Influence of vestibular training on plasma levels of stress-related hormones in rats with motion sickness

AIM: To investigate the relationship between motion sickness and the plasma levels of stress-related hormones in the rats before and after vestibular training.METHODS: Conditioned taste aversion (CTA) was induced in 72 female SD rats after rotatory stimulation. The magnitude of CTA was measured to reflect the susceptibility of rats to motion sickness. The plasma levels of corticosterone, adrenocorticotrophic hormone (ACTH), corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) were analyzed by radioimmunoassay. Hormone levels were determined before and after rotatory stimulation, and after 1 month of vestibular training when the rats obtained habituation to this rotation.RESULTS: CTA to 0.15% saccharin solution in rats after the rotatory stimulation was completely inhibited after vestibular training, suggesting that a habituation of the rats to motion sickness was obtained. The rotatory stimulation induced an elevation in the plasma levels of corticosterone, ACTH and AVP, and this response of corticosterone to rotation was greatly reduced after vestibular training. The plasma levels of all 4 hormones in the rats insusceptible to motion sickness were higher than those in susceptible group, especially the plasma levels of corticosterone and ACTH after rotation, and the basal level of CRH. In addition, after vestibular training, the basal plasma levels of corticosterone, ACTH and CRH in both groups were higher than those before training, and a slight elevation was also observed in the basal level of AVP.CONCLUSION: Vestibular training may induce a habituation to rotatory stimulation in rats, thus inhibiting the development of motion sickness. The difference of the susceptibility of rats to motion sickness may negatively relate to the basal plasma levels of stress-related hormones.     

Activation of corticotrophin releasing hormone-containing neurons in hypothalamic paraventricular nucleus contributes to sympathoexcitation in rats with congestive heart failure

AIM:To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS:Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF,and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile,the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks,left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dt_max) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS:Compared with the sham-SD rats,the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased),accompanied by decreased±dp/dt_max and increased RSNA,plasma NE,LVEDP,lung/BW and RV/BW.However,ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats,the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition,they had significantly increased RSNA and plasma NE level,higher LVEDP,RV/BW and lung/BW,and lower±dp/dt_max(P<0.05).Compared with the SHAM-Lewis rats,the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION:In CHF,the CRH-containing neurons in PVN are activated,thus aggravating cardiac function by increasing sympathoexcitation.     

Effect of Jieyuwan on depression-like behaviors and expression of BDNF in hippocampus and prefrontal cortex of WKY rats

AIM:To investigate the mechanism of depression and its development, and to study the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex of Wistar-Kyoto (WKY) rats treated with Jieyuwan. METHODS:Adult male WKY rats were used as an animal model of endogenous depression. Wistar rats of the same strain were selected as control group. WKY rats were randomly divided into model group, citalopram group and Jieyuwan group. After intragastric administration for 21 d, the changes of depression-like behaviors were observed by sucrose preference test and forced swimming test. Immunofluorescence and Western blot were used to detect the expression of BDNF in the hippocampus and prefrontal cortex. RESULTS:WKY rats showed significant depression-like behaviors, and the expression of BDNF was significantly decreased in the hippocampus and prefrontal cortex (P<0.01). The reduction of neuronal axons in hippocampus was also observed. After drug treatment, the depression-like behaviors of WKY rats were significantly attenuated, and the expression of BDNF and the number of axons were increased (P<0.01). CONCLUSION:Jieyuwan effectively attenuates the depression-like behaviors of WKY rats, and BDNF is a key factor in its antidepressant effect. Our findings further confirm the involvement of BDNF in the development of depression.     

Immunohistochemical study on ACTH cells and TSH cells of pituitary pars distails of morphine dependent male rats and its restoration after withdrawal

AIM: To investigate the change of adrenocorticotropic hormone (ACTH) cells and thyroid- stimulating hormone(wn) cells of pars distalls of pituitary gland of morphine dependent dependent rats and its restoration after withdrawal. METHODS: Morphine dependent model of male rats was made by subcutaneous injection of mor- phine and the adstinent model was made after withdrawal. Changes of ACTH cells and TSH cells of pars distails of pituitary gland were detected by immunohistochemistoy survey and image analysis. RESULTS: The intensity of positive staining and the numerical density of ACTH and TSH immunoreactive cells were weakened (P＜ 0.01), after withdrawal from morphine for a short time the changes would exist continuously. CONCLUSION: Morphine may give rise to disorder of endocrine of pituitary gland of male rats, which may incompletely restore after withdrawal for a short time.     

Effects of dexmedetomidine on behaviors and expression of BDNF and mTOR in hippocampus of depressive rats

AIM: To investigate the effects of dexmedetomidine (DEX) on the behaviors and the expression of brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the hippocampus of depressive rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation group, model group, and DEX (2.5, 5 and 10 μg/kg) groups. The rats were randomly selected in each group (n=12). The rat depression model was established by chronic unpredictable mild stress and ovariectomy. The rats in DEX groups received daily DEX treatment via intraperitoneal injection for 21 d. The forced swimming immobility time (FSIT) and open-field test were used to evaluate the antidepressant effect of DEX. Escape latency and times of crossing the flat were evaluated by Morris water maze. The histological changes of hippocampal neurons were determined by Nissl staining. The mRNA levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by RT-qPCR. The protein expression of IL-1β, IL-6, TNF-α and BDNF, and the phosphorylation levels of protein kinase A (PKA), cAMP response element-binding protein (CREB), tropomyosin-related kinase B (TrkB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mTOR in hippocampus were evaluated by Western blot. RESULTS: Compared with model group, the FSIT was significantly reduced and the spontaneous activity was markedly increased in DEX groups. The damage of the hippocampal neurons was obviously attenuated, the escape latency was obviously decreased, and times of crossing the flat were markedly increased (P<0.05 or P<0.01). The levels of IL-1β, IL-6 and TNF-α were obviously decreased, and the protein levels of p-PKA, p-CREB, BDNF, p-TrkB and p-PI3K, p-Akt, p-mTOR in hippocampal tissues were obviously increased (P<0.05 or P<0.01). CONCLUSION: Dexmedetomidine improves the behaviors and the spatial learning and memory ability of depressive model rats, which may be related to its anti-inflammatory effects, as well as up-regulating the protein levels of BDNF and p-TrkB, and activating PI3K/Akt/mTOR signaling pathway in the hippocampus.     

Effects of exogenous ADM on HPA axis in early stage of acute mechanical renal trauma

AIM: To explore the effects of exogenous adrenomedullin(ADM) on hypothalamus-pituitary-adrenal cortex (HPA)axis in the early stage of acute mechanical renal trauma.METHODS: Healthy adult Wistar rats were randomly divided into 4 groups: 8 in control group, 32 in trauma group, 32 in the group injected with ADM before trauma and 32 in the group injected with ADM after trauma. To induce renal trauma, the rats in the latter 3 groups were subjected to mechanical impact directly on the skin of renal region by a free-fall iron hammer. The rats in 2 treatment groups were injected with ADM (0.1 nmol/kg) intraperitoneally 10 min just before and after trauma,respectively. The rats in the 3 groups with kidney injury were executed in batches by drawing all the blood quickly in the hearts at the time points of 1 h, 6 h, 12 h and 24 h after trauma. The hypothalamus tissues were also collected. The expression of corticotropin-releasing hormone(CRH) in hypothalamus and the concentrations of adrenocorticotropic hormone(ACTH) and cortisol(CORT) in plasma were detected by immunohistochemical method and radioimmunoassay. RESULTS: The expression of CRH in hypothalamus and the concentrations of ACTH and CORT in plasma in trauma group,but were slightly higher than those in control group,but without statistical significance. The expression of CRH in hypothalamus at 1 h and 24 h, the concentration of ACTH in plasma at 12 h and CORT at 6 h,12 h and 24 h in the group injected with ADM before trauma significantly higher than those in trauma group and control group (P<0.05). The expression of CRH in hypothalamus at 1 h, 6 h and 12 h and the concentration of CORT in plasma at 12 h and 24 h in the group injected with ADM after trauma were obviously higher than those in trauma group and control group (P<0.05). CONCLUSION: Exogenous ADM stimulates HPA axis and activates the function of HPA axis markedly. However, the different layers of HPA axis have different responses to exogenous ADM. Injection of ADM before or after trauma has different effects on HPA axis.     

miR-381-3p protects hippocampal neurons of depressive rats from injury via BDNF

AIM: To investigate the effect of microRNA (miR)-381-3p on neuronal injury in the hippocampus of depressive rats and the possible regulatory mechanism.METHODS: The rat model of depression was established by subcutaneous injection of corticosterone and the model rats received fluoxetine treatment. The body weight, open field test and biochemical indexes were measured for judging the therapeutic effect of fluoxetine. The expression of miR-381-3p, brain-derived neurotrophic factor (BNDF), Bcl-2 and Bax in the hippocampus was determined. The cultured neonatal rat hippocampal neurons were pre-transfected with miR-381-3p inhibitor and then incubated with corticosterone. The cell viability, and the expression of miR-381-3p, BNDF, Bcl-2 and Bax were detected. The targeted regulatory role of miR-381-3p in BDNF was verified by luciferase reporter assay.RESULTS: Compared with depression group, fluoxetine increased the body weight, the number of cross-field activities and the content of norepinephrine, inhibited the expression of miR-381-3p and promoted the expression of BNDF in the hippocampus. miR-381-3p silencing reversed the effect of corticosterone, resulting in the increase in the survival rate of hippocampal neurons, upregulation of BDNF and Bcl-2, and downregulation of Bax expression. miR-381-3p targeted the regulation of BNDF expression.CONCLUSION: Silencing miR-381-3p protects rat hippocampal neurons from corticosterone injury, and its mechanism may be related to the upregulation of BNDF expression.     

Role of central PGE2 on sympathetic excitation in chronic heart failure

AIM: To observe the effect of central prostaglandin E₂ (PGE₂) on sympathetic activation in chronic heart failure (CHF) and to explore the underlying mechanism. METHODS: Male SD rats were subjected to coronary artery ligation to induce heart failure (HF), and the intracerebroventricular infusion was performed by osmotic pump continuously. The rats in sham group and HF group were given artificial cerebrospinal fluid (0.25 μL/h). The rats in HF plus treatment group was given celecoxib (CLB; 20 mg/h). After 4 weeks, the levels of PGE₂ in cerebrospinal fluid (CSF), the sympathetic nerve excitability and cardiac function were measured, and the changes of corticotropin-hormone releasing hormone (CRH)-containing neurons activation and neurotransmitter contents in the hypothalamic paraventricular nucleus (PVN) were also determined. RESULTS: Compared with the sham-operated rats, the HF rats had raised level of PGE₂ in CSF, up-regulated renal sympathetic nerve activity and plasma norepinephrine, increased left ventricular end diastolic pressure, lung-to-body weight and right ventricular-to-body weight ratios, and decreased maximal increase and decreased rate of left ventricular pressure (P<0.05). In addition, the number of CRH positive neurons in PVN and the level of plasma adrenocorticotropic hormone were higher in HF rats than those in sham-operated rats (P<0.05). After administration of CLB into the lateral ventricle of HF rats, the contents of PGE₂ in CSF were significantly reduced, the number of activation CRH neurons in PVN was decreased, the excitability of sympathetic nerves was down-regulated and cardiac function was improved (P<0.05). Compared with the sham-operated rats, the content of glutamic acid in PVN of HF rats was increased, the content of γ-aminobutyric acid and the number of glutamate decarboxylase 67-positive neurons were decreased (P<0.05). After the CLB was given, the above indexes were reversed (P<0.05). CONCLUSION: These findings indicate that in CHF, the increased central PGE₂ may activate CRH-containing PVN neurons and contribute to the augmented sympathetic drive possibly by modulating the neurotransmitters within the PVN.     

The central role of corticotropin-releasing hormone in stress-induced hyperthermia and LPS-induced fever in rats

AIM:To further investigate the role of central corticotropin-releasing hormone in stress-induced hyperthermia and lipopolysaccharide (LPS)-induced fever in the rat.METHODS:Test substances were administered intracerebroventricularly (icv) via a third ventricle cannula. Body temperature responses were monitored at 30 min intervals using colonic thermistor probes. Arginine vasopressin (AVP) level in the ventral septal area (VSA) determined by radioimmunoassay. RESULTS:In normal saline controls,rats were handled to take the colonic temperature,their body temperature significantly increased with a peak of(0.88±0.31)℃.The injection(icv)of α-helical CRH(9-41),a CRH-41 receptor antagonists,markedly attenuated the stress-induced hyperthermia within 90 min after injection of normal saline.LPS(300 ng,icv)stimulated a biphasic rise in the colonic temperature,the 3.5 h thermal response index(TRI_3.5)and AVP levels in the VSA of LPS-treated rats were higher than those of control rats.The AVP responses to LPS were inhibited significantly by blockade of central CRH actions using α-helical CRH(9-41)(5μg,icv)administered 10 min prior to LPS,whileα-helical CRH(9-41)(5μg,icv)resulted in exacerbated febrile responses to LPS(300 ng,icv). CONCLUSION:Central CRH plays an important role in stress-induced hyperthermia. The injection (icv) of α-helical CRH(9-41) enhances markedly LPS-induced fever in rats. CRH is a dual action molecule in LPS-induced fever, which itself mediates LPS-induced fever, at the same time, and limits the rise in body temperature during fever through actions of AVP in the VSA and glucocoticoids.     

Effect of resveratrol on level of brain-derived neurotrophic factor in hippocampus of obese rats induced by ovariectomy and high-fat diet

AIM：To explore the effects of resveratrol on the level of brain-derived neurotrophic factor (BDNF) and the mRNA expression of estrogen receptor α (ERα) and estrogen receptor β (ERβ) in hippocampus of obese rats induced by ovariectomy and high-fat diet. METHODS：Fifty female Wistar rats, aged 3 months, were randomly divided into 5 groups: control (C) group, sham operation plus high-fat diet (H) group, ovariectomy plus normal diet (O) group, ovariectomy plus high-fat diet (O+H) group, and ovariectomy plus high-fat diet and treated with resveratrol (40 mg·kg-1·d-1) (O+H+R) group. Three months later, the blood was collected from the femoral artery to detect the serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and estradiol (E2). The mRNA expression of ERα, ERβ and BDNF in the hippocampus was determined by real-time PCR. The protein level of BDNF in hippocampal tissues was detected by ELISA and Western blotting. RESULTS：Compared with C group, the serum levels of TC and LDL-C in H group were increased, and the hippocampal level of BDNF was decreased. The rats in O group had higher concentration of serum TC, and lower levels of serum E2 and the mRNA expression of ERα, ERβ and BDNF in the hippocampus than those in C group. Compared with C,H and O groups, the level of serum TC was higher, and the level of serum E2 and the expression of BDNF in the hippocampus was lower in O+H group. The mRNA expression of ERα and ERβ in hippocampus was also reduced as compared with C group and H group. After treated with resveratrol, the rats in O+H+R group showed lower level of serum TC, and higher levels of serum E2, hippocampal BDNF and mRNA expression of ERα and ERβ than those in O+H group. CONCLUSION：Ovariectomy combined with high-fat diet decreases the mRNA expression of ERαand ERβ and the level of BDNF in the rat hippocampus. Resveratrol improves the blood lipid metabolism and up-regulates the mRNA expression of ERα/ERβ and the level of BDNF in the hippocampus in obese rats induced by ovariectomy and high-fat diet.     

Effects of sport fatigue and poverty of movement on neuroendocrine system in Wistar rats

AIM: To observe the different changes of neuroendocrine systems between the state of sport fatigue and poverty of movement. METHODS: 60 male Wistar rats were randomly divided into three groups: normal control group, sport fatigue model group and poverty of movement model group (20 rats in each group). The sport fatigue model was established by the method of combining basal diet and loaded swimming during 2 weeks, whereas the method of restricted activities was used to establish the poverty of movement model with total experimental time of 10 weeks. By the end of experiment, the climbing pole time was determined. The contents of hypothalamus thyrotropin releasing hormone (TRH), and serum norepinephrine (NE) and epinephrine (E) in rats with different treatments were determined by ELISA. In addition, the changes of hypothalamus corticotropin release hormone (CRH), pituitary adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH), and serum corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4) were determined by radioimmunoassay to evaluate the functions of adrenergic nerve-adrenomedullin system, hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-pituitary-thyroid (HPT) axis. RESULTS: Compared to control group, the climbing pole time of the animals was obviously decreased in two model group. The adrenergic nerve-adrenomedullin system and HPA axis were inhibited in sport fatigue model rats, but HPT axis was unchanged. Interestingly, the HPA axis was hyperfunctional and HPT axis was inhibited in poverty of movement model rats. However, no change in the adrenergic nerve-adrenomedullin system was observed. CONCLUSION: Sport fatigue and poverty of movement all affect neuroendocrine system and lead to the adjustment mechanism imbalance, but the target and tendency are different.     

Effect of BDNF expression in cerebral cortex and hippocampus on ability of learning and memory in APP/PS1 transgenic mice

AIM: To investigate the expression changes of brain-derived neurotrophic factor (BDNF) in the cerebral cortex and hippocampus and their effects on the ability of learning and memory in the wild-type (WT) mice and APP/PS1 transgenic mice. METHODS: WT mice and APP/PS1 transgenic mice were selected as study subjects. Aβ plaques, apoptosis rate and BDNF expression in the cerebral cortex and hippocampus of WT mice and APP/PS1 transgenic mice were detected by the methods of Congo red staining, TUNEL, immunofluorescence and Western blot. The abilities of learning and memory were determined by Morris water maze test. RESULTS: The Aβ plaques appeared in the cerebral cortex and hippocampus of APP/PS1 transgenic mice, and the number of Aβ plaques in 12-month-old mice was larger than that in 6-month-old mice (P<0.05). The number of apoptotic neurons in the cerebral cortex and hippocampus of 12-month-old APP/PS1 transgenic mice was larger than that of WT mice (P<0.01). The expression level of BDNF in the cerebral cortex and hippocampus of WT mice was higher than that of APP/PS1 transgenic mice (P<0.01). The Morris water maze test showed that the escape latency in APP/PS1 transgenic mice was longer than that in WT mice, and the times across the platform quadrant in 60 s was less than that in WT mice (P<0.01). The swim-tracking path of APP/PS1 transgenic mice was disordered and irregular. CONCLUSION: The expression of BDNF in the cerebral cortex and hippocampus of APP/PS1 transgenic mice was lower than that of WT mice, accompanied by increased neuronal apoptosis and decreased spatial learning and memory ability. The decrease in learning and memory ability may be related to decreased BDNF expression in the cerebral cortex and hippocampus of APP/PS1 transgenic mice, leading to increased neuronal apoptosis, which may be one of the pathological mechanisms of Alzheimer disease.     

Effects of three Chinese formulas on BDNF,TrkB in rat contex and hippocampus with chronic immobilization stress

AIM: To investigate the changes of brain-derived neruotrophic factor (BDNF), tyrosine kinase B (TrkB) in rat cortex and hippocampus with chronic immobilization stress and the influence of three Chinese formulas (Xiaoyaosan, Sijunzitang, Jinkuishenqiwan) on them. METHODS: Chronic immobilization stress method (180 min daily, repeated 7 days or 21 days) was taken, and the changes of BDNF, TrkB in rat forehead cortex and hippocampus CA1 were measured by immunohistochemistry integrated image analysis. RESULTS: The contents of BDNF in rat forehead cortex and hippocampus CA1 were obviously lower in the model group of 7 days and 21 days than those in the normal control group (P<0.05, P<0.01), especially the lowest in the model group of 21 days. The contents of TrkB in rat forehead cortex and hippocampus CA1 were higher in the model group of 7 days and 21 days than those in the normal control group (P<0.05, P<0.01). All three Chinese formulas increased the intergral absorbance of BDNF in rat cortex and particle number of BDNF in rat hippocampus CA1. The particle number of TrkB in rat hippocampus CA1 and cortex, and intergral absorbance of TrkB in rat hippocampus CA1 were reduced by Xiaoyaosan. The intergral absorbance of TrkB in rat forehead cortex was reduced by Sijunzitang and Jinkuishenqiwan. The particle number of TrkB in rat forehead cortex was decreased by Jinkuishenqiwan. Compared with the influence of BDNF in response to three Chinese formulas, effect of Xiaoyaosan was more remarkable.CONCLUSION: Decreased BDNF in rat forehead cortex and hippocampus CA1 may participate in changes of chronic immobilization stress, and it can be reversed by the Chinese herbs of soothing liver, strengthening spleen, nourishing kidney, but the effect of Xiaoyaosan is better than that of Sijunzitang and Jinkuishenqiwan.     

Myelin-associated glycoprotein inhibits the differentiation and neurite growth of neural stem cells

AIM: To observe the characterization in neural cells derived from the hippocampus of embryonic rats and to examine the effect of myelin-associated glycoprotein (MAG) on the proliferation, differentiation and neurite growth of neural stem cells (NSCs). METHODS: The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expressions of nestin and doublecortin, the marks of NSCs, were observed by immunocytochemical method. The rate of proliferating cells was examined by BrdU immunocytochemistry. The average neuronal neurite length and the percentage of differentiated neurons were detected by immunocytochemistry staining. RESULTS: The hippocampus cells of 16 days old embryonic rats had the characteristics of NSCs. The percentage of differentiated neurons (β-tubulin Ⅲ-positive cells) was 18.17%±2.79% and the average neuronal neurite length was (136.27±33.66)μm, seven days after the differentiation initiated in vitro in control group. After NSCs were treated with MAG-Fc (200 μg/L), the percentage of differentiated neurons and the average neurite length were decreased, respectively, to 10.05%±3.42% (P<0.01) and (84.87±24.94)μm (P<0.01). The results from proliferation test indicated that the rate of BrdU incorporation did not changed after the treatment of MAG-Fc with different dosages (P>0.05). CONCLUSION: MAG-Fc inhibits the differentiation and neurite growth of the NSCs, but has no effect on the proliferation.     

Changes of cortisol content in plasma and hippocampus after focal cerebral ischemia-reperfusion in rats

AIM: To investigate the relationship between glucocorticoid (Gc) and injury of hippocampus neurons and the effect of Gc on dementia episode after cerebral ischemia-reperfusion. METHODS: The rat model of middle cerebral artery occlusion (MACO) was established. Cortisol contents in hippocampus and plasma of the model rats were examined by means of the radioimmunoassay at 2 h, 6 h, 12 h, 24 h after reperfusion. RESULTS: The levels of cortisol content in model group were significantly higher than those in sham group and normal group both in hippocampus and plasma. The highest cortisol content was observed at 6 hours after reperfusion. HE staining showed that the impairment of hippocampus neurons was aggravated progressively with reperfusion interval elongating. CONCLUSION: The increased cortisol in hippocampus and plasma, after 2 h cerebral ischemia and 24 h reperfusion, could aggravate the injury of hippocampus neurons and lead to dementia post stroke.     

Urocortin,a novel peptide of the corticotropin releasing hormone family

Urocortin, a novel peptide of the cortiotropin releasiong hormone (CRH) family, was discovered in 1995 in the rat brain and subsequently cloned and localized to human chromosome 2. It can bind to both CRH type 1 receptor and CRH type 2 receptor, as well as CRH binding protein. Especially to CRH type 2 receptor, urocortin binds to it with 40 times more potency than CRH does. Therefore, urocortin is thought to be an en dogenous ligand for CRH type 2 receptor. Immunoreactive urocortin and urocortin mRNA were localized in many areas such as mammalian brain, cardiovascular system, placenta. It is believed that urocortinmay play important physiological roles as a neuropeptide not only in the central nervous system but also in peripheral tissues.     

Hyperbaric oxygen therapy activates CREB/BDNF signaling pathway to reduce synaptic damage in hippocampal neurons of Alzheimer disease mice

AIM To investigate the effect of hyperbaric oxygen (HBO) on synaptic damage of hippocampal neurons in APP/PS1 transgenic (TG) mice and its possible mechanism. METHODS The 6-month-old male APP/PS1 TG mice were randomly divided into TG group, HBO group and cAMP response element binding protein (CREB) inhibitor H89 group, with 10 mice in each group. Ten male wild-type (WT) C57BL/6 mice of the same age were used as negative control group (WT group). The mice in HBO and H89 groups were treated with HBO for 6 cycles, while the mice in WT group and TG group were not treated. The learning and memory abilities were observed by Morris water maze. The nesting ability of the mice was detected by nesting test. The Nissl bodies in hippocampal neurons were observed by Nissl staining. The mRNA expression of CREB and brain-derived neurotrophic factor (BDNF) in hippocampus was detected by real-time PCR. The protein levels of synapsin (SYN), postsynaptic density protein 95 (PSD95), growth-associated protein 43 (GAP43), CREB, phosphorylated CREB (p-CREB) and BDNF in the hippocampus were determined by Western blot. RESULTS Compared with WT group, the learning and memory abilities of the mice in TG group were signilficantly reduced (P<0.05). In addition, the nesting score, the number of Nissl bodies in the hippocampal neurons, the mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P<0.05). Compared with TG group, the learning and memory abilities of the mice in HBO group were improved (P<0.05). Meanwhile, the nesting scores of the mice were significantly increased (P<0.05), the neurons in the hippocampus were arranged neatly, and the number of Nissl bodies, the relative mRNA expression of CREB and BDNF,and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also increased significantly (P<0.05). Compared with HBO group, the mice in H89 group had poor learning and memory abilities, lowered nesting scores and decreased number of Nissl bodies. Futhermore, the relative mRNA expression of CREB and BDNF, and the protein levels of SYN, PSD95, GAP43, p-CREB and BDNF were also decreased significantly (P<0.05). CONCLUSION HBO improves the learning and memory abilities of APP/PS1 TG mice, and its mechanism may be related to activating the CREB/BDNF signaling pathway to reduce synaptic damage of hippocampal neurons in mice.     

Artificial Calculus Bovis inhibits neuron loss in hippocampus and hilus and protects the GAD positive cells in hippocampus of epileptic rats

AIM:To probe into the anti-epilepsy action of artificial Calculus Bovis, by observing its effect on the behavioral of the experimental epileptic rats, neuron loss in the hippocampus and hilus, and GAD positive cell alteration in the hippocampus. METHODS:SD rats were divided into three groups:group A (artificial Calculus Bovis treatment group);group B (acute epilepsy group) and group C (control group). A model of acute epilepsy rats was established by PTZ. The rat’s behavioral alteration was observed by the Racine’ scale. The neurons in the hippocampus and hilus were calculated by Nissl staining. The GAD positive cells were observed by immunohistochemical staining. RESULTS:The latency of the first seizure in group A was longer than that in group B, while the seizure times in group A was less than that in group B. Besides, in group A, both the neuron loss amount in the hippocampus and hilus and the GAD positive cell loss amount in the hippocampus were less than those in group B. CONCLUSION:The artificial Calculus Bovis prolonged the latency of the first seizure time, decreased the frequency of seizure, and prevented the neuron loss and protected the GAD positive cells.