTaken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.

Effects of miR-124-3p Silencing on Neuronal Damage in the Hippocampus of Depression Rats by Regulating STAT3 Gene.

Objective A large amount of evidence shows that the abnormal expression of miRNA plays an important role in the development of depression. Therefore, we investigated the effect of miR-124-3p on neuronal damage in the hippocampus of depression rats. Methods The target genes of miR-124-3p were predicted by the database; the depression model was prepared by subcutaneous injection of corticosterone (CORT), and LV-miR-124-3p asponge lentiviral suspension was given to determine the weight of rats and open-field test, sugar preference experiment, Serum CORT, 5-HT, DA, and NE were measured, observe and record the behavior of rats, including behavior, diet, and hair. The expression of miR-124-3p, STAT3, Bcl-2, and Bax in rat hippocampus was measured. The rat hippocampal neuron cells were extracted and transfected with miR-124-3p inhibitor; the cells were cultured with CORT, and the cell survival rate was evaluated by MTT experiment, and the expressions of miR-124-3p, STAT3, Bcl-2, and Bax in the cells were detected. Luciferase reporter gene verifies the targeted regulation of miR-124-3p on STAT3. Results Compared with depression rats, silencing miR-124-3p increased the weight of the rats, increased the number of open-field activities, and significantly improved the general state and pathological state of the rats. The sugar water preference rate was significantly increased, the CORT content in the serum of rats decreased significantly, and the levels of 5-HT, DA, and NE increased significantly. After the treatment of silencing miR-124-3p, the expression level of miR-124-3p was decreased, while the STAT3 mRNA and protein expression levels were increased. And the protein and mRNA expression levels of Bcl-2 were increased, and the Bax protein and mRNA expression were decreased. Cell experiments verified that silencing miR-124-3p increased cell survival, the expression level of miR-124-3p decreased remarkably, while the expression levels of STAT3 mRNA and protein increased significantly. Silencing miR-124-3p reversed the effects of CORT treatment on miR-124-3p and STAT3 in neuronal cells. The luciferase reporter gene experiment confirmed that miR-124-3p targets and regulates STAT3 expression. Conclusion Silencing miR-124-3p may protect hippocampal neurons from damage in depression rats by upregulating STAT3 gene.

Xiaoyaosan Alleviates Hippocampal Glutamate-Induced Toxicity in the CUMS Rats via NR2B and PI3K/Akt Signaling Pathway.

Purpose: It is revealed that Xiaoyaosan could reduce glutamate level in the hippocampus of depressed rats, whose metabolism leads to the pathophysiology of depression. However, the underlying mechanism remains unclear. This study aims to explore the effect of Xiaoyaosan on glutamate metabolism, and how to regulate the excitatory injury caused by glutamate. Methods: Rats were induced by chronic unpredictable mild stress, then divided into control, vehicle (distilled water), Xiaoyaosan, fluoxetine, vehicle (DMSO), Xiaoyaosan + Ly294002 and Ly294002 groups. Ly294002 was microinjected into the lateral ventricular catheterization at 5 mM. Xiaoyaosan (2.224 g/kg) and fluoxetine (2.0 mg/kg) were orally administered for three weeks. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to assess depressive behavior. The glutamate and corticosterone (CORT) levels were detected by ELISA. Western blot, immunochemistry or immunofluorescence were used to detect the expressions of NR2B, MAP2, PI3K and P-AKT/Akt in the hippocampal CA1 region. The mRNA level of MAP2, NR2B and PI3K were detected by RT-qPCR. Results: Compared to the rats in control group, body weight and food intake of CUMS rats was decreased. CUMS rats also showed depression-like behavior as well as down regulate the NR2B and PI3K/Akt signaling pathway. Xiaoyaosan treatments could increase food intake and body weight as well as improved time spent in the central area, total distance traveled in the OFT. Xiaoyaosan could also decrease the immobility time as well as increase the sucrose preference in SPT. Moreover, xiaoyaosan decreased the level of glutamate in the hippocampal CA1 region and serum CORT in CUMS rats. Furthermore, xiaoyaosan improved the expression of MAP2 as well as increased the expression of NR2B, PI3K and the P-AKT/AKT ratio in the hippocampal CA1 region in the CUMS rats. Conclusion: Xiaoyaosan treatment can exert the antidepressant effect by rescuing hippocampal neurons loss induced by the glutamate-mediated excitotoxicity in CUMS rats. The underlying pathway maybe through NR2B and PI3K/Akt signaling pathways. These results may suggest the potential of Xiaoyaosan in preventing the development of depression.

The Spreading Depression Propagation: How Electrochemical Patterns Distort or Create Perception

At the transition from quiescence to propagating waves recorded in isolated retinas, a circular electric current closes in the extracellular matrix; this circular current creates a magnetic torus flow that, when entering quiescent tissue in front of the wave, recruits elements and when leaving behind, helps to build the absolute refractory state. The waving magnetic torus is the consequence of the vortex effect and explains the energy boost that drives propagation. Methods: We interpret experimental results from intrinsic and extrinsic fluorescence dyes, voltage, calcium and pH sensitive, optical signals from isolated retinas, and time series recordings using ion exchange resins: Ca, K, pH, Na, Cl recorded extracellularly at retinas, cerebellums and cortices coupled to spreading depression waves. Finally, we checked the ECoG activity, also a time series, at the transition from after discharges to spreading depression in rat hippocampus. Results: The integrated assessment of the diversified measurements led to the realization that the magnetic flow at the wavefront is a major contributor to the wave propagation mechanisms. This flow couples mass and charge flows as a swirling torus from excited to quiescent tissue. Conclusions: An alternative model of the brain is possible, apart from the classical HH and molecular biology model. Physical chemistry of charged gels and its flows explains the results. The conceptual framework uses far from equilibrium thermodynamics.

Long non-coding RNA uc.80- overexpression promotes M2 polarization of microglias to ameliorate depression in rats.

Microglia polarization is associated with the pathogenesis of depression. A previous study shows that long non-coding RNA uc.80- is down-regulated in the hippocampus of depressed rats. Thus, this article aims to investigate the role of uc.80- in microglia polarization in depression. We first established depression model rats by chronic unpredictable mild stress (CUMS) regiment. We found that hippocampus of depressed rats exhibited an increase of M1 microglias and a decrease of M2 microglias. uc.80- was down-regulated in hippocampus of depressed rats. Furthermore, the detection of behaviouristics of depressed rats showed that uc.80- overexpression alleviated depression of rats. In addition, uc.80- overexpression promoted M2 polarization of microglias in vivo and in vitro. uc.80- overexpression led to a decrease in apoptosis of hippocampal neurons in vivo and in vitro. In conclusion, our study confirms that lncRNA uc.80- overexpression ameliorates depression in rats by promoting M2 polarization of microglias. Thus, our work suggests that uc.80- may be a target gene for depression treatment.

Effects of Vortioxetine on depression model rats and expression of BDNF and Trk B in hippocampus.

Effects of Vortioxetine on the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (Trk B) in hippocampus of depressive rats were investigated. Forty-five SD rats were randomly divided into three groups: model control, Vortioxetine and normal control group, with 15 rats in each group. The changes of body mass were recorded within 5 weeks, and the open field test, sugar water preference test and Morris water maze test were performed to evaluate the behavior and mental status of the rats. The expression of BDNF and Trk B in rat hippocampus was detected by enzyme-linked immuno sorbent assay. Compared with the model control group, the body mass, horizontal and vertical movement, sugar and water preference rate of the vortioxetine group in the 5th week were significantly higher than those of the model control group (P<0.05), and significantly lower than those of the normal control group (P<0.05). The escape latency of the Vortioxetine group within 4 days was significantly lower than that of model control group (P<0.05), but higher than that of normal control group (P<0.05). The target quadrant residence time of the Vortioxetine group was significantly lower than that of the model control group (P<0.05), but higher than that of the normal control group (P<0.05). Expression of BDNF and Trk B in the Vortioxetine group was significantly higher than that in the model control group (P<0.05), but lower than that of the normal control group (P<0.05). Collectively, Vortioxetine can effectively alleviate the symptoms of autonomous and exploratory behavior, and reduce the decrease of learning and memory in depressive rats. Vortioxetine can increase the expression of BDNF and Trk B in depressive rats and alleviate their depressive behavior.

Si-Ni-San Prevents Reserpine-Induced Depression by Inhibiting Inflammation and Regulating CYP450 Enzymatic Activity.

Depression is becoming a major public health concern worldwide. Si-Ni-San (SNS) is a famous formula in Traditional Chinese Medicine (TCM) with potent antidepressant effects. However, the antidepressant mechanism of SNS has not been clearly elucidated. This study was performed to verify whether the antidepressant effects of SNS were related to its anti-inflammatory effects, the levels of brain-derived neurotrophic factor (BDNF) and Cytochrome P450 (CYP450) enzymatic activity. In our study, behavioral tests such as the forced swim test, sucrose preference test and open-field test were evaluated to ensure the establishment of depressive rats. The levels of IL-1β, IL-6, and TNF-α in the serum, liver, and hippocampus of rats were measured by enzyme-linked immunosorbent assays (ELISA). Furthermore, the key proteins NF-κB, BDNF, and TrkB were analyzed by Western blot (WB) analysis in the hippocampus. In addition, CYP450 enzymatic activity analysis was performed using LC-MS/MS in conjunction with drug and statistics (DAS 3.0) after oral administration of six probe drugs. Our results showed that SNS attenuated reserpine-induced increases in IL-1β, IL-6, and TNF-α expression in the serum, liver, and hippocampus. The levels of NF-κB, BDNF, and TrkB in the hippocampus of depressive rats were also altered. According to the pharmacokinetic parameters, SNS had moderate inhibitory effects in the reserpine-induced depression model on CYP1A2, CYP2D1, CYP2E1, and CYP3A2, but no significant metabolic changes to CYP2C6 and CYP2D2. These findings suggested that SNS has a protective effect on reserpine-induced depressive rats, which may be related to the improvement of the inflammatory factors, the level of BDNF and the activity of CYP450 enzymes.

Effect of Electroacupuncture on Reuptake of Serotonin via miRNA-16 Expression in a Rat Model of Depression.

The current study aimed to investigate the effects and mechanisms of electroacupuncture (EA) treatment applied to Bai hui (GV20) and Yin tang (GV29) acupoints (1 mA, 2 Hz, continuous wave, 20 minutes) for 28 days in a rat model of chronic unpredictable mild stress (CUMS) on reuptake of serotonin (5-hydroxytryptamine (5-HT)) and miRNA-16 levels in the hippocampus and serum. Rats were housed in individual cages, and CUMS was used to establish a rat model of depression. After EA treatment for 4 weeks, behavioral changes and indices including 5-HT transporter (SERT), 5-HT, and miRNA-16 levels in the hippocampus and serum were examined. The EA treatment significantly improved base levels of sucrose preference and exploratory behavior and significantly decreased SERT protein and mRNA expression in the hippocampus of depressed rats. Significantly increased 5-HT levels were observed, and miRNA-16 levels were significantly decreased in the hippocampus and serum of depressed rats. In conclusion, the antidepressant effects of EA treatment may be affected via inhibition of 5-HT reuptake, upregulation of 5-HT levels, and inhibition of miRNA-16 expression in the hippocampus and serum.

ITRAQ-Based Protein Profiling in CUMS Rats Provides Insights into Hippocampal Ribosome Lesion and Ras Protein Changes Underlying Synaptic Plasticity in Depression.

Hippocampal atrophy is one of the key changes in the brain implicated in the biology of depression. However, the precise molecular mechanism remains poorly understood due to a lack of biomarkers. In this research, we used behavioral experiments to evaluate anxiety and anhedonia levels in depressed rats using chronic unpredictable mild stress (CUMS) modeling. We also used isobaric tag for relative and absolute quantitation (iTRAQ) to identify the differentially expressed hippocampal proteins between depressed and normal rats. Bioinformatics analyses were also performed for a better understanding. The results showed that CUMS rats had higher anxiety and anhedonia levels than control rats, along with hippocampal lesions. Through iTRAQ and bioinformatics analyses, we found that ribosome proteins were significantly downregulated and Ras proteins exhibited a mixed change in the hippocampus of depressed rats. These findings suggest that the expression of hippocampal ribosome lesions and Ras proteins is significantly different in depressed rats than in control rats, providing new insights into the neurobiology of depression.

Antidepressant mechanisms of venlafaxine involving increasing histone acetylation and modulating tyrosine hydroxylase and tryptophan hydroxylase expression in hippocampus of depressive rats.

Venlafaxine (VEN) is a widely used antidepressant as a serotonin-reuptake and norepinephrine-reuptake inhibitor. It is used primarily in depression, especially with generalized anxiety disorder or chronic pain. This medicine is of interest because its mechanisms involved multiple aspects. In the current study, the antidepressant action of VEN was investigated by studying the histone acetylation and expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in rats exposed to chronic unpredicted stress (CUS) for 28 days. Male Sprague-Dawley rats were divided into a control group, VEN-treated control group, CUS group, and VEN-treated CUS group. VEN (23.4 mg/kg once daily) was administered to rats by intragastric gavage, whereas the same volume of vehicle was given to rats in the control and model groups. Rat behaviors, acetylated H3 at lysine 9 (acH3K9), acetylated H3 at lysine 14 (acH3K14), acetylated H4 at lysine 12 (acH4K12), histone deacetylase 5, and TH and TPH expression in the hippocampus were determined. Chronic VEN treatment significantly relieved the anxiety- and depression-like behaviors, prevented the increase of histone deacetylase 5 expression and decrease of acH3K9 level, and promoted TH and TPH protein expression in the hippocampus of CUS rats. The results suggest that the preventive antidepressant mechanism of VEN is partly involved in the blocking effects on histone de-acetylated modification and then increasing TH, TPH expression.

Effect of fluoxetine on the expression of angiogenic factors in hippocampus of depressive rats

Objective Effect of fluoxetine on the expression of angiogenic factors in hippocampus of depressive rats. Methods 32 male SD rats (3 month) of SPF level were randomly divided into fluoxetine group (n=8), fluoxetine + LY294002 intervention group (n=8), model group (n=8) and control group (n=8). Control group without any treatment was free to eat and water for 5 weeks.The rats in the other groups were modeled by chronic, mild and unpredictable multiphase stress.The fluoxetine group was treated with fluoxetine for 2 weeks after modeling, and the intervention group was given LY294002 intervention, then the fluoxetine treatment for 2 weeks, the model group was free to eat and drink for 2 weeks.At the end of the 5th week, all the rats were decapitated and the hippocampus was removed on the ice bath.Western blot was performed to detect the expression of angiogenic factors. Results Compared with the model group (vascular endothelial growth factor(VEGF)(0.44±0.08), fetal liver kinase 1(FLK1)(0.37±0.15), protein kinase B1( AKT1)(0.40±0.10), p-AKT1(0.53±0.07)), the expression of VEGF(0.98±0.13), FLK1(1.09±0.21), AKT1 (1.05±0.05) and p-AKT1 (1.01±0.13)in hippocampus of fluoxetine group were significantly increased, and the differences were statistically significant (P<0.01). And the expression of VEGT, FLK1, p-AKT1 in fluoxetine group increased compared with those of fluoxetine + LY294002 intervention group (VEGF (0.55±0.08), FLK1 (0.55±0.14) and p-AKT1(0.60±0.05)), and the difference were statistically significant (P<0.01). Conclusion Fluoxetine can increase the expression of VEGF/FLK1 and p-AKT1 proteins in the hippocampus of depressed rats, which in turn may be involved in the regeneration of hippocampal blood vessels.This effect of fluoxetine may be related to the PI3K/AKT signaling pathway. Key words: Depression; Hippocampus; Angiogenic factors; Rat; PI3K/AKT signaling pathway; VEGF /FLK1; AKT1/p-AKT1

Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

Alcohol (ethanol) disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA) neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature.

Abnormal levels of seven amino neurotransmitters in depressed rat brain and determination by HPLC-FLD.

The determination of amino acids with actions like neurotransmitters or modulators has been increasingly important for diagnosis in many neuropsychiatric diseases. A rapid and simple high-performance liquid chromatography with fluorescence detection method was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ-aminobutyric` acid (GABA). Homoserine was used as an internal standard. The analysis was performed on a BDS column with methanol and 50 mm sodium acetate solution (pH 6.5) using a simple gradient elution. Several parameters of the developed method were validated including linearity, accuracy, precision, extraction recovery and stability, which were within the acceptable range. The method was successfully applied to determination of real samples: hippocampus and cortex in depressed rats exposed to chronically unpredictable stress in order to study if there existed differences in the seven amino acids levels between depressed rats and control. The results showed that Asp, Gly, Tau and GABA significantly decreased with increasing Gln in the hippocampus of depressed rats, compared with that of the control group, among which obviously lower level of Asp and higher level of Gln in cortex were observed. The analytical method and the results could be useful for clinical diagnosis and further insight into pathophysiological mechanism of depression.

Electroacupuncture Restores 5-HT System Deficit in Chronic Mild Stress-Induced Depressed Rats.

Objective. The current study is designed to investigate the antidepressant efficacy of electroacupuncture (EA) treatment by evaluating its effect on the synthesis, metabolism, reuptake, and receptors of 5-hydroxytryptamine (5-HT), so as to clarify the molecular mechanisms of EA for antidepression. Materials and Methods. Solitary combined with the chronic unpredictable mild stress (CUMS) was used to establish the rat model with depression. The depressed rats were supplied with EA treatment for 4 weeks, and the behavior change and the following indices including 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), monoamine oxidase A (MAO-A), tryptophan hydroxylase (TPH), 5-HT transporter (SERT), 5-HT1A, and 5-HT2A in hippocampus and prefrontal cortex were examined. Results. EA treatment significantly improved the behavior of rats and increased 5-HT level in hippocampus of depressed rats. Similarly, EA treatment could significantly increase protein and mRNA expression of TPH and 5-HT1A during 5-HT synthesis process in hippocampus of depressed rats. However, EA treatment had no effect on the activity of MAO-A and the expression of SERT protein and mRNA. Conclusion. Antidepressant efficacy of EA treatment can be accomplished through enhancing 5-HT synthesis, upregulating 5-HT1A level, and improving 5-HT content in brain and synaptic gaps.

Propofol can Protect Against the Impairment of Learning-memory Induced by Electroconvulsive Shock via Tau Protein Hyperphosphorylation in Depressed Rats.

To explore the possible neurophysiologic mechanisms of propofol and N-methyl-D- aspartate (NMDA) receptor antagonist against learning-memory impairment of depressed rats without olfactory bulbs. Models of depressed rats without olfactory bulbs were established. For the factorial design in analysis of variance, two intervention factors were included: electroconvulsive shock groups (with and without a course of electroconvulsive shock) and drug intervention groups [intraperotoneal (ip) injection of saline, NMDA receptor antagonist MK-801 and propofol. A total of 60 adult depressed rats without olfactory bulbs were randomly divided into 6 experimental groups (n=10 per group): ip injection of 5 ml saline; ip injection of 5 ml of 10 mg/kg MK-801; ip injection of 5 ml of 10 mg/kg MK-801 and a course of electroconvulsive shock; ip injection of 5 ml of 200 mg/kg propofol; ip injection of 5 ml of 200 mg/kg propofol and a course of electroconvulsive shock; and ip injection of 5 ml saline and a course of electroconvulsive shock. The learning-memory abilities of the rats was evaluated by the Morris water maze test. The content of glutamic acid in the hippocampus was detected by high-performance liquid chromatography. The expressions of p-AT8Ser202 in the hippocampus were determined by Western blot analysis. Propofol, MK-801 or electroconvulsive shock alone induced learning-memory impairment in depressed rats, as proven by extended evasive latency time and shortened space probe time. Glutamic acid content in the hippocampus of depressed rats was significantly up-regulated by electroconvulsive shock and down-regulated by propofol, but MK-801 had no significant effect on glutamic acid content. Levels of phosphorylated Tau protein p-AT8Ser202 in the hippocampus was up-regulated by electroconvulsive shock but was reduced by propofol and MK-801 alone. Propofol prevented learning-memory impairment and reduced glutamic acid content and p-AT8Ser202 levels induced by electroconvulsive shock. Electroconvulsive shock might reduce learning-memory impairment caused by protein Tau hyperphosphorylation in depressed rats by down-regulating glutamate content.

The possible relationship between expressions of TRPC3/5 channels and cognitive changes in rat model of chronic unpredictable stress

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel dominantly permeable to Ca2+. It consists of seven homologues, TRPC1–TRPC7, based on their sequence similarity. According to some researches, the expression of TRPC3/5 in hippocampus is related to the morphological changes of hippocampus, including axon length and dendritic spine density [1]. This study observed whether the expression of TRPC3/5 was changed in chronic unpredictable stress (CUS)-induced depression of rat model and can the altered TRPC3/5 expression affect the morphology of neurons in hippocampus of depressive rats as well as the cognitive ability. A total of 16 rats were equally and randomly divided into two groups: the control group and the depression model group, which underwent a process of CUS for three weeks. Western blot assay was conducted to test the content of TRPC3/5 in hippocampus, and Golgi-Cox staining was used to observe the morphological changes of neurons in hippocampus. Morris water maze (MWM) test was performed to observe the changes of spatial cognitive ability of rats while the long-term potentiation was applied to evaluate synaptic plasticity. Results showed that there was a difference in the expression of TRPC3/5 in hippocampal neurons, as well as the neuron morphology between control group and depression model group. At the same time the cognitive ability and synaptic plasticity were significantly changed. Results suggest that there is an association between expressions of TRPC3/5 and cognitive changes in CUS rat model, and the mechanism maybe that the different expressions of TRPC3/5 can cause morphological changes of the neurons in hippocampus, which has a profound impact on the spatial cognitive ability and synaptic plasticity.