Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

Change of Extracellular Glutamate Level in Striatum during Deep Brain Stimulation of the Entopeduncular Nucleus in Rats

OBJECTIVE: Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson’s disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum.METHODS: Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed.RESULTS: Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category.CONCLUSION: Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.

Decreased Serum Glutamate Levels in Male Adults with Internet Gaming Disorder: A Pilot Study

OBJECTIVE: Alteration in glutamatergic neurotransmission and dopaminergic dysfunction has been implicated in both the initiation and expression of addiction related behaviors. This pilot study was aimed to investigate the serum levels of glutamate and dopamine in adults with internet gaming disorder (IGD). METHODS: We measured serum levels of glutamate and dopamine in male participants with IGD (n=26) and age-matched healthy controls (n=25). Clinical interviews were performed to identify IGD and to rule out psychiatric comorbidities. Serum levels of glutamate and dopamine were examined by enzyme immunoassays using ELISA Kits. RESULTS: Serum levels of glutamate were lower among IGD than control (IGD: 24.184±12.303 μg/ml; control: 33.676±12.413μg/ml; t=2.742, p=0.008), while levels of dopamine did not differ between. Serum glutamate and dopamine levels did not correlate with gaming hours and exposure to game in the IGD group. But serum glutamate levels were positively correlated with the dopamine levels (r=0.360, p=0.013). CONCLUSION: Our results suggest that altered glutamatergic neurotransmission may contribute to the pathophysiology of IGD.

Trichotillomania: a good response to treatment with N-acetylcysteine

Abstract: Trichotillomania is considered a behavioral disorder and is characterized by the recurring habit of pulling one's hair, resulting in secondary alopecia. It affects 1% of the adult population, and 2 to 4.4% of psychiatric patients meet the diagnostic criteria. It can occur at any age and is more prevalent in adolescents and females. Its occurrence in childhood is not uncommon and tends to have a more favorable clinical course. The scalp, eyebrows and eyelashes are the most commonly affected sites. Glutamate modulating agents, such as N-acetylcysteine, have been shown to be a promising treatment. N-acetylcysteine acts by reducing oxidative stress and normalizing glutaminergic transmission. In this paper, we report a case of trichotillomania with an excellent response to N-acetylcysteine.

Effect of theanine pretreatment on DNA repair function in neurons during brain ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effect of theanine pretreatment on DNA repair function in neurons during brain ischemia-reperfusion (I/R) injury in rats.Methods One hundred and eight male Sprague-Dawley rats,weighing 290-310 g,aged 15 weeks,were randomly divided into 3 groups (n =36 each) using a random number table:sham operation group (S group),I/R group and theanine pretreatment group (T group).Global cerebral I/R was produced by 4-vessel occlusion method.Bilateral vertebral arteries were electrically cauterized,and bilateral common carotid arteries were clamped for 6 min.Theanine 1 g/kg was injected intravenously at 4 h before clamping bilateral common carotid arteries in T group,and the equal volume of normal saline was given in the other two groups.At 2,6,12,24,48 and 72 h of reperfusion,6 rats were selected in each group and sacrificed,the brains were removed,and the hippocampus was isolated for determination of the number of viable neurons in the hippocampal CA1 region (with a light microscope),apoptosis in neurons in the hippocampal CA1 region (by TUNEL),and expression of DNA repair protein X-ray repair cross-complementing group 1 (XRCC1) and Ku70 (by immunohistochemistry).The apoptotic index was calculated.Results Compared with S group,the number of viable neurons was significantly decreased,and the apoptotic index was significantly increased at 6,12,24,48 and 72 h of reperfusion,and the expression of XRCC1 and Ku70 was significantly down-regulated at 2,6,12,24,48 and 72 h of reperfusion in I/R group (P＜0.01).Compared with I/R group,the number of viable neurons was significantly increased at 12,24,48 and 72 h of reperfusion,the apoptotic index was significantly decreased at 6,12,24,48 and 72 h of reperfusion,and the expression of XRCC1 and Ku70 was significantly up-regulated at 2,6,12,24,48 and 72 h of reperfusion in T group (P ＜ 0.01).Conclusion The mechanism by which theanine pretreatment attenuates brain I/R injury is related to enhancement of DNA repair function and reduction of neuronal apoptosis in rats.

A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons / 대한해부학회지

We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury.

Regulation of glutamate level in rat brain through activation of glutamate dehydrogenase by Corydalis ternata

When treated with protopine and alkalized extracts of the tuber of Corydalis ternata for one year, significant decrease in glutamate level and increase in glutamate dehydrogenase (GDH) activity was observed in rat brains. The expression of GDH between the two groups remained unchanged as determined by Western and Northern blot analysis, suggesting a post-translational regulation of GDH activity in alkalized extracts treated rat brains. The stimulatory effects of alkalized extracts and protopine on the GDH activity was further examined in vitro with two types of human GDH isozymes, hGDH1 (house-keeping GDH) and hGDH2 (nerve-specific GDH). Alkalized extracts and protopine activated the human GDH isozymes up to 4.8-fold. hGDH2 (nervespecific GDH) was more sensitively affected by 1 mM ADP than hGDH1 (house-keeping GDH) on the activation by alkalized extracts. Studies with cassette mutagenesis at ADP-binding site showed that hGDH2 was more sensitively regulated by ADP than hGDH1 on the activation by Corydalis ternata. Our results suggest that prolonged exposure to Corydalis ternata may be one of the ways to regulate glutamate concentration in brain through the activation of GDH.

Glutamate transport across blood brain barrier after transient global ischemia/reperfusion in rats / 中国病理生理杂志

AIM: to study the change of glutamate(Glu) transport across blood brain barrier(BBB) in rat following forebrain ischemia/reperfusion. METHODS: BBB unidirectional transfer constant(K i) for [3H]-Glu in rat hippocampus, cerebral cortex and striatum were determined after rats were subjected to cerebral ischemia 10 min (two-carotid occlusion plus hypovolemic hypotension) followed by 0.17, 2, 6 and 24 h of reperfusion. The recovery of [3H]-Glu in cerebrum was also determined after intracerebral injection of [3H]-Glu in another experiment. RESULTS: Compared with control rat brain, K i for [3H]-Glu significantly(P

Effect of altitude hypoxia on glutamate, aspartate and NOS in the rat hypothalamus / 中国病理生理杂志

AIM: To observe the effect of altitude hypoxia on glutamate, aspartate and nitric oxide synthase (NOS) in the rat hypothalamus. METHODS: Using altitude hypoxia model, amino acid analysis system and the NADPH-d histochemistry, we determined the content of glutamate, aspartate and the number of NADPH-d neurons in the rat hypothalamus. RESULTS: After altitude hypoxia, the contents of glutamate, aspartate in the hypothalamus of rats were increased significantly, densely and deeply stained NADPH-d neurons were seen in hypothalamic paraventricular nucleus (PVN)and supraoptic nucleus(SON). If rat were pretreated with the NMDA receptor blockers Ketamine (ip,40 mg/Kg)or AP-V(i.c.v, 10 ?g) , the number of NADPH-d neurons in the rat hypothalamic PVN and SON was markedly less than that in corresponding altitude hypoxia group. CONCLUSION: NMDA receptor may take part in the expression of hypothalamic NOS induced by altitude hypoxia.

Glutamate transport across blood brain barrier after transient global ischemia/reperfusion in rats / 中国病理生理杂志

AIM: To study the change of glutamate (Glu) transport across blood brain barrier ( BBB ) in rat following forebrain ischemia/reperfusion. METHODS: BBB unidirectional transfer constant ( Ki ) for [3H] - Glu in rat hippocampus, cerebral cortex and striatum were determined after rats were subjected to cerebral ischemia 10 min ( two - carotid occlusion plus hypovolemic hypotension) followed by 0.17, 2, 6 and 24 h of reperfusion. The recovery of [3H] - Glu in cerebrum was also determined after intracerebral injection of [3H] - Glu in another experiment. RESULTS: Compared with control rat brain, Ki for [3H] -Glu significantly( P < 0.05) decreased at 10 ain cerebral ischemia followed by 0.17, 2 and 6 h of reperfusion. At 5 min after intracerebrally injecting [3H] - Glu , recovery of [3H] - Glu in control rat brain was 23.83%. The result indicted that there is a Glu efflux mechanism on BBB. This efflux was not significantly inhibited by pretreatment of 200 mg/L probenecid. After 10 ain cerebral ischemia followed by 2 h of reperfusion, the recovery( 13.13 % ) was significantly lower than contro( P < 0.05), its recovery was only 55 % of the control. The result indicated that cerebral ischemia/reperfusion may enhanced the effiux of [3H] -Glu from brain. CONCLUSION: Cerebral ischemia/reperfusion significantly reduced Glu BBB transport from plasma to brain and enhanced effiux of Glu from brain.

Effect of Xinmailing Solution on neuronal cell injury induced by glutamate / 中国病理生理杂志

AIM: To detect the effects of Xinmailing Solution and MK-801 on injury of neuronal cell induced by glutamate. METHODS: Cultured neuronal cell injuried by glutamate was prepared and the content of malondialdehyde and nitrite in cell supernatant was measured. Morphology changes were also observed with discrepancy microscope at the same time. RESULTS: Xinmailing Solution and MK-801 attenuated cell injury induced by glutamate,and inhibited increase in malondialdehyde and nitrite in cell supernatant. CONCLUSION: Xinmailing Solution had a protective effect on neuronal cell at cell level.

O transtorno glutamatérgico na esquizofrenia / Glutamatergic disorder in schizophrenia

A excitoxicidade relacionada ao neurotransmissor aminoácido glu- ta mato e ao seu receptor NMDA (n-metil-d-aspartato) consiste em um mecanismo de elevado potencial para explicar a fisiopatologia da esquizofrenia. Os neurolépticos atípicos clozapina e olanzapia têm potencial para proteger contra a neurotoxicidade gerada pelos antagonistas de NMDA.

Excitotocicity due to glutamate and its NMDA (N-methyl-D- aspartate) receptor are a possible mechanism for the physiopatholoy of schizophrenia. The atipical neuroleptic drugs clozapine and olanzapina present the potencial to protect against neu- rorocity caused by NMDA antagonists.

Activation of group I metabotropic glutamate receptors in rat striatum induces contralateral rotation / 中国病理生理杂志

AIM: To study the subtype of metabotropic glutamate receptors (mGluRs) which induce contralateral rotations of rats after mGluRs activation. METHODS: Turning movement was measured at 6 h after agonist or antagonist of mGluRs was microinjected into rat striatum. RESULTS: tACPD, an agonist of mGluRs, at 500 nmol and 1 000 nmol induced contralateral rotations of rats. L-AP 3, MCPG and dantrolene attenuated the turning effect of tACPD. DHPG, a selective agonist of group I mGluRs, mimicked the effect of tACPD. The effect of DHPG was blocked by MCPG, LY367385 (antagonist of mGluR 1) and MPEP (antagonist of mGluR 5), and abolished by pretreatment with reserpine (5 mg/kg). CONCLUSION: These results indicated the activation of group I mGluRs in rat striatum induced turning effect, which may be associated with the mobilization of intracellular Ca 2+ stores and dependant on the existence of dopamine.

Effects of glucose and Mg~(2+) in the neurons damaged by glutamate / 中国病理生理杂志

AIM and METHODS: To observe the effects of glucose-free and Mg 2+ -free in the extracellular fluid on the changes of [Ca 2+ ] i in the cerebro-cortical neurons damaged by 1 mmol/L glutamate using laser confocal scanning microscope. RESULTS: Both frequency and amplitude of neuronal calcium oscillation induced by glutamate were lowered in glucose-free and Mg 2+ -free buffers. The basic [Ca 2+ ] i concentration was lowered in the former case , but it was elevated in the latter case. CONCLUSION: Mg 2+ -free aggravates [Ca 2+ ] i overload induced by 1 mmol/L glutamate ,under certain conditions the glucose-free might resist damage role of glutamate and Mg 2+ -free.