Open-field Test Scores Research Articles

Downstream passage performance of silver eel at an angled rack: effects of behavior and morphology

The European eel is critically endangered due to heavy impact of anthropogenic factors, such as habitat fragmentation, overexploitation and climate change. During downstream migration, silver eels may encounter hydropower plants, which often result in delay or mortality from impingement on trash-racks or turbine passage. These problems can be mitigated with downstream passage solutions, such as angled racks that guide downstream-migrating eels to safe passage routes. The importance of bar spacing and phenotypic diversity for passage performance is, however, largely unknown. In this study, we investigated how morphological parameters (body mass, eye and fin indices) and behavioral score (open field test) influenced passage rate at an experimental intake equipped with a bypass and angled racks with either 15 or 30 mm bar spacing. Both racks were efficient in guiding eels into a bypass. There was a strong positive effect of body mass and a weak positive effect of open field test score on passage rate. Other factors such as eye and fin indices played a minor role. These results demonstrate the performance of angled racks with bypasses and form a useful starting point for further research regarding the relationships between individual variation in behavior, morphology and passage solutions for silver eels.

Study on the Mechanism of Hydrolyzed Seawater Pearl Tablet in Treating Chronic Sleep Deprivation Mice Model.

Modern lifestyle increasingly deprives people from sleep to different degrees. Long-term sleep deprivation will facilitate body's pathological behaviors, such as lethargy, depression, and anorexia. This study is an investigation into the mechanism of hydrolyzed seawater pearl tablet in treating chronic sleep deprivation mice model. The chronic sleep deprivation model was established involving C57BL/6mice; the body weight, behavioral characteristics, hippocampal structure, oxidative stress, apoptosis-related protein expression, and intestinal bacteria in mice were assessed to characterise hydrolyzed seawater pearl tablet. Hydrolyzed seawater pearl tablet significantly accelerated body weight, open field test score, and sugar water preference rate (P < 0.05), alleviated the structural damage of hippocampus, reduced the content of MDA (P < 0.05), Bax protein expression, increased the content of GSH (P < 0.05), the activities of SOD, GSH-Px, and Bcl-2 protein expression in the hippocampus, increased the Escherichia coli, Bacteroides, Bifidobacterium and Lactobacillus (P < 0.05), which are beneficial bacteria in the intestine, in chronic sleep deprivation mice, and reduced the amount of Clostridium perfringens (P < 0.05), which are harmful bacteria in the intestine. Hydrolyzed seawater pearl tablet can improve the depression-like mental state of mice caused by chronic sleep deprivation. The mechanism involves improving the antioxidant activity of the hippocampus to eliminate the excessive ROS, which inhibits cell apoptosis and alleviates tissue structure damage. Meanwhile, it may also be involved in adjusting the microbiota level and improving the mental and behavioral activities of chronic sleep deprivation mice through the intestine-brain axis.

Apple phenolic extracts ameliorate lead-induced cognitive impairment and depression- and anxiety-like behavior in mice by abating oxidative stress, inflammation and apoptosis via the miR-22-3p/SIRT1 axis.

Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.

Lipocalin-2 Regulates Hippocampal Microglial Activation in Poststroke Depression.

Background and Purpose: Microglia play important role in poststroke depression (PSD), however, the exact mechanism was still unclear. The purpose of the study was to study the mechanism of microglial activation in PSD.Methods: 24 rats were randomly divided into three groups: the PSD group (n = 10), the poststroke (PS) group (n = 7), and the sham group (n = 7). Primary hippocampal microglia were isolated and cultured, and recombined LCN2 protein was used to stimulate the cultured microglia. The protein expression of Iba1, P38 MAPK and PP38 MAPK was analyzed by western blotting; the LCN2 expression was measured by RT-qPCR, the serum LCN2 level and the NO level were analyzed by ELISA.Results: Open field test scores (horizontal score, vertical score, and self-grooming score) and the serum LCN2 level were significantly decreased in the PSD group compared with the other two groups (P < 0.05). The serum LCN2 level was positively correlated with the horizontal score and negatively correlated with the self-grooming score in the open field test (P < 0.05). The relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the hippocampal region compared with other brain regions (P < 0.05), while the relative protein level of Iba1 and the LCN2 mRNA level were significantly increased in the PSD group compared with the other two groups (P < 0.05). The length, supernatant NO level, phagocytic ability and migration ability of LCN2-treated microglia were significantly increased compared with those of untreated microglia (P < 0.05). The relative protein levels of P38 MAPK and the PP38 MAPK significantly increased in hippocampal region in the PSD group and LCN2-treated hippocampal microglia (P < 0.05).Conclusion: Hippocampal microglia are activated during PSD; LCN2 may regulate hippocampal microglial activation by the P38 MAPK pathway in the process of PSD.

Behavioral and Biochemical Effects of KXS on Postmyocardial Infarction Depression.

BackgroundDepression and coronary heart disease (CHD) often occur together in clinical practice. As a traditional Chinese medicine, Kai-Xin-San (KXS) has been widely used for the treatment of emotion-related disorders. In the present study, we aimed to explore whether KXS had both antidepressive effects and cardioprotective functions in a rat model of myocardial ischemia (MI) with depression.MethodsA total of 50 SD rats were randomly assigned into five groups as follows: normal control (control group), celiac injection of isopropyl adrenaline (ISO) (MI group), depression (depression group), MI+ depression (model group) and MI+ depression treated with intragastric administration of 370 mg/kg KXS (KXS group). MI was induced by subcutaneous injection of 85 mg/kg ISO. Depression was developed by a 7-week chronic mild stress (CMS) challenge. Behavioral test was conducted before and during the experiment. Echocardiography and biochemical analysis were carried out after 7 weeks of CMS challenge.ResultsAfter 7 weeks of experiment, depression-like behaviors were observed in all the groups except for control and KXS groups, and KXS treatment dramatically increased open-field test scores and sucrose consumption (P < 0.01 vs. model group). Echocardiography and biochemical analysis showed that KXS treatment could improve levels of ejection fraction (EF) and fractional shortening (FS), which were reduced by depression and ISO challenge. Meanwhile, KXS treatment significantly decreased the levels of creation kinase MB (CK-MB) and lactate dehydrogenase (LDH), which were increased in the model group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) were increased, while the malondialdehyde (MDA) activity was significantly decreased in the KXS group. Moreover, KXS treatment reduced the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in myocardial tissue compared with the model group.ConclusionsKXS had antidepressant-like activity and offered cardioprotective effects against ISO-induced myocardial infarction with depression.

Preventive and curative effects of grape seed powder on stroke using in vitro and in vivo models of cerebral ischemia/reperfusion

Stroke is a worldwide concern. Many studies pointed out relevant preventive effect of grape seed powder (GSP) against deleterious brain ischemia/reperfusion (I/R) injury, but curative effect has been scarcely approached.The present work aimed at studying the preventive and curative effect of GSP against stroke using in-vitro and in-vivo models. Primary neuron-astrocyte cocultures were used to evaluate in-vitro GSP protective and curative effect on oxygen-glucose-deprivation (OGD). A murine I/R model, in which GSP was administered as delayed post stroke drug, to evaluate its potential clinically translatable therapy was used and behavioral tests were conducted after 15 days. Ultra-structure of hippocampus dentate gyrus using Transmission Electron Microscopy (TEM) was also undertaken.GSP prevented OGD-induced toxicity and cell death in a dose dependent manner and was neuroprotective as assessed by sustained cell viability (70 % ±1 for OGD + GSP and 37 % ±2 for OGD) and modulated cytokines and brain derived neurotrophic factor (BDNF) expression. GSP also promoted behavioral outcomes by increasing step-down inhibitory time from 17s±4 to 50s±11 and rat overall activities by improving scores in open field test to near control level. Furthermore, GSP protected hippocampus dentate gyrus area from I/R-induced drastic alterations as assessed by reduced autophagic vacuoles.

Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice.

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall improvement of patients with major depressive disorder (MDD). Therefore, the purpose of this study was to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and then evaluate the anti-depression effect of Xiaoyaosan. Mice were randomly divided into four groups: a control group, a model group, a treatment group with Xiaoyaosan, and a treatment group with fluoxetine. All mice were individually kept in cages, and depression was induced in the mice by exposing them to several designed manipulations of CUMS for 21 days, as described in the protocol. Mice in the control group and model group received 0.5 mL of distilled water, while mice in the treatment groups received either Xiaoyaosan (0.25 g/kg/day) or fluoxetine (2.6 mg/kg/day). The drugs used in the study were given intragastrically daily during the entire three weeks. To estimate the depressive-like behaviors, a series of parameters including the coat state, body weight, open field test score, and sucrose preference test score were recorded. Data analysis showed that behaviors of model mice were significantly changed compared to behaviors of mice in the control group, which were improved by the treatment of Xiaoyaosan and fluoxetine. The current findings demonstrated the anti-depression effects of Xiaoyaosan on the behaviors of CUMS-induced mice and revealed that compounds from the Xiaoyaosan prescription may be worthwhile for treating depression, considering their beneficial effects on depressive-like behaviors.

Ntf3 hypermethylation in antenatal PTSD and preventive effect of the Chinese herbal medicine Jin Kui Shen Qi Wan

ABSTRACTAntenatal post-traumatic stress disorder (PTSD can leave offspring with life-long mental and behavioural disorders. This study investigated the epigenetic mechanism of the effects of Jin Kui Shen Qi Wan (JKSQW) in preventing antenatal PTSD. Thirty-six pregnant rats were randomized into Control, PTSD and JKSQW. Offspring characteristics were investigated with open-field test (OFT), elevated pull maze (EPM), gene expression profile chip test and methylated DNA immunoprecipitation sequencing. In the OFT test, the PTSD offspring showed lower OFT scores than the Control and JKSQW groups (p < 0.05). The PTSD group's EPM performance, OE (open arm entry) + CE (closed arm entry), OE% and OT% (open arm time) were also lower than those of either the Control or the JKSQW group (p < 0.05). In the gene expression profile chip test, 54 genes showed dysregulation through PTSD intervention and were normalized by JKSQW. Endocytosis (Epn3, Folr1 and Hspa1l) and MAPK signaling (Fgf17, Hspa1l, Ntf3 and Pla2g5) pathways were annotated. Combining those genes and methylation sequencing, Ntf3 was identified in both tests. Compared with the Control, the PTSD offspring showed Ntf3 hypermethylation (Log2FC = 1.022) at 225679501∼225680000 on Chromosome 4 and downregulation in the gene expression profile. The Ntf3 methylation level in JKSQW was restored nearly to the Control level (Log2FC = −1.082 in JKSQW vs. PTSD). In conclusion, the reduction in the offspring's behavioural performance might constitute experimental evidence of kidney deficiency due to Ntf3 hypermethylation, which could be prevented by JKSQW.

MicroRNA-27a participates in the pathological process of depression in rats by regulating VEGFA.

The present study aimed to determine the expression of vascular endothelial growth factor A (VEGFA) and microRNA (miRNA/miR)-27a in hippocampal tissues, and serum from a depression model of rats. In addition, the present study aimed to understand the mechanism of regulation of miR-27a in depression. A total of 40 male rats were selected, and divided into the control and depression model groups. The rats in the model group were subjected to 14 types of stimulations to model depression. By determining the body weight, syrup consumption rate and open field test score, the extent of depression in the rats was evaluated. Quantitative-polymerase chain reaction was used to determine the expression of VEGFA mRNA and miR-27a in hippocampal tissues, and serum. ELISA was used to measure the content of VEGFA protein in serum, while western blotting was employed to determine the expression of VEGFA protein in hippocampal tissues. A dual luciferase assay was carried out to identify the interactions between VEGFA mRNA and miR-27a. The rats in the depression model group showed depression symptoms and the depression model was successfully constructed. Rats with depression had lower VEGFA mRNA and protein expression in the hippocampus, and peripheral blood compared with the control group. Rats in the depression model group had reduced levels of miR-27a in the hippocampus and peripheral blood, which may be associated with the levels of VEGFA. miR-27a was able to bind with the 3′-untranslated region of VEGFA mRNA to regulate its expression. The present study demonstrated that miR-27a expression in hippocampal tissues and blood from rats with depression is upregulated, while the expression of VEGFA mRNA and protein is downregulated. miR-27a may participate in the pathological process of depression in rats by regulating VEGFA.

Effects of Chailong Jieyu Pill on Behavior, Monoamine Neurotransmitters, and Corticosteroid Receptors in a Rat Model of Anxiety Disorder

Chailong Jieyu Pill (CJP) is composed of Radix Bupleuri, Radix Scutellariae, Rhizoma Pinelliae Preparata, Radix Codonopsis, Radix Glycyrrhizae preparata, keel, Concha Ostreae, Concha Margaritifera Usta, Rhizoma Zingiberis Recens, and Fructus Jujubae. CJP has shown good clinical effects on improving anxiety disorders. However, as the mechanism underlying such benefits remains unclear, the aim of this study was to investigate the mechanism of action for CJP on anxiety-related behaviors in a rat model of anxiety disorder. After establishing a rat model of anxiety disorder using uncertain empty bottle stimulation, rats were divided into control, model, citalopram, low-dose CJP, and high-dose CJP groups. After 1 month of administration, effects of treatments on rat appearance, body weight, and open-field test scores were observed. In addition, hippocampal monoamine neurotransmitter (5-hydroxytryptamine, dopamine, and norepinephrine) contents were measured with an enzyme-linked immunosorbent assay, and mRNA expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) were measured with reverse transcription-polymerase chain reaction. CJP increased rat weight, and this effect was increased in the high-dose CJP group compared with the citalopram group (P < 0.05). CJP also elevated open-field test scores compared with the citalopram group (P < 0.05). While CJP decreased monoamine neurotransmitter contents in rat hippocampus, the regulatory effect of CJP on 5-hydroxytryptamine was reduced compared with citalopram (P < 0.01). CJP upregulated GR mRNA expression in both low-dose (P < 0.05) and high-dose (P < 0.01) CJP groups, but only the latter significantly downregulated MR mRNA expression and showed enhanced effects compared with citalopram (P < 0.05). Thus, CJP likely exerted its significant antianxiety effect by diminishing monoamine neurotransmitters and regulating mRNA expression of MR and GR in the hippocampus of our rat model of anxiety disorder.

Effects of electroacupuncture on synaptic plasticity in hippocampal CA3 area of rats with chronic stress depression

To explore the effects of electroacupuncture (EA) on behavioral function and synaptic plasticity in hippocampal CA3 area in rats with chronic stress depression. According to the random number table method, 144 SD male rats were assigned into a blank group, a model group, an EA group and a fluoxetine group, then each group was divided into a 7 d subgroup, a 14 d subgroup and a 21 d subgroup, 12 rats in each subgroup. The chronic mild unpredictable stress stimulus combined with lonely breeding were applied to establish the depression model of rats, which was performed simultaneously with intervention treatment. The rats in the EA group were treated with EA (dilatational wave) at "Shenting" (GV 24) and "Baihui" (GV 20), while the rats in fluoxetine group were treated with intragastric administration of fluoxetine, once daily. With open-field test, sugar consumption experiment and transmission electron microscope, the changes of behavior and neuronal synapse inhippocampal CA3 area were observed. On 7 d, 14 d and 21 d, compared with the blank group, the open-field test score, sugar consumption and body mass were significantly lower in the model group (all P<0.01); compared with the model group, the open-field test score, sugar consumption and body mass were significantly higher in the EA group and the fluoxetine group on 14 d and 21 d (P<0.01, P<0.05). On 14 d and 21 d, compared with the blank group, the synapse in hippocampal CA3 area was significantly lower in the model group (both P<0.01); compared with the model group, the synapse in hippocampal CA3 area was significantly higher in the EA group and the fluoxetine group (P<0.01, P<0.05). The neurons cells in hippocampal CA3 area in the model group showed pyknosis and deformation from 7 d with fusion structure and unclear boundary of synapse, which were significantly improved on 21 d; the neurons cells in hippocampal CA3 area in the EA group and the fluoxetine group were significantly improved from 14 d and restored to normal level on 21 d, in addition, the structure of synapse restored to normal level. EA is involved in the regulation of synaptic plasticity in hippocampal CA3 area, and promotes the recovery of depression symptoms.

Abnormal Expression of MicroRNAs Induced by Chronic Unpredictable Mild Stress in Rat Hippocampal Tissues.

Previous research has demonstrated that the behaviors observed in chronic unpredictable mild stressed (CUMS) rats are similar to the symptoms of depressed patients and that the abnormal expression of cerebral microRNAs is associated with depressive disorder. However, little is known regarding the expression profile of microRNAs induced by CUMS. In this study, we aimed to examine the hippocampal microRNA expression profile in CUMS rats. Forty adolescent male Sprague-Dawley rats were randomly divided into normal and model groups. The rats in the model group were stimulated daily with randomly applied mild stressors from among 14 different mild stressors. The stressors were changed every day and were applied for 35 consecutive days. On the 28th and 35th days after treatment, the weights, physical condition, sucrose preference, and open-field test scores of the rats of the two groups were evaluated. Successful induction of CUMS was considered if the differences of the above metrics between the two groups were statistically significant on the 28th and 35th days after treatment. Cerebral sucrose metabolism images of rats were obtained by 18F-FDG PET/CT. The rats were euthanized under anesthesia, and hippocampal tissues were collected for hematoxylin-eosin (HE) staining. In addition, the samples were used for microRNA array chip and qRT-PCR analysis. The target genes of different microRNAs were predicted using bioinformatic analysis, and the functions and signal pathways of these target genes were investigated by GO and KEGG analyses. Sixteen rats exhibited successful induction of CUMS. Cerebral 18F-FDG PET/CT imaging showed that the glucose metabolism rate of CUMS rats were significantly lower than normal rats in the central nucleus of the inferior colliculus (CIC, p=0.022), the retrosplenial agranular area (RSA, p=0.002), the second sensory cortex (S2, p=0.028), the first auditory cortex (Au1, p=0.012), the primary somatosensory cortex, barrel field (SIBF, p=0.001), and the ventral posteromedial nucleus (VPM) of the right thalamus (p=0.048). HE staining showed that hippocampal pyramidal cells CUMS rats were thinner, disordered, and exhibited irregular shapes, with many pyknotic cells. The microarray chip and qRT-PCR analysis revealed that five microRNAs were significantly up-regulated [miR-382-3p (p=0.026), miR-183-5p (p=0.018), miR-3573-5p (p=0.042), miR-202-3p (p=0.016), miR-493-3p (p=0.009)], and only miR-370-3p was significantly down-regulated (p=0.036). miRNA target gene prediction and functional annotation analysis showed significant enrichment in several GO terms and pathways associated with depression. Our findings provide supportive evidence for the abnormal expression of multiple CUMS-induced hippocampal microRNAs in rats as well as the involvement of these microRNAs in depressive disorder.

Repetitive transcranial magnetic stimulation for treating depressive behavior in response to chronic but unpredictable mild stress

Objective To observe the effect of repetitive transcranial magnetic stimulation (rTMS) on behavior in response to chronic but unpredictable mild stress and explore potential neuroendocrine mechanisms. Methods Forty adult SD male rats were randomly divided into a control group (n=8) and a model preparation group (n=32). The control group was given normal care while a model of depression was induced in the model preparation group through giving an unpredictable mild stimulus (CUMS). The depressive rats were randomly divided into a model group, an rTMS group and a sham rTMS group (8 cases in each group). The rTMS group and sham rTMS groups accepted the rTMS or sham stimulation for 3 weeks. The changes in behavior in each group were quantified using body weight, sucrose consumption and an open field test before and after stimulation. Enzyme-linked immunosorbent assays (Elisas) were conducted to detect plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. Reverse-transcription polymerase chain reactions (RT-PCRs) were carried out to allow the detection of mRNA expression in hypothalamus related to levels of adrenocorticotropic hormone releasing hormone (CRH). Results After the modeling there were significant differences between the model preparation group and the control group in terms of weight increase, sucrose consumption and open field test results. After rTMS the rate of weight increase, sucrose consumption and the scores in the open field test of the rTMS group had increased significantly more than in the control group. Elisas showed significantly higher plasma ACTH and CORT levels in the model group as well. The average expression of CRH mRNA in the model group was significantly higher than in either of the other two groups. Conclusions rTMS can relieve depression-like behavior induced by chronic stress, at least in rats. This may be related to a downgrading of the hyperactive functioning of the hypothalamus-pituitary-adrenal axis. Key words: Depression; Transcranial magnetic stimulation; Hypothalamus-pituitary-adrenal axis; Stress

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice.

5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and pA2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS-induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain.

Role of hippocampus mitogen-activated protein kinase phosphatase-1 mRNA expression and DNA methylation in the depression of the rats with chronic unpredicted stress.

Stressful life events especially the chronic unpredictable stress are the obvious precipitating factors of depression. The biological information transduction in cells plays an important role in the molecular biology mechanism of depression. Mitogen-activated protein kinase phosphatase-1 (MKP-1) regulates the cell physiological activity and involves in the adjustment of neural plasticity, function, and survival. This experiment tried to explore the possible effects of MKP-1 in hippocampus on depression of rats by determining the expression of MKP-1 mRNA and DNA methylation in MKP-1 gene promoter. The animal model was established by chronic unpredictable stress, and evaluated by open-field test and weight changes. All the rats were divided into the sham stimulation, the physiological saline, and the fluoxetine (1.25, 2.50, and 5.00 mg/kg) groups randomly. The expression of MKP-1 mRNA in the hippocampus was measured by RT-PCR and the methylation of MKP-1 promoter DNA was detected by COBRA. The chronic unpredicted stress (1) increased the animal movement scores in open-field test, and fluoxetine could prevent this increasement; (2) increased the body weight, and fluoxetine could not prevent this increasement; and (3) increased MKP-1 mRNA expression in the hippocampus, and fluoxetine could prevent it. However, fluoxetine did not influence the DNA methylation of MKP-1 gene promoter in the hippocampus during the chronic unpredicted stress. MKP-1 in the hippocampus might be involved in the etiology of depression, and DNA methylation of MKP-1 gene promoter in the hippocampus did not related with the depression.

Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS), and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity.

Recombinant human erythropoietin for repair of white matter damage

Erythropoietin has been shown to exhibit neuroprotective effects in animal models. A neonatal rat model of hypoxic-ischemic white matter damage was established via bilateral carotid artery ligation in 4-day-old Sprague-Dawley rats. The rats were subsequently treated with recombinant human erythropoietin to observe pathological changes in the brain and long-term neurobehavioral functions before and after intervention. Results showed that the number of myelin basic protein-positive cells, which reflected myelin/oligodendrocyte damage, significantly increased, although the number of amyloid precursor protein-positive cells, which reflected axonal injury, significantly decreased in periventricular white matter at 72 hours and 7 days following erythropoietin intervention. The number of glial fibrillary acidic protein-positive cells, indicating astrocytic damage, significantly decreased in periventricular white matter of erythropoietin-treated rats at 48 hours, 72 hours, 7 days, and 26 days. Following erythropoietin intervention in the 30-day-old rats, head-turning time in the slope test was shortened and open-field test scores increased. These results suggested that erythropoietin promoted repair of white matter damage, as well as improved neurobehavioral functions in a rat model of hypoxic-ischemic injury.

Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior.

The use of human umbilical cord blood (hUCB)--a rich source of nonembryonic or adult stem cells--has recently been reported to ameliorate behavioral consequences of stroke. In this study, we tested whether human cord blood leukocytes also ameliorate behavioral impairments of spinal cord injury. Rats were divided into five groups: (1) laminectomy (without spinal cord injury) only; (2) laminectomy + cord blood infusion; (3) spinal cord injury + cord blood infused 1 day post injury; (4) spinal cord injury + cord blood infused 5 days post injury; and (5) spinal cord injury only. Spinal cord injury was induced by compressing the spinal cord for 1 min with an aneurysm clip calibrated to a closing pressure of 55 g. Open-field behavior was assessed 1, 2, and 3 weeks after intravenous injection of prelabeled human cord blood cells. Open-field test scores of spinal cord injured rats treated with human cord blood at 5 days were significantly improved as compared to scores of rats similarly injured but treated at day 1 as well as the otherwise untreated injured group. The results suggest that cord blood stem cells are beneficial in reversing the behavioral effects of spinal cord injury, even when infused 5 days after injury. Human cord blood-derived cells were observed in injured areas, but not in noninjured areas, of rat spinal cords, and were never seen in corresponding areas of spinal cord of noninjured animals. The results are consistent with the hypothesis that cord blood-derived stem cells migrate to and participate in the healing of neurological defects caused by traumatic assault.

Collaborative Behavioral Teratology Study of Phenytoin: A Test Battery for Neurobehavioral Developmental Toxicity in Rats.

Abstract: At the Behavioral Teratology Meeting (BTM) of the Japanese Teratology Society in 1992, a core test battery was proposed from a practical and simple point of view as an estimation of developmental neurobehavioral toxicity for use in pharmaceutical drug screening. The validity of the core test battery is being examined in a new series of collaborative studies. The present study is the first such study; phenytoin, a well‐known behavioral teratogen, was selected as the test compound, and 32 laboratories took part in a behavioral teratology study of phenytoin using the new test battery.Sprague‐Dawley strain rats from four breeds were used. Phenytoin (200 mg/kg) was administered orally to pregnant rats from days 10 to 14 of gestation (sperm detection = day 0), and in the male offspring, the survival rate, development of physical landmarks, functional developments, open field test scores, and Biel water maze test results were assessed and the brain weights were measured. The shuttle box conditioned avoidance test was also performed in some laboratories.In the present collaborative study, by taking an aggregate of the relative values converted from the measured values of each breed (providing a much larger sample size than that recommended by reproduction toxicity study guidelines), a high detectability level for phenytoin's effects was established.Under these conditions, the effects of phenytoin on eye opening, incisor eruption, the surface righting reflex, the negative geotaxis reflex, and performance of the open field test, Biel water maze test and shuttle box conditioned avoidance test were observed. It was found that present collaborative study made it possible to evaluate the detectable capacity of each of these test battery items. In addition, the critical period of abnormalities demonstrated in many test items was identified, and the results of several previous reports were confirmed. Furthermore, a breed difference in the effect of phenytoin for several test items was found.The present results established that the core test battery accurately detected the effects of phenytoin.

Two Types of Strain Differences in Open-Field Behavior in Rats and their Mapping

Abstract Open-field behavior of three treatments for three strains of rats (SD, Long-Evans, Fischer-344) was plotted on a map by component scores that were derived from principal component analysis. The treatments consisted of electric shock, extensive stroking, or testing after habituation to the field. Five measures were used: ambulation, penetration into the inner square, rearing, defecation, and urination. There was a clear strain difference on the basis of a raw open-field test score. This was termed a raw-score strain difference. A treatment-effect strain difference, however, which is obtained by comparing treatment and control conditions, was not clear. Thus, the behavior of each treatment condition cohered clearly with each other on the map, regardless of raw-score strain differences. This indicates that the nature of emotional behavior caused by the present treatments is very similar among strains despite the clear raw-score strain difference.