Objective To investigate the effects of formononetin (FMN) on cognitive behavior and inflammation in aging rats with chronic unpredictable mild stress (CUMS). Methods SD rats aged about 70 weeks were divided into healthy control group, CUMS model group, CUMS combined with 10 mg/kg FMN group, CUMS combined with 20 mg/kg FMN group and CUMS combined with 1.8 mg/kg fluoxetine hydrochloride (Flu) group. Except for healthy control group, other groups were stimulated with CUMS and administered drugs for 28 days. Sugar water preference, forced swimming experiment and open field experiment were used to observe the emotional behavior of rats in each group. HE staining was used to observe the pathological injury degree of brain equine area. The contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected by the kit. The apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) in the brain tissue. The levels of tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin 6 (IL-6) in peripheral blood were measured by ELISA. Western blot analysis was used to detect Bcl2, Bcl2 associated X protein (BAX), cleaved caspase-9, cleaved caspase-3, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and phosphorylated nuclear factor κB p65 (p-NF-κB p65) in brain tissues. Results Compared with CUMS model group, sugar water consumption, open field activity time, open field travel distance and swimming activity time significantly increased in the CUMS combined with 20 mg/kg FMN group and the CUMS combined with 1.8 mg/kg Flu group. The number of new outarm entry increased significantly, while the number of initial arm entry and other arm entry decreased significantly. The pathological damage of brain equine area was alleviated, and the contents of 5-HT and 5-HIAA were significantly increased. The ratio of BAX/Bcl2 and the expression of cleaved caspase-9 and cleaved caspase-3 protein as well as the number of apoptotic cells were significantly decreased. The contents of TNF-α, iNOS and IL-6 were significantly decreased. The protein levels of TLR4, MyD88 and p-NF-κB p65 were significantly decreased. Conclusion FMN can inhibit the release of inflammatory factors by blocking NF-κB pathway and improve cognitive and behavioral ability of CUMS aged rats.
Rats ; Animals ; Horses ; NF-kappa B/metabolism* ; Signal Transduction ; bcl-2-Associated X Protein/metabolism* ; Toll-Like Receptor 4/metabolism* ; Caspase 3/metabolism* ; Caspase 9/metabolism* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Myeloid Differentiation Factor 88 ; Hydroxyindoleacetic Acid/pharmacology* ; Serotonin/metabolism* ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Cognition

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
3,4-Dihydroxyphenylacetic Acid/pharmacology* ; Animals ; Antidepressive Agents/therapeutic use* ; Chromatography, Liquid ; Depression/drug therapy* ; Disease Models, Animal ; Dopamine ; Eosine Yellowish-(YS)/pharmacology* ; Hematoxylin/pharmacology* ; Hippocampus/metabolism* ; Homovanillic Acid/pharmacology* ; Hydroxyindoleacetic Acid/metabolism* ; Methoxyhydroxyphenylglycol/pharmacology* ; Monoamine Oxidase/metabolism* ; Neurotransmitter Agents/metabolism* ; Norepinephrine/pharmacology* ; Plant Extracts ; Rats ; Rehmannia/chemistry* ; Serotonin/metabolism* ; Serotonin Plasma Membrane Transport Proteins/pharmacology* ; Stress, Psychological/metabolism* ; Tandem Mass Spectrometry ; Tryptophan Hydroxylase/metabolism*

This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and 100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography (HPLC) and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group (P<0.05, P<0.01). As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group (P<0.05), but opposite presentations were noted in the colon (P<0.05). As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantly but obviously increased in the colon (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon (P<0.05); besides, they significantly reverse the synaptophysin level in the hippocampus and colon (P<0.05). The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.
Alkaloids ; isolation & purification ; pharmacology ; Animals ; Benzodioxoles ; isolation & purification ; pharmacology ; Colon ; metabolism ; Hippocampus ; metabolism ; Hydroxyindoleacetic Acid ; metabolism ; Irritable Bowel Syndrome ; metabolism ; physiopathology ; Male ; Motor Activity ; drug effects ; Piper nigrum ; chemistry ; Piperidines ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Polyunsaturated Alkamides ; isolation & purification ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo investigate the mechanism of iridoid from Valeriana jatamansi treating irritable bowel syndrome.

METHODSixty male SD rats were equally divided into 6 groups (2 controls, 1 model and 3 treatment doses) with 10 rats per group. The test groups were administered with iridoid (24.92, 12.46, 6. 23 mg x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x kg(-1), positive control) or distilled water (negative control). The model was established by chronic stress and independent feeding. The influence of iridoid from V. jatamansi on 5-HT and 5-HIAA in colon, serum and hypothalamic were observed in all groups.

RESULTIn the model group, the content of 5-HT in colon and serum increased significantly, but the content of 5-HT in hypothalamic decreased significantly. The content of 5-HIAA and the value of 5-HT/5-HIAA had no significant change. In three iridoid-treated groups, the content of 5-HT in colon and serum decreased, but the content of 5-HT in hypothalamic increased. The content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon and serum reduced.

CONCLUSIONThe mechanism of iridoid from V. jatamansi treating irritable bowel syndrome may be related to the regulation effect to the levels of 5-HT from Gastrointestinal to central nervous system.

Animals ; Chromatography, High Pressure Liquid ; Colon ; drug effects ; metabolism ; Hydroxyindoleacetic Acid ; blood ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Iridoids ; therapeutic use ; Irritable Bowel Syndrome ; blood ; drug therapy ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Serotonin ; blood ; metabolism ; Valerian ; chemistry

OBJECTIVETo observe the effect of Chinese herbal compound on variance of neurotransmitters in rat telencephalon and to further discuss the mechanism underlying Chinese herbal compound in improving exercise capacity and promoting recovery from exercise-induced fatigue.

METHODS64 rats (8 week old) were randomly divided into medicine group (MG) and control group (CG). Chinese herbal compound was administered to rats of MG for 8 weeks. 8 weeks later, every group was divided into 4 subgroups and all were killed at different time point separately, and then neurotransmitter in rat brain was tested.

RESULTSThe exhaustion time of MG was significantly longer than that in CG (P < 0.01). In rest conditions, glutamic acid (GLU) of MG was significantly higher than that in CG (P < 0.01), while, there were no significant differences between MG and CG in other indexes. After fixed quantitative load exercise, the content of 5-hydroxytryptamineZZ(5-HT), 5-hydroindole acetic (5-HIAA), gamma-aminobutyric acid (GABA), Dopamine (DA) and 5-HT/5-HIAA were significantly lower than those in CG, while, GLU, GLU/GABA and DA/5-HT were significantly higher than those in CG. Compared with CG, exhaustion significantly (P < 0.05) decreased 5-HT, GABA and 5-HT/5-HIAA, and significantly (P<0.05) increased GLU, DA/5-HT and GLU/GABA level in MG. 12 h after exhaustion, in contrast to CG, level of 5-HT and 5-HT/5-HIAA in MG were significantly (P < 0.01) lower while GLU, DA, GABA and DA/5-HT were significantly (P < 0.01) higher.

CONCLUSIONDuring exhaustion exercise, Chinese herbal compound demonstrated strong inhibiting effect on synthesis of 5-HT, 5-HIAA, DA, GABA and promoting effect on GLU synthesis, this had been confirmed by the combined effect, including increase of excitatory transmitter and excitability of central nervous system and the prolongation of exhaustion time and promoting recovery from fatigue.

Amino Acids ; metabolism ; Animals ; Biogenic Monoamines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Fatigue ; metabolism ; physiopathology ; Hydroxyindoleacetic Acid ; metabolism ; Male ; Neurons ; metabolism ; Physical Conditioning, Animal ; physiology ; Physical Exertion ; physiology ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Telencephalon ; drug effects ; metabolism

The relationship between omega-3 polyunsaturated fatty acids (PUFAs) and violent-aggressive behavior has been payed attention since 1980s. Their correlation was explored by many epidemiological investigations, and the effect of PUFAs on prevention or reduction of violent-aggressive behavior in different groups were also affirmed by some intervention studies. This article summarized the previous studies and reviewed the history of epidemiological or intervention studies on PUFAs and its relationship with violent-aggressive behavior. It also presented the possible influencing factors in these studies and possible mechanisms.
Aggression ; Animals ; Dietary Fats, Unsaturated/pharmacology* ; Dietary Supplements ; Docosahexaenoic Acids/pharmacology* ; Eicosapentaenoic Acid/pharmacology* ; Fatty Acids, Omega-3/pharmacology* ; Fatty Acids, Omega-6/pharmacology* ; Fishes ; Folic Acid/metabolism* ; Humans ; Hydroxyindoleacetic Acid/metabolism* ; Norepinephrine/metabolism* ; Risk Factors ; Serotonin/metabolism* ; Violence/prevention & control*

OBJECTIVE: This study investigates the effects of chronic alcohol exposure on rat brain THmRNA expression, TH (tyrosine hydroxylase) acitivity, and TPH (tryptophan hydroxylase) activity which are important in synthesis of dopamine and serotonin and other components of both the dopaminergic and serotonergic systems of the rat brain. METHODS: Rats were fed a liquid diet containing alcohol for 4 weeks. We investigated effects of chronic alcohol exposure on dopaminergic systems as follows. We evaluated expression of THmRNA in LC, VTA and substantia nigra by using in-situ hybridization and measured activity of TH by using immunoassay. We used HPLC for simultaneous measurement of dopamine, DOPAC and HVA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. Also we investigated serotonergic systems as follows. We evaluated expression of TH mRNA in the dorsal raphe nucleus by using radioprobe and measured the activity of TPH by using enzyme immunoassay. We used HPLC for simultaneous measurement of 5-HT and 5-HIAA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. RESULTS: Alcohol exposure for 4 weeks increased the expression of TH mRNA in the ventral tegmental area and the locus ceruleus but not in the substantia nigra. The 4 weeks of alcohol exposure did not cause significant changes in levels of dopamine and metabolites in the different areas of the brain, nor was it associated with changes in the maximal binding and affinity (Kd) of anterior striatal dopamine D2 receptor. Alcohol exposure for 4 weeks had no effect on the expression of TPH mRNA or on the activity of TPH in the dorsal raphe nucleus and the hypothalamus. CONCLUSION: We reported at first that chronic alcohol exposure could increase TH mRNA in the locus ceruleus. In a previous study of acute alcohol treatment, there is increase of dopamine metabolism but in this study, we did not observe any changes in dopamine metabolism in the different areas of the brain. Also we did not see any significant changes in the synthesis and metabolism of serotonin after 4 weeks of chronic alcohol exposure compared with control. Therefore, synthesis and metabolism of serotonin was affected in the acute phase. And, as previous reports have suggested, any changes caused by alcohol returned to previous levels via adaptation and regulatory mechanisms.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Chromatography, High Pressure Liquid ; Diet ; Dopamine ; Hippocampus ; Hydroxyindoleacetic Acid ; Hypothalamus ; Immunoassay ; Immunoenzyme Techniques ; Locus Coeruleus ; Metabolism ; Raphe Nuclei ; Rats* ; Receptors, Dopamine D2 ; Rhombencephalon ; RNA, Messenger ; Serotonin ; Substantia Nigra ; Synaptic Transmission* ; Ventral Tegmental Area

OBJECTIVE: The aim of the this study was to compare the effects of clonidine (a alpha2-adrenoceptor and imidazoline receptor agonist), yohimbine (a selective alpha2-adrenoceptor antagonist) and idazoxan (a alpha2-adrenoceptor and imidazoline receptor antagonist) on extracellular monoamines and their metabolites by using the awakening animal microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in brain regions, which are suggested to have regulatory role in depression. METHODS: We used intracerebral microdialysis in awakening rats by inserting probe through the dorsal hippocampus and occipital cortex especially in primary visual cortex, We studied respective effects of 2.0 mg/kg of clonidine, 5.0 mg/kg of yohimbine, and 5.0 mg/kg of idazoxan on the release of MHPG (a major metabolite of norepinephrine), norepinephrine (NE), DOPAC (a major metabolite of dopamine), and 5-HIAA (a main metabolite of serotonin) by intraperitoneal administration. RESULTS: Clonidine decreased the release of MHPG, NE, DOPAC, and 5-HIAA in both dorsal hippocampus and occipital cortex regions, and there were no significant differences in releasing pattern of all monoamines and their metabolites. Both yohimbine and idazoxan enhanced the release of MHPG, NE, DOPAC, and 5-HIAA in both brain regions, but there were significant differences in releasing pattern of NE and 5-HIAA. Idazoxan induced the delayed and higher efflux of NE and 5-HIAA in the primary visual cortex than yohimbine, but not in the hippocampus. CONCLUSION: This study shows that the selective alpha2-adrenoceptor antagonists increase basal monoamine output and enhance the metabolism of them in the hippocampus and primary visual cortex, and the imidazoline receptor has modulatory role in the regulation of monoamine release in primary visual cortex than hippocampus. It also suggests that high turnover rate of serotonin and norepinephrine in primary visual cortex may contribute to the pathophysiological role in depression.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain ; Chromatography, Liquid ; Clonidine ; Depression ; Hippocampus* ; Hydroxyindoleacetic Acid ; Idazoxan ; Metabolism ; Methoxyhydroxyphenylglycol ; Microdialysis ; Norepinephrine ; Rats* ; Serotonin ; Visual Cortex* ; Yohimbine

PURPOSE: We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. METHODS: The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indoleacetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. RESULTS: The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease(23.0+/-4.2%, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation(120.8+/-54.9%, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia(35.3+/-7.6% of basal level, P<0.05) and reoxygenation (105.8+/-32.3%). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased(74.9+/-3.1%) and increased(118.1+/-7.8%) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). CONCLUSION: Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Anoxia ; Brain* ; Carotid Artery, Common ; Cerebrospinal Fluid ; Dopamine ; Humans ; Hydroxyindoleacetic Acid ; Infant, Newborn ; Metabolism* ; Microdialysis ; Rats*

The remarkable change of phenomenon induced by stress increase energy metabolism that can induce many reactive oxygen species (ROS) production. ROS can peroxidize cellular macromolecules including lipid and protein. The object of this study was to investigate whether stress may induce cellular damage by producing ROS and whether vitamin E, as a strong lipid-soluble antioxidant, can protect cells against reactive oxygen species produced by noise and immobilization stress in SD rats. The stress group increased 5-hydroxyindole aceti acid (5-HIAA) , one of the stress hormone, in brain tissue and free fatty acid in plasma. Vitamin I treatment had no effect on 5-HIAA but free fatty acid contents decreased with a fortified vitamin I diet. Furthermore, the body weight of vitamin I-treated rats increased more than that of the stress group. Lipid peroxidation and protein degradation as an index of oxidative damage in brain tissue decreased with the use of the fortified vitamin I diet supplement. The results suggest that vitamin I supplements have a protective effect against noise and immobilization stress-induced oxidative damage in brain tissue.
Animals ; Antigens, CD59* ; Body Weight ; Brain* ; Diet ; Energy Metabolism ; Hydroxyindoleacetic Acid ; Immobilization* ; Lipid Peroxidation ; Noise ; Plasma ; Proteolysis ; Rats* ; Reactive Oxygen Species ; Vitamin E* ; Vitamins*