Sucrose Water Consumption Research Articles

Mechanism of Treadmill Exercise Combined with Rich Environmental Stimulation to Improve Depression in Post-stroke Depression Model Rats.

Post-stroke depression (PSD) is a common complication, occurring in approximately one-third of these patients. The neurological symptoms of PSD affect patients' daily life and subsequent recovery. Analyzing the pathogenesis of post-stroke depression from a psychological perspective, it was found that PSD patients often feel despair and anxiety, and it is crucial to explore non-pharmacological ways to improve post-stroke depressive symptoms. A combination of exercise and rich environmental stimulation (RES) has been found effective in improving post-stroke depressive symptoms. Therefore, this study aimed to explore the effects of exercise and rich environmental stimulation on PSD in rats and their potential underlying mechanisms and to provide a theoretical basis for managing PSD. The PSD rat model was constructed, and the depression-like behaviors of rats in each group were evaluated using the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Moreover, changes in the morphological behavior of rat hippocampus were observed using hematoxylin-eosin (HE) staining and Nissl staining. The expression levels of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hippocampus tissues were assessed using enzyme linked immunosorbent assay (ELISA), and the levels of tryptophan-related proteins were determined employing western blot analysis. Additionally, a kynurenine-3-monooxygenase (KMO) inhibitor was administered to the combined stimulation group, and the levels of tryptophan (TRP), 5-HT, kynurenine (KYN), 3-hydroxy-kynurenine (3-HK), and quinolinic acid (QA) were evaluated using liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS). Treadmill exercise combined with rich environmental stimulation significantly reduced the immobility time in the FST (p < 0.01), increased the exploratory behavior in the OFT (p < 0.05), and increased the sucrose water consumption in the SPT (p < 0.01), indicating that the depression-like behavior was improved. Treadmill exercise combined with rich environmental stimulation also improved the shape of the damaged hippocampus and increased the number of neurons in the hippocampus. Additionally, treadmill exercise combined with rich environmental stimulation significantly increased the levels of 5-HT and NE in hippocampus tissues (p < 0.01) and decreased KMO protein level (p < 0.01). In the KMO inhibitor group, the neural function was efficiently restored, the levels of 3-HK, QA, and KMO in the hippocampus were substantially reduced (p < 0.01), and the expression level of 5-HT was increased (p < 0.01). Exercise stimulation combined with enriched environmental stimuli alleviates post-stroke depression in rats, and the underlying mechanisms may be related to TRP/KYN/3-HK/QA excitotoxicity pathways and increased 5-hydroxytryptamine levels.

Consumption of sucrose in maternal and postnatal stages leads to kidney affectation in adult male rats

High sugar-sweetened beverage intake has been related to human kidney disease and metabolic alterations. We determine the impact of high sucrose intake from pregnancy until early postnatal days and post-weaning on kidneys from adult male offspring rats. Wistar female rats were mated and assigned into two groups: one control drinking tap water (CM) and another drinking 5 % sucrose diluted in water (SM). Two offspring per mother were randomly allocated into two experimental groups at weaning. One had free access to simple water (CO) and the other to 5 % sucrose (SO) for 14 weeks. After treatment, levels of relative aquaporin-2 (AQP2), glomerulosclerosis index (GI), collecting tube area, perirenal fat, blood creatinine, and blood ureic nitrogen concentration (BUN) were determined. Two-way ANOVA followed by Bonferroni post-hoc test was used, considering P ≤ 0.05 as a significant statistical difference. Sucrose consumption during gestation/lactation and interaction increased AQP2 expression in the renal cortex and BUN concentration. In contrast, gestation/lactation consumption increased collecting tube area, post-weaning consumption favored perirenal fat, and finally, gestation/lactation, post-weaning, and the interaction caused glomerulosclerosis. Our results suggest that the consumption of sucrose water during gestation/lactation or post-weaning or combination triggers pathological changes in the kidneys of adult rats.

The expression of ProBDNF and its high affinity receptor P75NTR in the neurons of emotion-related brain regions of post-stroke depression rats

ObjectiveTo investigate the expression of the precursor of brain-derived neurotrophic factor (proBDNF) and its high-affinity receptor p75NTR in neurons of emotion-related brain areas (prefrontal cortex, hippocampus, and amygdala) in rats with post-stroke depression (PSD), and to explore the expression levels of proBDNF and p75NTR in neurons of emotion-related brain areas by injecting tissue plasminogen activator (t-PA) into the lateral ventricle of PSD rats, this significantly improved the stress-induced depression-like behavior,thus further validating the above results. MethodsRats were randomly divided into four groups: a normal control group (n = 8), a depression group (n = 8), a stroke group (n = 8), and a PSD group (n = 8). The rat model of stroke was established by thread embolism, and the PSD animal model was induced by chronic unpredictable mild stress (CUMS) and solitary feeding. Behavioral tests were conducted, including weight measurement, open field tests, and sucrose preference tests. Immunofluorescence double labeling was used to detect the expression of proBDNF and p75NTR in neurons of emotion-related brain regions in the PSD rat model. Four weeks after CUMS treatment, the PSD group was selected. Rats were infused with t-PA (3 μg dissolved in 6 μL saline, Boehringer Ingelheim), proBDNF (3 μg dissolved in 6 μL saline, Abcam), or equal-volume NS once per day for 7 consecutive days using the syringe pump connecting to injection needles. After 7 days of continuous administration, animal behavior was assessed through scoring, and the expression of proBDNF and p75NTR in the emotion-related brain regions of the PSD rat model was detected using immunofluorescence double labeling. ResultsCompared with the normal control group and the stroke group, the body weight, sucrose water consumption, and vertical movement distance in the PSD group were significantly lower (P < 0.05). In contrast, when compared with the proBDNF injection group and saline injection group, the weight, sucrose water consumption, field horizontal movement, and vertical movement distance of the t-PA injection group significantly increased after PSD lateral ventricle intubation.Double immunofluorescence revealed a higher neuronal expression of proBDNF as well as p75NTR in the prefrontal cortex and hippocampus of PSD rats compared to control animals (P < 0.05). In the amygdala, the expression levels of proBDNF and P75NTR were significantly reduced in the PSD group compared to the control group (P < 0.05). The results of the expression levels of proBDNF and P75NTR in the emotion-related brain regions of PSD rats injected with t-PA showed that proBDNF and P75NTR was significantly reduced in the prefrontal cortex, hippocampus, and amygdala of PSD rats compared to those of the NS and proBDNF groups (P < 0.05). ConclusionsThe increased expression of the brain-derived neurotrophic factor precursor proBDNF and its receptor p75NTR in neurons of emotion-related brain regions may play an important role in the pathogenesis of PSD.t-PA reduced the expression of proBDNF and its receptor p75NTR in neurons emotion-related brain regions and significantly improved the stress-induced depression-like behavior. Therefore, it is reasonable to assume that exogenous injection of t-PA may alleviate the depressive symptoms of PSD patients.Reducing the expression of proBDNF by injecting t-PA may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Gramine and zingerone mitigates neuroinflammation related depressive behaviour induced by chronic unpredictable mild stress in rat

Depression is a serious mental illness characterised by sadness, a depressed mood, and anhedonia. It is also associated with oxidative stress and inflammatory biomarkers. The chronic unpredictable mild stress (CUMS) model mimics this type of depression. The effects of zingerone (Zn) and gramine (Ga) on CUMS types of depression have not yet been studied, and the effect of drugs on neuroinflammation is also not clear. So we conducted this study. Induction of depression by different stressor procedures after 60 minutes of Zn (75, 125, and 250 mg/kg), Ga (13, 27.5, and 55 mg/kg), and Ecitalopra (15 mg/kg) given daily to rats for successive 21 days The sucrose preference (SP) test and the force swim test (FST) were used to evaluate antidepressant behavioural studies. Observation of the SP test showed a decrease in consumption of sucrose water in the stressor group, with treatment Zn and Ga showing an increase in consumption of sucrose water. In the stressor group, FST immobility time was prolonged; higher doses of Ga and Zn lowered FST immobility time significantly. Treatment with Ga and Zn successfully restored the stressor group's high MDA level and decreased GSH level. The neurotransmitter 5-HT declined in the stressor group, while Ga (27.5, 55 mg/kg) dosages significantly raised it. Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) were pro-inflammatory cytokines that increased in the stressor group, whereas Ga and Zn both dropped these levels at higher doses. We assumed Zingerone and Gramine were good antidepressants against the CUMS depression model.

The ethanolic extract of peanut shell attenuates the depressive-like behaviors of mice through modulation of inflammation and gut microbiota

Peanut shell is an agricultural byproduct being wasted on a large scale, which is in urgent need to be recycled. To fully utilize its pharmacological ingredients, e.g. luteolin, eriodyctiol, and 5,7-dihydroxychromone, we evaluated the curative effect of ethanol extract deriving from peanut shell (PSE) in treating chronic unpredictable mild stress (CUMS)-induced depressive mice. The chronic stress lasted for 10 weeks, and PSE at 100–900 mg/kg/day was gavaged to mice in the last 2 weeks of modeling. The depressive behaviors were assessed by analyses of sucrose preference, tail suspension, and forced swimming. The brain injury was demonstrated by Hematoxylin and Eosin (H&E), Nissl body, and TdT-mediated dUTP nick end labeling (TUNEL) stainings in the mouse hippocampus. Biochemical indicators were analyzed, including levels of neurotrophic factors, neurotransmitters, stress hormones, and inflammatory mediators. The feces were collected for the 16S rDNA sequencing of gut microbiome. Administration of PSE improved the sucrose water consumption of depressive mice, while it decreased the immobile time in tail suspension and forced swimming tests. Meanwhile, the anti-depressive effect of PSE was supported by ameliorated histochemical staining, increased levels of neurotrophic factors and neurotransmitters, as well as down-regulated stress hormones. Furthermore, the treatment of PSE was able to mitigate the levels of inflammatory cytokines in brain, serum, and small intestine. Besides, the tight junction proteins, e.g., occludin and ZO-1, of gut showed elevated expressions, which coincided with the elevated abundance and diversity of gut microbiota upon PSE treatment. This study validated the therapeutic efficacy of PSE in fighting against depression, as well as its modulatory action on inflammation and gut microbiota, which promoted the recycling of this agricultural waste to be health supplements of added value.

Effect of Tongdu Tiaoshen acupuncture on CREB/BDNF/TrkB signaling pathway of hippocampus in rats with post-stroke depression

To observe the regulative effect of Tongdu Tiaoshen acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD. A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area. Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (P<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (P<0.05), MDA level in hippocampal CA1 area was increased in the model group (P<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (P<0.05), MDA level was decreased in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (P<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (P<0.05). Tongdu Tiaoshen acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.

Effect of Electroacupuncture at Siguan Acupoints on Expression of BDNF and TrkB Proteins in the Hippocampus of Post-Stroke Depression Rats.

To study the effect of electroacupuncture at the Siguan acupoints on the expression of hippocampal brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in post-stroke depression (PSD) rats, in order to explore its possible mechanism Fifty specific pathogen-free (SPF)-grade adult male Sprague-Dawley (SD) rats were randomly divided into a blank group, stroke group, PSD group, Siguan acupoint group and fluoxetine group according to the random number method. PSD rats were modeled with middle cerebral artery occlusion combined with chronic unpredictable mild stress. After successful modeling, electroacupuncture was applied to Siguan acupoints for a total of 21days at 30min/session/day. The rats in the fluoxetine group were fed intragastrically according to body weight, once a day, for a total of 21days. The rats in each group were bound and intragastrically administered distilled water every day. The depressive behavior of rats was measured according to the horizontal and vertical scores of the open field test and the sucrose water consumption, and the changes in the number of BDNF- and TrkB-positive cells in the hippocampus of rats were observed by immunohistochemistry. After modeling, the behavioral indicators and the numbers of BDNF- and TrkB-positive cells in each model group were significantly lower than those in the blank group (P < 0.01). After treatment, the behavioral indicators and the numbers of BDNF- and TrkB-positive cells in the Siguan acupoint group and fluoxetine group were significantly higher than that in the PSD group (P < 0.01). During the treatment, the horizontal and vertical scores of the Siguan acupoint group were significantly increased on the seventh day of treatment, and the difference was statistically significant when compared with the PSD group (P < 0.05). The sucrose water consumption was significantly increased on the 14th day of treatment, and the difference was significant when compared with the PSD group (P < 0.05), both of which were earlier than that in the fluoxetine group. During the treatment, there was no significant difference between the two groups (P > 0.05). Electroacupuncture at Siguan acupoints has the same antidepressant effect as fluoxetine, and is more effective than fluoxetine in relieving depression in PSD rats. Its mechanism may be related to the activation of the expression of BDNF and its receptor TrkB.

Sucrose exposure during gestation lactation and postweaning periods increases the pubococcygeus muscle reflex activity in adult male rats.

Erectile dysfunction is related to metabolic alterations produced by a high carbohydrate diet, which may affect muscle activity during penile reflex in adulthood. We determined whether sucrose water consumption during gestation lactation and postweaning affects pubococcygeus muscle (Pcm) activity during urethrogenital reflex in adult male rat offspring. Twelve female rats were mated and grouped in control mothers consumed tap water and sucrose mothers consumed sucrose water during gestation lactation. Male pups were weaned and assigned into four groups (n = 6 each): those from control mothers who continued drinking tap water (CM-CO group) or sucrose water (CM-SO group) until adult life, and those from sucrose mothers who drank tap water (SM-CO group) or continued drinking sucrose water (SM-SO group) until adult life. Body weight, Pcm activity during penile stimulation by bipolar electrodes and urethrogenital reflex were analyzed. A catheter was placed into the urethra to record variations in urethral pressure after mechanical stimulation. Two-way ANOVA followed by post hoc tests were used considering P ≤ 0.05 as a significant difference. Males from the SM-SO group showed weight gain compared to the control group (P < 0.001). Also, sucrose intake promoted high Pcm activity (P < 0.0001) but reduced urethrogenital reflex duration CM-CO vs CM-SO (P = 0.02); CM-CO vs SM-CO (P = 0.01); CM-SO vs SM-SO (P < 0.003); and SM-CO vs SM-SO (P < 0.002). Our results suggest that a combination of a sucrose-rich diet during gestation lactation and postweaning modifies Pcm activation during penile reflex. The urethrogenital reflex is a spinal ejaculatory-like reflex, these rats could have penile dysfunction equivalent to premature ejaculation in men.

Xiaoyaosan improves depressive-like behaviors by regulating the NLRP3 signaling pathway in the rat cerebral cortex

Abstract Objective To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3 (NLRP3) pathway in depressed rats after treatment with Xiaoyaosan, and identify the regulatory mechanism of this compound. Methods Male Sprague–Dawley rats were randomly divided into five groups with 12 rats in each group, including the control group, model group, Fluoxetine group, Xiaoyaosan group, and MCC950 group. A depression model was generated by chronic immobilization stress (induced by 3 h of restraint immobilization every day), and the drugs were administered at the same time in each group for 21 days. The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization, body mass, open field experiments, and a sucrose preference test. The mRNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays. Results The Xiaoyaosan group, Fluoxetine group, and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption. The protein and mRNA expression levels of NLRP3, Caspase-1, and IL-1β were also decreased in the Fluoxetine, Xiaoyaosan, and MCC950 groups. Conclusion NLRP3, Caspase-1, and IL-1β protein and mRNA expression levels were increased in the cortex of depressed rats, while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3, Caspase-1, and IL-1β protein and mRNA expression.

Ferulic acid alleviates lipopolysaccharide-induced depression-like behavior by inhibiting inflammation and apoptosis

Objective: To identify the anti-depressive effect of ferulic acid (FA) in mice exposed to lipopolysaccharide (LPS) and explore its molecular mechanisms.Methods: The mice were divided into 5 groups as follows: Control, LPS, LPS + SP, LPS + FA, and LPS + FA + anisomycin. The LPS + FA and LPS + FA + anisomycin groups were administered with FA (100 mg/kg, i.p.) once daily continuously for 7 days, and the other groups received an equivalent volume of saline. On the 7th day, LPS (0.1 mg/mL, i.p.) was injected in all mice except the control group 30 min after FA or saline administration. The LPS + SP and LPS + FA + anisomycin groups were intravenously administered with SP600125 [c-Jun N-terminal kinase (JNK) inhibitor] (100 μL/ site, i.v.) and anisomycin (JNK activator) (100 μL/site, i.v.) 15 min before LPS, respectively. The depressive behaviors were assessed by open field test, sucrose preference test, and forced swimming test at 24 h post-LPS administration. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in plasma were measured by ELISA. The levels of phospho-JNK, TNF-α, IL-1β, Bcl-2, Bax, cytochrome c and caspase-3 were evaluated by Western blotting.Results: FA alleviated depression symptoms caused by LPS in mice, including increasing sucrose water consumption in sucrose preference test and reducing the immobility time in forced swimming test. FA could inhibit upregulated levels of phospho-JNK, TNF-α, and IL-1β. FA also markedly decreased Bax, caspase-3, and cytochrome c, and increased Bcl-2 levels. Besides, SP600125 showed neuroprotective effect similar to FA which was attenuated by anisomycin.Conclusions: FA attenuates inflammation and apoptosis by inhibiting LPS-induced activation of JNK to alleviate depressionlike behaviors.

Protective effects on hippocampal neurons and the influence on hippocampal monoamine neurotransmitters with acupuncture for promoting the circulation of the governor vessel and regulating the mental state in rats with post-stroke depression

To observe the effects on hippocampal neuronal structure and hippocampal monoamine neurotransmitters such as norepinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) with acupuncture for promoting the circulation of the governor vessel and regulating the mental state (Tongdu Tiaoshen acupuncture) in rats with post-stroke depression and explore the underlying effect mechanism of Tongdu Tiaoshen acupuncture on post-stroke depression. A total of 48 clean-grade SD rats were randomized into a sham-operation group, a model group, a Tongdu Tiaoshen acupuncture group and a non-meridian-non-acupoint group, 12 rats in each one. In the model group, the Tongdu Tiaoshen acupuncture group and the non-meridian-non-acupoint group, the compound method of cerebral medial arterial occlusion and the chronic unpredictable mild stress was adopted to prepare the model of post-stroke depression. In the sham-operation group, skin was opened and the fascia muscle was separated, after artery exposed, no ligation was operated and the incision was sutured directly. In the sham-operation group and the model group, no any intervention was performed. In the Tongdu Tiaoshen acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Shuigou" (GV 26), "Shenting" (CV 24) and "Dazhui" (GV 14) for 40 min in each treatment and the needles were manipulated at the acupoints once in 20 min. The treatment was given once a day, 6 times a week for 4 weeks consecutively. In the non-meridian-non-acupoint group, the depression between the 3rd and 4th metatarsal bones on the dorsum of the forelimb was selected in intervention and the needling technique was same as the Tongdu Tiaoshen acupuncture group. The behavioral changes were observed after intervention in each group. Using transmission electron microscopy, the ultrastructure of hippocampal CA 1 neurons was observed in the rats of each group. Using high performance liquid chromatography, the contents of NE, 5-HT and DA were determined. Compared with the sham-operation group, the Zea-longa neurobehavioral score was increased (P<0.01), the sucrose water consumption was reduced (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were reduced (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was aggravated and the contents of NE, 5-HT and DA were reduced in the model group (P<0.01). Compared with the model group, the Zea-Longa neurobehavioral score was reduced (P<0.01), the sucrose water consumption was increased (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (P<0.01, P<0.05). Compared with the non-meridian-non-acupoint group, the Zea-Longa neurobehavioral score was reduced (P<0.01), the sucrose water consumption was increased (P<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both P<0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (P<0.01, P<0.05). The Tongdu Tiaoshen acupuncture improves the behavior of the model rats with post-stroke depression, repairs hippocampal neuronal damage, which is probably related to the contents of hippocampal monoamine neurotransmitters (NE, 5-HT and DA).

The effects of running exercise on oligodendrocytes in the hippocampus of rats with depression induced by chronic unpredictable stress

Running exercise has been shown to be associated with decreased symptoms of depression. However, the mechanisms underlying these antidepressant effects of running exercise remain relatively unclear. In the current study, we investigated the relationship between depressive symptoms in chronic unpredictable stress (CUS) model rats treated with running exercise and changes in oligodendrocytes in the hippocampus. After 4 weeks of CUS, the model group was randomly divided into a CUS standard group (18 rats) and a CUS running group (15 rats). Then, a 4-week treadmill running trial was performed with the CUS running group. In addition, the behavioral effects of exercise were investigated by means of a sucrose preference test (SPT) and an at the end of the 8th week. Immunohistochemical methods and modern stereological methods were used to precisely quantify the total number of 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase)-positive (CNPase+) oligodendrocytes in each hippocampal subregion. At the behavioral level, after four weeks of running, the CUS running group displayed significantly higher consumption of sucrose water in the SPT than the CUS standard group. Unbiased stereological analyses revealed significantly higher total numbers of CNPase+ cells in the hippocampal CA3 and dentate gyrus regions in the CUS running group than in the CUS standard group, whereas there was no significant difference between the groups in the number of CNPase+ cells in the hippocampal CA1 region. The present results further confirm that exercise can alleviate symptoms and protect hippocampal oligodendrocytes in depressed rats.

The Effect of Traditional Chinese Medicine Zhike-Houpu Herbal Pair on Depressive Behaviors and Hippocampal Serotonin 1A Receptors in Rats After Chronic Unpredictable Mild Stress.

Zhike-Houpu herbal pair (ZKHPHP) is a well-known Chinese medicine to treat gastrointestinal motility dysfunction. Recently, many researchers have found that some of the compounds of ZKHPHP such as meranzin hydrate and magnolol have antidepressant effects. However, little is known about the antidepressant mechanism of ZKHPHP. Therefore, the main aim of the study is to evaluate the antidepressant-like effects of ZKHPHP and its possible mechanism of action on 5-hydroxytryptamine receptor 1A (HTR1A) in the hippocampus CA1 region in rats exposed to chronic unpredictable mild stress. Male Sprague Dawley rats were randomly divided into the following six groups: normal, model, ZKHPHP (3 g/kg), ZKHPHP (10 g/kg), ZKHPHP (20 g/kg), and ZKHPHP (30 g/kg); n = 8 per group. We exposed the rats to chronic unpredictable mild stress and then assessed antidepressant-like effects of ZKHPHP by measuring weight change, observing the open-field test, and measuring sucrose water consumption. The antidepressant mechanism was examined by measuring the effect of ZKHPHP on HTR1A protein expression and HTR1A mRNA expression in the hippocampus CA1 region by using immunohistochemistry analysis, Western blotting, and real-time reverse transcription-polymerase chain reaction. ZKHPHP (10 or 20 g/kg) reduced the incidence of depressive-like behaviors and increased HTR1A protein and HTR1A mRNA expression in the hippocampus CA1 in rats displaying depressive behavior, whereas ZKHPHP (3 or 30 g/kg) had no obvious effect on the measured depression indicators. These data show that ZKHPHP has antidepressant-like effects based on a chronic unpredictable mild stress-induced depression model in rats. ZKHPHP may be attractive as an antidepressant because of its beneficial effects on depression and the absence of gastrointestinal dysregulation, which is a frequently observed unintended effect of many commonly used antidepressive medications.

Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model.

Effects of enriched environment (EE) combined with fluoxetine in a chronic unpredictable stress (CUS) rat model were examined in our study. Thirty male Sprague-Dawley rats were randomly divided into control group, CUS group, CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine group (n=six per group). Rats in the CUS group were bred under conditions of CUS and separation for 6 weeks; Control group animals were bred in group cages (three rats per cage) under standard laboratory conditions for 6 weeks; Rats in CUS+EE group, CUS+fluoxetine group, and CUS+EE+fluoxetine groups were bred under the conditions of CUS and separation for 6 weeks and had an intervention of EE, an oral gavage of fluoxetine, and an intervention of EE+oral gavage of fluoxetine, respectively, every day for the final 3 weeks. Every rat underwent a behavioral assessment at the beginning of the 1st week, at the end of the 3rd week and at the end of the 6th week. Behavioral assessments included sucrose water consumption, weight measurement, and an open field test (measuring horizontal moving distance, rearing behavior, and defecation). Finally, the level of synaptophysin expressed in the hippocampus was measured with immunohistochemistry. We found that EE, fluoxetine, and EE+fluoxetine all reversed the depression-like behaviors of CUS rats. The effect of EE+fluoxetine appeared to be superior to EE or fluoxetine alone; the expression level of synaptophysin in CA1, CA3, and DG of the hippocampus was decreased in CUS rats, however, exposure to EE, fluoxetine, and EE+fluoxetine all reversed this decrease.

Cerebellar Fastigial Nucleus Electrical Stimulation Alleviates Depressive-Like Behaviors in Post-Stroke Depression Rat Model and Potential Mechanisms

Objective: To identify the molecular mechanism of post-stroke depression (PSD), and observe the therapeutic effects of cerebellar fastigial nucleus electrical stimulation (FNS) on the behaviors and regional cerebral blood flow (rCBF) in a PSD rat model. Methods: Healthy SD rats were randomly divided into four groups (sham, stroke, post-stroke depress and FNS group). Sham group (n = 6) underwent sham operation. The other three groups (n = 6*3) underwent MCAO. Rats were examined twice a week in open filed test. Moreover, neuroprotective effect on cerebellar Purkinje cells and expression of cytokines in hippocampal tissue were examined. Results: The PSD group showed a significant weight loss, decreased consumption of sucrose water, reduced rearing and locomotor activities. The FNS significantly alleviates the body weight loss and sucrose preference, locomotor and rearing activities. The bilateral rCBF was also restored after FNS treatment. Moreover, FNS improved the neuroprotection via suppressing apoptosis of cerebellar Purkinje cells. And the inflammatory cytokines mRNA level in hippocampus was significantly decreased. Conclusion: FNS treatment alleviates depressive-like behaviors and rCBF in PSD rats model, which could be attributed to its ability to protect cerebellar Purkinje cells and decrease the mRNA level of inflammatory cytokines.

The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats

Ethnopharmacological relevanceChaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS׳s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress. Materials and methodsSD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9g/kg·d); (2) Component I (3.3g/kg·d); and (3) Component II (2.6g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5ml/kg·d). ResultsDepressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats׳ hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured. ConclusionsCSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS׳s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.

Antidepressant-like activity of Chaihu-Shugan-San aqueous extract in rats and its possible mechanism.

Background:Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal formula, is commonly used for the treatment of depression in China. However, the molecular mechanism underlying its antidepressant action is unknown.Objective:The objective of this study is to evaluate the antidepressant-like effects of CHSGS and further explore the possible molecular mechanism implicated in its actions.Materials and Methods:The rats were randomly divided into four groups: The normal control group, the model control group, the CHSGS group and the fluoxetine control group. The antidepressant-like effects of CHSGS aqueous extract were assessed in rats exposed to chronic mild stress (CMS) using the open-field test and sucrose water consumption test, its underlying mechanism of anti-depression was explored by determining the effect of CHSGS on the extracellular signal-regulated kinase (ERK) and phospho-ERK (P-ERK) in the hippocampus using western blot. The aqueous extract of CHSGS at a dose of standard (5.9 g/kg·d) was administered intragastrically for 14 days during the CMS model while the fluoxetine control group was given at the same time using fluoxetine hydrochloride (1.8 mg/kg·d).Results:The stressed rats demonstrated decreased locomotor activity in open field test and reduction in sucrose consumption and decreased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in the hippocampus. CHSGS alleviated the depressive-like behaviors and increased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in stressed rats as well as fluoxetine.Conclusion:In summary, these results suggest that CHSGS aqueous extract possesses an antidepressant-like activity in CMS induced depression model rats, which might be mediated, at least in part, by reversing the stress-induced disruption of ERK activity.

Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

A bioactive compound from Paecilomyces tenuipes (BCPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress (CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis. The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21. Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone (CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test. Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR. BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

Voluminous sucrose consumption in female rats: increased "nippiness" during periods of sucrose removal and possible oestrus periodicity.

In a two-bottle paradigm in which water and 10% sucrose water were always available, female rats drank about 200 cc of the sugar water (about 65 g of sucrose/kg) per day for 4 wk. There were no significant decreases in consumption over this time. In Exp. 2 female rats singly housed were given two bottles containing water for 1 wk. and then a bottle containing water and a bottle containing 15% sucrose for the next week for 6 wk. When sucrose was available, the rats ate 33% more rat chow. When sucrose was removed, the rats displayed more episodes of biting a stimulus when the food cubes were being removed for daily measurements. Some females exhibited a marked 4- to 5-day periodicity in sucrose (7.5%) consumption. The persistent and voluminous consumption of sucrose water and enhanced agonistic-like behavior during periods of withdrawal suggests the presence of a robust phenomenon with potential dinical applications to the challenge of addiction.

Toxicity and repellency of borate-sucrose water baits to Argentine ants (Hymenoptera: Formicidae).

The oral toxicity of boron compounds to the Argentine ant, Linepithema humile (Mayr), was evaluated in laboratory tests. The ants were provided 25% sucrose water containing 0.5 and 1% boric acid, disodium octaborate tetrahydrate, and borax. Lethal times of these solutions were a function of the concentration of boron. In field tests, the ants showed no discrimination between disodium octaborate tetrahydrate and boric acid. There was a significant reduction in consumption of sucrose water with > 1% boric acid.