Neurotransmission In Rats Research Articles

Fustin, a Potent Phytochemical, Attenuates Scopolamine-induced Memory Impairment and Neurodegeneration by Modulating Neuroinflammation and Neurotransmitters.

Fustin, a photogenic flavanol found in the plant Rhus verniciflua Stokes, has been involved in multiple disease ailments and has a beneficial pharmacological effect and a history of use in traditional medicine. The present research aimed to study the impact of fustin on scopolamine (SCOP)-induced memory impairment and neurodegeneration by modulating neuroinflammation and neurotransmitters in rats. A total of 30 healthy Wistar rats were allocated into five groups (n=6). Group I- served as control and received saline solution (1mL/kg i.p.), group -II- fustin (100 mg/kg, orally), group -III -SCOP (1 mg/kg, i.p.), and group -IV and V were given fustin (50 and 100 mg/kg/p.o.) with SCOP (1 mg/kg, i.p.) for 14-days. After 14 days, 2 hours after SCOP injection, the Y-maze and Morris water maze (MWM) tests were performed. After behavioral tests rats were subsequently euthanized, and brain supernatants were used to estimate choline-acetyltransferase (ChAT), acetylcholinesterase (AChE), antioxidant [superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)], and total protein, oxidative stress markers [nitrate and malondialdehyde (MDA)], pro-inflammatory markers [tumor necrosis factor (TNF-α), and Interleukins-1β (IL-1β) and IL-6]. Also, neurotransmitters such as serotonin (5-HT), dopamine (DA), ϒ-amino butyric acid (GABA), acetylcholine (Ach), and noradrenaline (NA) contents were performed. Fustin exhibited substantial behavioral improvement in the Y-maze measures spontaneous alterations percentage (SA%) and decreased latency time following the acquisition and prolonged time spent in the probe trial in the MWM test. Moreover, fustin inhibits enhanced neuroinflammatory cytokines and oxidative stress markers and improves the neurotransmitters. The findings of this study suggest that fustin inhibits SCOP impact on cognitive abilities in rats. The present investigation demonstrates that fustin, a potent phytochemical, effectively mitigated the behavioral and physiological changes induced by SCOP in rats. This was primarily achieved by modulating the levels of inflammatory response and neurotransmitters.

Toxoplasma gondii induced cognitive impairment in rats via dysregulation of dopamine receptors and indoleamine 2,3 dioxygenase

Toxoplasma gondii (T. gondii) is a parasite capable of residing in the brain of their host which influences behaviour changes due to alterations in the neurotransmitters. Consequently, dopamine receptors (DRD) and indoleamine 2, 3 dioxygenase (IDO) dysregulation facilitate the progression of behaviour changes in a host as a response to infection. This study tested the effect of neurotransmitter changes as a result of T. gondii infection on rats cognitive impairment. The T. gondii strain of type I, II and III from Malaysia were previously identified by standard procedures. Sporulated oocysts each of type I, II and III were inoculated separately into three groups of Wistar rats (n = 9) respectively. Two separate control groups received either phosphate buffered saline (PBS) or MK-801 (dizocilpine). Behaviour changes were evaluated at nine weeks post infection in a square box, elevated plus maze and gene expression level of DRD and IDO compounds. The study revealed increased fatal feline attraction, reduced anxiety, decreased DRD and increased IDO gene expression in the T. gondii infected groups and MK-801 compared to the PBS control group. In conclusion, T. gondii infection alter the level of neurotransmitters in rat which cause cognitive impairment. This implies that all the T. gondii strain can cause behaviour changes if human were infected.

Free-L-Cysteine improves corticosterone-induced behavioral deficits, oxidative stress and neurotransmission in rats.

L-Cysteine (L-Cys) is a semi-essential amino acid. It serves as a substrate for enzyme cystathionine-β-synthase in the central nervous system (CNS). L-Cys showed various antioxidant characteristics. Though, studies on the effect of free L-Cys administration to evaluate the CNS functioning is very limited. Therefore, we assessed the effects of L-Cys on corticosterone (CORT) induced oxidative stress, behavioral deficits and memory impairment in male rats. L-Cys (150mg/kg/ml) administered to vehicle and CORT (20mg/kg/ml) treated rats orally for 28days. Behavioral activities were conducted after treatment period. Subsequently, rats were sacrificed, blood and brain were removed. Hippocampus was isolated from brain and then hippocampus and plasma were collected for oxidative, biochemical and neurochemical analysis. Results showed that repeated treatment of L-Cys produced antidepressant, anxiolytic and memory-improving effects which may be ascribed to the enhanced antioxidant profile, normalized cholinergic, serotonergic neurotransmission in brain (hippocampus) following CORT administration. Increased plasma CORT by CORT administration was also normalized by L-Cys. The current study concluded that administration of free L-Cys improved the behavioral, biochemical, neurochemical and redox status of CNS. Hence, L-Cys could be protective therapeutic modulator against stress induced neurological ailments.

Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain

Abstract In this study, the neuroprotective potential of either Pergularia tomentosa leaf methanolic extract (PtE) alone or in combination with selenium nanoparticles (SeNPs-PtE) was investigated against lead acetate (PbAc)-induced neurotoxicity. Experimental rats were pretreated with PtE (100 mg/kg) or SeNPs-PtE (0.5 mg/kg) and injected intraperitoneally with PbAc (20 mg/kg) for 2 weeks. Notably, SeNPs-PtE decreased brain Pb accumulation and enhanced the level of dopamine and the activity of AChE compared to the control rats. In addition, elevated neural levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione along with decreased lipid peroxidation levels were noticed in pretreated groups with SeNPs-PtE. Moreover, SeNPs-PtE significantly suppressed neural inflammation, as indicated by lower levels of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, nuclear factor-kappa B p65, and nitric oxide in the examined brain tissue. The molecular results also unveiled significant down-regulation in iNOS gene expression in the brains of SeNPs-PtE-treated rats. In addition, SeNPs-PtE administration counteracted the neural loss by increasing B-cell lymphoma 2 (Bcl-2) and brain-derived neurotrophic factor levels as well as decreasing BCL2-associated X protein and caspase-3 levels. To sum up, our data suggest that P. tomentosa extract alone or in combination with SeNPs has great potential in reversing the neural tissue impairment induced by PbAc via its antioxidant, anti-inflammatory, and anti-apoptotic activities. This study might have therapeutic implications in preventing and treating several lead-induced neurological disorders.

LC-MS/MS combined with blood-brain dual channel microdialysis for simultaneous determination of active components of astragali radix-safflower combination and neurotransmitters in rats with cerebral ischemia reperfusion injury: Application in pharmacokinetic and pharmacodynamic study

BackgroundAstragali Radix-Safflower combination (ARSC) is widely utilized in clinic to treat cerebral ischemia/reperfusion injury (CI/RI). Whereas, there is no in-depth research of the pharmacokinetics (PK) and pharmacodynamics (PD) analysis of ARSC after intragastric administration in rats with CI/RI. PurposeThe purpose of this research is to investigate the PK characteristics of eight active ingredients (astragaloside IV, calycosin, calycosin-7-O-β-glucoside, formononetin, ononin, hydroxysafflor yellow A, syringin and vernine) of ARSC, and the regulation of neurotransmitters disorders, revealing the pharmacodynamic substance basis and the mechanism of ARSC in treating CI/RI from the molecular level. MethodsWe established a new method which based on blood-brain dual channel microdialysis (MD) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to continuously gather, and determine the components of ARSC and neurotransmitters related to CI/RI in vivo. The collected data were analyzed by sigmoid-Emax function. The neurotransmitters primarily regulated in CI/RI rat were discussed by principal component analysis and the compound most associated with total pharmacodynamics was chosen by partial least squares regression. ResultsThe validated LC-MS/MS method had specificity and selectivity to simultaneously analyze the concentration of eight active components of ARSC extract and five neurotransmitters of CI/RI rats. The recovery rates of brain MD probe and blood MD probe were stable within six hours. The MD probes recovery rates decreased with the increase of flow rates, but the solution concentration had little effect on the probes recovery rates. It was feasible to correct the recovery rates of probes in vivo by using reverse dialysis method. All eight active ingredients of ARSC could pass across the blood brain barrier after CI/RI. ARSC regulated the release of glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT) and aspartic acid (Asp). Notably, astragaloside IV and hydroxysafflor yellow A might have better regulatory effect on neurotransmitters in comparison with other six measured components of ARSC, and Glu was the neurotransmitter mainly regulated in CI/RI rats. ConclusionThe ARSC was able to treat CI/RI through ameliorating neurotransmitters disorders. There was a hysteresis between the peaked drug concentration and maximum therapeutic effect of ARSC. The drug effective concentrations range of ASIV, calycosin, calycosin-7-O-β-glucoside, syringin and vernine in blood microdialysate and calycosin, syringin, vernine in brain microdialysate were narrow, which need be paid attention in clinical use.

Design, characterization of Resveratrol-Thermosensitive Hydrogel System (Res-THS) and evaluation of its anti-depressant effect via intranasal administration

Thermosensitive Hydrogel System (THS) is a suitable candidate for targeted drug delivery, because of its intelligent response and controlled release. In this work, combination of guanidine-chitosan (GCS), β-glycerol phosphate disodium salt (β-GP) and hydroxypropyl-β-cyclodextrin (HP-β-CD) can successfully result in a novel THS by single factor and response surface method. The characterization of THS is detected with gelation temperature, FT-IR, SEM, in vitro release, rheology and biocompatibility. Resveratrol (Res) is selected as a model drug to evaluate the anti-depressant effects of THS loaded Res (Res-THS) via intranasal administration of chronic unpredictable mild stress (CUMS) rats. The results display that the Res-THS can increase concentration of neurotransmitter in rats’ brain tissue via intranasal administration, indicating the anti-depressant effect.

Serotonin Discharge Regulation by Additional Neurotransmitters of Rat Hippocampus Associated With the Continence Central Circuit.

PurposeThe lower urinary tract is believed to be centrally regulated with the involvement of a range of neurotransmitters. The parasympathetic excitatory input to the urinary bladder is suppressed when the serotonergic system is activated, and thereby voiding is blocked. In healthy people, continence is usually underpinned by hippocampal formation (circuit 3). In order to advance knowledge of how serotoninergic neurons and additional nerve fibers were correlated, the purpose of the present work was to research how the discharge of serotonin from hippocampal slices was affected by different neurotransmitters in rat models.MethodsThe adopted procedure involved administration of the central neurotransmitters acetylcholine, norepinephrine, dopamine, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), glycine, and neuropeptide Y as well as monitoring of the alterations in the discharge of [3H]5-hydroxytryptamine (5-HT). Furthermore, to determine whether the effect of the neurotransmitters was influenced by interneuron, tetrodotoxin was also employed.ResultsAcetylcholine (10-5M) did not alter [3H]5-HT discharge, whereas more 5-HT was discharged from the hippocampal slices of rats under stimulation by norepinephrine (10-5M) as well as dopamine (10-5M) and tetrodotoxin (10-6M) did not inhibit the discharge. By contrast, tetrodotoxin inhibited the discharge of [3H]5-HT that was exacerbated by NMDA (10-4M). Meanwhile, compared to control, GABA (10-5M), glycine (10-5M), or neuropeptide Y (10-6M) did not alter the [³H]5-HT discharge.ConclusionsFrom the research findings, it can be concluded that 5-HT discharge from rat hippocampus is enhanced by norepinephrine and dopamine through direct effect on the 5-HT neuronal terminal. By contrast, 5-HT discharge is intensified by NMDA by activating interneurons.

Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats.

Acute neurotoxicity of Semen Strychni can result in sudden death in epilepsy. The detoxification method and mechanism of Semen Strychni acute poisoning have not been clarified. This experiment focused on the mechanism of Semen Strychni neurotoxicity and the alleviation effects of isoliquiritigenin. The rats were intraperitoneally injected with Semen Strychni extract (125 mg/kg), followed by oral administration of isoliquiritigenin (50 mg/kg) for 7 days. FJ-B staining was used to evaluate the degree of injury on hippocampus neurons. The concentration of monoamines, amino acids, and choline neurotransmitters, the Dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolic pathway in the hippocampus, cerebellum, striatum, prefrontal cortex, hypothalamus, serum, and plasma were detected by LC-MS/MS. The expression of neurotransmitter metabolic enzymes [catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)] and neurotransmitter receptors [glutamate N-methyl-D-aspartic acid receptors (NMDARs) and gamma-aminobutyric acid type A receptor (GABRs)] were, respectively determined using ELISA and qRT-PCR. The results indicated that Semen Strychni induced neuronal degeneration in the hippocampal CA1 region. Meanwhile, Semen Strychni inhibited the mRNA expression of NMDAR1, NMDAR2A, NMDAR2B, GABRa1, GABRb2 and reduced the level of MAO, which disrupted the DA and 5-HT metabolic pathway. However, isoliquiritigenin reversed these effects. In summary, isoliquiritigenin showed alleviation effects on Semen Strychni-induced neurotoxicity, which could be attributed to restoring neurotransmitters metabolic pathway, most likely through the activation of NMDA receptors.

Functional Assessment of Peripheral Cholinergic Neurotransmission in Rats with Fetal Valproate Syndrome

Functional Assessment of Peripheral Cholinergic Neurotransmission in Rats with Fetal Valproate Syndrome

Association of Peripheral Plasma Neurotransmitters with Cognitive Performance in Chronic High-altitude Exposure

Long-term living at high altitude causes significant impairment of cognitive function. Central neurotransmitters are potential mediators of cognitive performance. We aimed to determine whether there were significant associations between select peripheral plasma neurotransmitters and cognitive performance in humans with chronic high-altitude (HA) exposure and to determine the association between peripheral plasma neurotransmitters and brain neurotransmitters in rats after chronic hypobaric hypoxia (HH) exposure. We demonstrated that 3,4-dihydroxy-L-phenylalanine (DOPA), dopamine, serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA) and GABA in the peripheral plasma were associated with cognitive performance in humans with HA exposure. Consistent with this result, peripheral plasma DOPA, dopamine, serotonin, 5-HIAA and glutamate were associated with brain neurotransmitter levels after chronic HH exposure in rats. These results provide experimental data indicating that neurotransmitter levels and cognitive performance are modified in chronic high-altitude exposure, with a possible causal effect.

Simultaneous determination of five amino acid neurotransmitters in rat and porcine blood and brain by two-dimensional liquid chromatography

A method for the simultaneous determination of aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in animal blood and brain by two-dimensional liquid chromatography (2D-LC) combined with ultraviolet detection was established for the first time. First, the amino acid neurotransmitters (AANTs) were labeled on the corresponding fluorescent derivatives with 4-fluoro-7-nitrobenzofurazan (NBD-F), enriched on the extraction column and automatically transferred to the analytical column to achieve on-line extraction and complete separation of the target components. This method exhibited good selectivity, and the correlation coefficients for the analyte calibration curves of were > 0.99. The intra- and inter-day precisions were ≤ 16.03, and the accuracies were in the range of 70.59–116.20%. The system realizes the rapid detection and stability quantification of the five AANTs, which proves that the alternative dilution method is feasible. The results show that the system has high loading capacity, excellent resolution, and good peak shape and is not affected by other endogenous substances. Moreover, the developed method has been successfully applied to the analysis of biological samples in the blood and whole brain of rats and pigs. The content of AANTs in the hippocampus and cortex of rats was higher than that in those of pigs. This method is expected to provide applicability for the determination of AANTs in pharmacological, pharmaceutical and clinical research in nervous science.

Effects of Ganmai Dazao Tang on synaptic structure of hippocampal neurons in depression model rats

Objective: To investigate the effects of Ganmai Dazao Tang on behavior and monoamine neurotransmitters in rats with depression, and to explore its potential mechanism from synaptic structure. Methods: Sixty SD rats were randomly divided into 5 groups: normal control group, model group, fluoxetine group (10.8 mg/kg), Ganmai Dazao Tang high and low dose group (9.72, 4.86 g/kg), 12 rats in each group. Except the control group, the rats in the other groups were all chronically unpredictable mild stress (CUMS) to establish a depression model, and were treated by intragastric administration for 21 days. The depression-like behaviors of rats were evaluated by sucrose consumption test and open field test. The contents of serotonin (5-HT) and norepinephrine (NE) in hippocampus were detected by ELISA. The synaptic damage of neurons was observed by Golgi staining. The synaptic structure protein expression levels of MAP-2 and GAP-43 of hippocampus were detected by Immunohistochemistry and Western blot. Results: Compared with control group, the sucrose preference and autonomic activity scores of the depression model rats were decreased significantly (P＜0.01), the levels of 5-HT and NE in hippocampus were decreased significantly (P＜0.01), and the dendritic spines were absent, and the expressions of MAP-2 and GAP-43 were down-regulated significantly (P＜0.01). After treated with Ganmai Dazao Tang, the depression-like behavior of the model rats was significantly relieved (P＜0.01), and the levels of 5-HT and NE were increased (P＜ 0.05). Dendritic spine density, length and branching were increased, the expressions of MAP-2 and GAP-43 were increased (P＜ 0.01). Conclusion: Ganmai Dazao Tang can improve the depression-like behavior of depression model rats and increase the monoamine neurotransmitter content in hippocampus, which may be related to up-regulation of synaptic structural proteins and relief of synaptic damage in neurons.

The interaction effect of abamectin and tramadol on brain neurotransmitters in rats

A single -oral dose of abamectin (10 mg/Kg body weight; LD50) and tramadol dose of 40 mg kg-1 was given orally by gavage to the rats and the brain samples were examined biologically and histopathologically at various times (0.5, 1, 1.5, 2, 2.5, 3, 3.5 and 24 h) after dosing. Results revealed that oxidative stress was noticed, since it provokes a significant in brain due to insecticides administration. A significant reduction in, acetylcholinesterase (AchE), Nor-epinephrine (NE), serotonin (5-HT), epinephrine (E) and dopamine (DA) in treated group as compared to control group (P< 0.05). We found that there were neurotoxic effects of pesticides such as abamectin on brain activities, neurotransmitters and alterations in brain tissue. Tramadol, abamectin alone or in combination produced a significant increase in AchE of the brain of treated rats. In normal brain, the activity of acetylcholine esterase, is necessary for the healthy function of the brain, and changes in AchE activity are accompanied by clear signs of neurotoxicity. The central cholinergic neurotransmission in the brain is a crucial factor in cognitive functions including memory and learning

The interaction effect of abamectin and tramadol on brain neurotransmitters in rats

The interaction effect of abamectin and tramadol on brain neurotransmitters in rats

N-3 PUFA Have Antidepressant-like Effects Via Improvement of the HPA-Axis and Neurotransmission in Rats Exposed to Combined Stress.

Early life and adulthood stress increase vulnerability for mental illness, and eventually trigger depression. N-3 polyunsaturated fatty acids (PUFA) have antidepressant effects, but their effect on rats exposed to combined stress has been not investigated. This study aimed to investigate whether n-3 PUFA supplementation had antidepressant-like effects in rat models of depression induced by a combination of chronic mild stress (CMS) and maternal separation (MS) through the modulation of the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmission. Rats were fed the n-3 PUFA diet during the pre-weaning or post-weaning period or for lifetime, and allocated to different groups based on the type of induced stress: non-stress (NS), CMS + MS, or CMS alone. N-3 PUFA improved the depressive behaviors of the CMS alone and CMS + MS groups and modulated the HPA-axis by reducing the circulating adrenocorticotropic hormone, corticosterone, and corticotropin-releasing factor expression, and increasing glucocorticoid receptor expression. N-3 PUFA also modulated brain phospholipid fatty acid concentration, thus reducing inflammatory cytokines; improved the serotonergic pathway, thus increasing the expression of the brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), serotonin-1A receptor, and serum levels of serotonin; but did not affect glutamatergic neurotransmission. Furthermore, n-3 PUFA decreased the hippocampal expression of microRNA-218 and -132, increased that of microRNA-155, and its lifetime supplementation was more beneficial than pre- or post-weaning supplementation. This study suggests that n-3 PUFA has an antidepressant effect in rats exposed to combined stress, through the improvement of the HPA-axis abnormalities, the BDNF-serotonergic pathway, and the modulation of microRNAs.

Effect of Jian-Pi-Zhi-Dong Decoction on the Amino Acid Neurotransmitters in a Rat Model of Tourette Syndrome and Comorbid Anxiety Disorder.

Amino acid neurotransmitters have been shown to correlate with Tourette syndrome (TS) and its comorbidities. In this study, we investigated the effects of Jian-Pi-Zhi-Dong Decoction (JPZDD), a formula containing 10 different Chinese medical herbs, on amino acid neurotransmitters in rats. We established a rat model of Tourette syndrome and comorbid anxiety with an iminodipropionitrile injection plus uncertain empty water bottle stimulation for 3 weeks. Then the rats were randomly divided into four groups: control group and model group were gavaged with saline, while the remaining two treatment groups were gavaged with fluoxetine hydrochloride or JPZDD for four consecutive weeks. We recorded the behaviors of the rats with TS and comorbid anxiety by stereotypy recording, open field test, and elevated plus maze. We observed mitochondrial changes with transmission electron microscopy. We measured the content of glutamate (GLU) and γ-aminobutyric acid (GABA) both in the serum and striatum and the expression of their receptors by Western blot and real-time polymerase chain reaction. The study revealed that JPZDD was effective in alleviating the behavioral symptoms of both tic and anxiety in the rat model groups. These results might be associated with the increase in GABA levels and decrease in GLU levels in the serum, as well as an increase in striatal GABA level by the activation of GABA receptors Type A (GABAAR). JPZDD treatment also reversed the mitochondrial dysfunction both in the striatum and cortex in affected animals.

Regulatory effect of Jiaotai Pills on central and peripheral neurotransmitters in rats with heart-kidney imbalance insomnia

To explore the pathogenesis of heart and kidney imbalance insomnia and the regulatory effect of Jiaotai Pills, in order to study the changes of central and peripheral neurotransmitters in rat. Insomnia rats with heart and kidney imbalance were induced through intraperitoneal injection with p-chlorophenylalanine(PCPA, 400 mg·kg~(-1)·d~(-1)), and the model rats were intragastrically administrated with Jiaotai Pills(3.3 g·kg~(-1)·d~(-1)) for 7 days. Nine neurotransmitters were determined by UPLC-MS/MS and principal component analysis(PCA) method in serum, urine, brain, heart, liver, kidney and adrenal gland of rats. The results showed that the ratio of 5-HT and 5-HIAA in platelet of insomnia rats was significantly lower than that in the normal group, and Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, the changed neurotransmitters in blood of insomnia rats were 5-HIAA, E, NE, DA, Glu and ACH, and except ACH, the changes of 7 kinds of neurotransmitters in urine were more significant, Jiaotai Pills had a significant up-regulatory or down-regulatory effect. Compared with the normal group, all of the 8 neurotransmitters in insomnia rats except HVA were changed. Jiaotai Pills could regulate the neurotransmitters in each tissue of insomnia rats, especially in brain, liver and adrenal gland. In conclusion, insomnia is caused by not only a change of neurotransmitters in brain, but also a series of changes in peripheral tissues. It indicates that insomnia is a systematic imbalance of neurotransmitters. Jiaotai Pills not only regulates the central nervous system, but also has a certain protective effect on other organs, reflecting the multi-target and systematic effect of Jiaotai Pills in the treatment of insomnia.

Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling.

Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.

Transplantation of NSCs Promotes the Recovery of Cognitive Functions by Regulating Neurotransmitters in Rats with Traumatic Brain Injury.

Transplantation of neural stem cells (NSCs) may be a potential strategy for traumatic brain injury treatment (TBI) due to their intrinsic advantages, such as cell replacement, secretion of neurotrophins and formation of functional synapses with host. However the underlying effects of transplanted NSCs on host micro-environment still need to be further elucidated. In this manuscript the effects of NSCs on release of neurotransmitter, survival of hippocampal neurons, reactivity of astrocytes and recovery of cognitive function after TBI were observed. The NSCs were isolated from cortex of neonatal Sprague-Dawley rat and then transplanted into injured brain regions caused by free-weight drop. The proliferation of astrocytes around injured sites were examined by GFAP immunofluorescent staining on 3, 7, 14days after injury. The survival of neurons at CA1 regions of hippocampus toward contused regions was observed by HE staining on 3 and 14days post-injury. The content of glutamic acid (Glu) and GABA in hippocampal tissues was examined on 1, 3, 7, 14, 28days after injury by ELISA. On third day post-injury, hippocampal-dependent spatial memory was measured for 5days without intermittent. NSCs in culture have the ability to proliferate and differentiate into different phenotypes of neural cells. After transplantation of NSCs, the proliferation of astrocytes around injured site was significantly inhibited compared to the injured group. At the same time the survival of neurons in hippocampal CA1 region were much more than those in injured group on 14days post-injury. Meanwhile, the cognitive functions in NSC transplanted group was remarkably improved compared with injured group (p < 0.05). Furthermore, NSCs transplantation dramatically inhibited the release of Glu and maintained the content of GABA in injured hippocampal tissues on 1, 3, 7, 14, 28days post-injury, which was of difference in statistics (p < 0.05). NSCs transplantation can effectively alleviate the formation of glial scar, enhance the survival of hippocampal neurons and improve cognitive function defects in rats with TBI. The underlying mechanism may be related to their effects on inhibiting the release of Glu and maintaining the content of GABA, so as to down-regulate excitotoxicity of neurotransmitter and improve the micro-environment in injured sites.

Low-dose bisphenol A exposure impairs learning and memory ability with alterations of neuromorphology and neurotransmitters in rats

To investigate the developmental neurotoxicity of environmental bisphenol A (BPA) exposure for infants and children, postnatal rats were used as the animal model and were divided into four groups. Then, they were treated with different concentrations of BPA (i.e., 0, 0.5, 50, or 5000 μg/kg·bw/day of BPA as the control, low-, medium- and high-exposed group) from postnatal days 7 to 21. Y-maze tests, Golgi-Cox assays and liquid chromatography-tandem mass spectrometry (LC/MS/MS) were performed to test the changes of learning and memory ability, hippocampal neuromorphology and neurotransmitter levels, respectively. The results showed that the BPA-exposed rats, especially the low- and high-exposed rats, needed more trials and longer times to qualify for the learned criterion than the control rats. Additionally, rats after low- or high-exposure to BPA exhibited decreased DG dendritic complexity and reduced CA1 and DG dendritic spine densities in the hippocampus. Low-dosage BPA treatment could significantly alter the neurotransmitter contents in the hippocampus. In male rats, the levels of glutamic acid (Glu) and acetylcholine increased, while the 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) levels decreased, which lead to an unbalanced Glu/GABA ratio. However, in female rats, only 5-HT levels decreased. In conclusion, postnatal exposure to BPA could sex- and dose-dependently disrupt dendritic development and neurotransmitter homeostasis in the rat hippocampus. The impaired spatial learning and memory ability of rats induced by low-dose BPA is associated with both disrupted dendritic development and neurotransmitter homeostasis in the hippocampus.