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Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.
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Animals , Mice , Cognition , Cognition Disorders , Depression , Glutamic Acid , Herbal Medicine , Learning , Lignans , Memory , Mood Disorders , Physical Exertion , SchisandraABSTRACT
Objective To study the effects of ceftriaxone sodium(Cef) on the seizures and the expression of glutamate transporter (GLT-1) in kainic acid (KA) epilepsy model.Methods Firstly, a chronic spontaneous seizure mouse model was established by unilateral hippocampal injection of KA and monitored by vEEG technique to record seizures.The experimental group received intraperitoneal injection of Cef 200 mg/(kg·d) and the control group received normal saline.Seizure frequency, interictal spike waves and histological phenotypes were recorded to evaluate the function of Cef.Then we use the Western blot to detect the effect of expression for GLT-1.Results Unilateral hippocampal injection of KA 200 ng successfully established the mesial temporal lobe epilepsy model.Cef can reduce the seizures from 2.145 times/day to 1.597 times/day, decreased by 31.2% with a statistical significance(P<0.05).Cef treatment did not significantly enhance the expression of GLT-1.Conclusions Intraperitoneal injection of Cef partially inhibites the seizures of KA model, but the expression of GLT-1 in hippocampus is not enhanced.It is suggested that ceftriaxone may inhibit seizures through other mechanisms.
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Aim To investigate the effect of p38 MAPK AS-ODNs on the expression of GLT-1 during the induction of brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP).Methods Eighty healthy male Wistar rats with permanent occlusion of the bilateral vertebral arteries were randomly divided into 6 groups: ①Sham group (n=10);②CIP group (n=10);③ischemic insult (Ⅱ) group (n=10);④CIP+Ⅱ group (n=10);⑤p38 MAPK AS-ODNs+CIP+Ⅱ group (n=30);⑥p38 MAPK S-ODNs+CIP+Ⅱ group (n=10).Group ⑤ was divided into 5 nmol, 10 nmol and 15 nmol subgroups according to the dose of p38 MAPK AS-ODNs (n=10).The dose of p38 MAPK S-ODNs was 15 nmol.All the rats were sacrificed 6 h and 2 d after the sham operation or the last time of global brain ischemia reperfusion.Western blot and immunohistochemistry analysis were used for detecting the expression of p-p38 MAPK and GLT-1 protein.Results CIP moderately up-regulated the expression of p-p38 MAPK and significantly up-regulated the expression of GLT-1 protein, inhibited the excessively up-regulation of p-p38 MAPK and the down-regulation of GLT-1 induced by ischemic insult.p38 MAPK AS-ODNs significantly inhibited the up-regulation of p-p38 MAPK and GLT-1 protein in a dose-dependent manner during the induction of brain ischemic tolerance by CIP.Conclusion p38 MAPK AS-ODNs inhibit the up-regulation of GLT-1 during the induction of brain ischemic tolerance induced by CIP.
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Objective: To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord. Methods: Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining. Results: GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05). Conclusions: After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited.
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Objective:To sduty the effect of β-lactam antibiotics efiriaxone on the levels of glutamate and glutamate transporter subtype-1 in hippocampus following traumatic brain injury in rats.Methods: All rats were divided randomly into three groups:sham group;TBI group and CTX group.The rat model of TBI were made by modified Feeney method ,and treated with ceftriaxone immediately after injury ( 200 mg/kg ).Wet-dry weight method was used to evaluate brain edema.The content of glutamate in hippocampus was measured with the high performance liquid chromatography.The expression of GLT-1 in hippocampus areas was tested by immunohisto-chemical and Western blot methods.Results:Compared with TBI group ,TBI-induced cerebral edema was significantly attenuated ( P<0.05 ) , the content of glutamate in hippocampus was were significantly decreased ( P<0.05 ) , the level of GLT-1 were significantly increased in CTX group ( P<0.05 ).Conclusion: β-lactam antibiotics ceftriaxone can block the excitatory neurotoxicity , reduce the extent of brain edema.
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OBJECTIVE@#To observe the effect of subarachnoid nerve block anesthesia on glutamate transporter glutamate-aspartate transporter (GLAST) and GLT-1 expressions in rabbits, and to investigate the effect of peripheral nerve anesthesia on the morphology and function of the spinal cord.@*METHODS@#Twenty healthy New Zealand white rabbits were randomly divided into two groups: the experimental group and control group; with 10 rabbits in each group. For spinal nerve anesthesia, 5 g/L of bupivacaine was used in the experimental group, and sterile saline was used in the control group. After 30 min of cardiac perfusion, GLAST and GLT-1 protein expression in spinal neurons were detected by immunohistochemistry and immunofluorescence staining.@*RESULTS@#GLAST and GLT-1 protein-positive cells increased in neurons in the experimental group, compared with the control group (P < 0.05).@*CONCLUSIONS@#After subarachnoid nerve block anesthesia, rabbit glutamate transporter GLAST and GLT-1 expression is increased; and spinal cord nerve cell function is inhibited.
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In the present study, we examined the distribution and amount of two important glutamate transporters, GLT-1 and GLAST in the cerebellum of young and aged rats. Sprague-Dawley rats were used at the age of three months for young control (n=3) and 24 months for aged group (n=4). After transcardial perfusion with 4% paraformaldehyde, brain sections were immunostained for GLT-1, and GLAST. We found that GLT-1- and GLAST-immunoreactive materials were diffusely distributed throughout the gray matter of the cerebellum. Pre-embedding immunoelectron microscopic study demonstrated that the two glutamate transporters in the cerebellum were restricted to glial cells with astrocytic features. The intensity of GLT-1-immunostaining in the cerebellum appeared to be higher in aged rats than in young rats whereas GLAST-immunostaining decreased with aging. Western blot results were also consistent with the immunohistochemical observations. Conclusively, GLT-1 and GLAST expression in the rat cerebellum was changed with aging, i.e, increase of GLT-1 and decrease of GLAST expression with aging, which suggests that the two glutamate transporters might be regulated by different underlying mechanisms with aging.
Subject(s)
Aged , Animals , Humans , Rats , Aging , Blotting, Western , Brain , Cerebellum , Formaldehyde , Glutamic Acid , Neuroglia , Perfusion , Polymers , Rats, Sprague-DawleyABSTRACT
The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.
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Objective To study the toxic effects of Rotenone on glutamate transporter and glutamine synthetase in rat brain.Methods The glutamate levels in the striatum of SD rats were detected by high performance liquid chromatography(HPLC),the expression of glutamate tansporter mRNA and proteins were detected by RT-PCR and Western blotting and the activity of glutamine synthetase was determined by using GS detect kit.Results Rotenone was shown to increase the release of glutamate in rat striatum,the expression of glutamate/aspartate transporter(GLAST)mRNA and protein decreased significantly in 0.6 mg/kg and 1.2 mg/kg Rotenone intoxicated groups,but the expression of GLT-1 and the activity of GS enhanced obviously.Conclusion Down-regulation of GLAST may be responsible for increased Glu level in rat brain induced by Rotenone,but the increased expression of GLT-1 and GS activity may represent a protective mechanism of the brain cells by limiting the neurotoxicity of Glu.