Characterization of group Ⅰ metabotropic glutamate receptors in rat superior cervical ganglion and their changes following chronic intermittent hypoxia / 解剖学报

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Autoimmune cerebellar ataxia with positive anti-Homer3 antibody: a case report and literature review / 中华神经科杂志

Autoimmune cerebellar ataxia (ACA) is a cerebellar syndrome mediated by autoimmune mechanisms, and ACA with positive anti-Homer3 antibody is very rare. This article reports a 55-year-old male patient admitted to Qilu Hospital, Shandong University, due to dizziness and walking instability for 22 days. The serum and cerebrospinal fluid showed positive results for anti-Homer3 antibody, and the symptoms improved after intravenous immunoglobulin combined with hormone therapy. Based on the review of the case data and relevant literature reports, the pathogenesis, clinical manifestations, auxiliary examination, treatment and prognosis of ACA with positive anti-Homer3 antibody are analyzed, so as to deepen the understanding of clinicians and improve the diagnosis and treatment level.

Neurobiological mechanisms in the regulation of conditioned fear memory by the retrieval-extinction paradigm / 中华行为医学与脑科学杂志

Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

The Interaction Between CAL and mGluR1 Alleviates Cytotoxicity Induced by mGluR1 Overactivation / 中国生物化学与分子生物学报

Glutamate excitotoxicity mediated by metabotropic glutamate receptor 1 (mGluR1) overexpression or overactivation plays an important role in the development of Parkinson's disease (PD). Although clinical trials support the therapeutic potential of certain mGluR negative allosteric modulators (NAMs), there are still some limitations of precise modulation of mGluR using NAMs. Thus, the identification of small molecules or endogenous genes that facilitate mGluR1 modulation might be potentially beneficial for PD treatment. We determined the role of interacting partner cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in overactivated mGluR1-mediated cell apoptosis and signaling pathway in vitro and in vivo. HEK293 cells were used as an experimental tool to directly examine the interaction between CAL and mGluR1. We found that agonist of mGluR1 significantly enhanced the interaction between CAL and mGluR1 (P< 0. 05). Furthermore, CAL suppressed overactivated mGluR1-induced cell apoptosis and the activation of mGluR1 downstream signaling pathways. CAL overexpression relieved rotenone-induced neuron death (P< 0. 001) by inhibiting the activation of mGluR1-mediated signaling pathways in rotenone-induced rat model of PD. This study may reveal a new mechanism of mGluR1 activity regulation, and hopefully provide a novel molecular mechanism for the nervous system related diseases.

Research progress on excitotoxicity of glutamate and its modulators / 中国药理学通报

Excitotoxicity mainly refers to the toxic effect of the excitatory neurotransmitter glutamate.Long-term activation of glutamate receptors will cause a series of neurotoxicity, eventually leading to the loss of neuronal function and cell death.Triggering excitotoxicity may involve changes in glutamate and calcium metabolism, dysfunction of glutamate transporter, N-methyl-D-aspartate receptor(NMDAR)and mitochondria, and production of ROS.Therefore, we here review the occurrence of these mechanisms and introduce the pathological mechanism of glutamate excitotoxicity in Alzheimer's disease(AD), Parkinson's disease(PD), depression and epilepsy.Finally, this review briefly describes the regulatory effects of broad-spectrum glutamic satellite modulators, marine compounds and Chinese herbal medicines on the glutamatergic system.

Research progress of metabotropic glutamate receptor 5 in related central nervous system diseases / 中国药科大学学报

@#As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.

Research progress on the effect of transcranial magnetic stimulation on learning, memory and plasticity of brain synaptic / 生物医学工程学杂志

Transcranial magnetic stimulation (TMS) as a noninvasive neuromodulation technique can improve the impairment of learning and memory caused by diseases, and the regulation of learning and memory depends on synaptic plasticity. TMS can affect plasticity of brain synaptic. This paper reviews the effects of TMS on synaptic plasticity from two aspects of structural and functional plasticity, and further reveals the mechanism of TMS from synaptic vesicles, neurotransmitters, synaptic associated proteins, brain derived neurotrophic factor and related pathways. Finally, it is found that TMS could affect neuronal morphology, glutamate receptor and neurotransmitter, and regulate the expression of synaptic associated proteins through the expression of brain derived neurotrophic factor, thus affecting the learning and memory function. This paper reviews the effects of TMS on learning, memory and plasticity of brain synaptic, which provides a reference for the study of the mechanism of TMS.

Critical role of metabotropic glutamate receptor 4 in bone marrow-derived dendritic cells in the Th17 cell differentiation and the melanogenesis of B16 cells

Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4+ T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4+ T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.

Regulatory effect of metabolic glutamate receptor 1 on maltolate aluminum-induced synaptic plasticity in rats / 中国职业医学

OBJECTIVE: To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1). METHODS: Specific pathogen free healthy adult male SD rats were randomly divided into control group, aluminum group, aluminum agonist group and aluminum antagonist group, 8 rats in each group. The rats in the control group received no treatment; the rats in aluminum group were injected with 5 μL 10 mmol/L maltolate aluminum solution into the lateral ventricle; the rats in aluminum agonists and aluminum antagonist group were injected with 3 μL 10 mmol/L maltolate aluminum solution plus 2 μL 0.1 μmol/L mGluR1 agonist or 2 μL 0.2 μmol/L mGluR1 antagonists into the lateral ventricle, respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days. After maltolate aluminum exposure, the amplitudes of long-term potentiation(LTP) in hippocampal CA1 region of rats were measured, and the relative expression levels of mRNA and protein of mGluR1, N-methyl-D-aspartate receptor(NMDAR1) and protein kinase C(PKC) in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting. RESULTS: The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05). Compared with the control group, the relative expression of mGluR1 mRNA and protein in the aluminum group increased, the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05). Compared with the aluminum group, the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased, while the NMDAR1 mRNA decreased(P<0.05); the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased, while the NMDAR1 mRNA and protein increased(P<0.05). Compared with the aluminum agonist group, the relative expression of mGluR1 mRNA and protein decreased, while the NMDAR1 mRNA and protein increased in the aluminum antagonist group(P<0.05). The relative expression level of PKC mRNA and protein in aluminum agonist group and aluminum antagonist group was not statistically significant(P>0.05), and there was no statistical significance in these two groups compared with control group and aluminum group(P>0.05). CONCLUSION: Maltolate aluminum exposure can inhibit synaptic plasticity by inhibiting LTP in hippocampus of rats, and the mechanism may be related to the regulation of NMDAR1 expression by mGluR1.

Research progress in metabotropic glutamate receptor 5 and related nervous system diseases / 中国药理学与毒理学杂志

The metabotropic glutamate receptor 5 (mGluR5), one of the most important mGluRs, exerts a biological effect through the second messenger. mGluR5 is mainly distributed in the cerebral cortex, hippocampus, and striatum in the form of dimers. It participates in neuronal excitability network regulation, neurogenesis, and synaptic plasticity associated with learning and memory by activating signaling pathways such as protein kinase C-inositol 1, 4, 5-triphosphate-diacylglycerol-Ca2+ and phosphatidylinositol 3-kinase-mammalian target of Rapamycin. Recently, mGluR5 has been confirmed to play an important role in diseases of the nervous system. Studies have shown that over-activation or inhibition of mGluR5 is closely related to the pathological processes of a variety of neurological diseases. A variety of drugs that selectively activate or inhibit mGluR5 activity have been used in the treatment of neurological diseases.

Role of group mGluR in low dose ketamine protecting learning and memory function after electroconvulsive shock in depression rats / 上海交通大学学报（医学版）

Objective • To investigate the role of group I metabotropic glutamate receptor (mGluR) in the regulation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic plasticity in low dose ketamine protecting learning and memory function after modified electroconvulsive shock (MECS). Methods • The 2-3-month-old Sprague Dawley (SD) rats were used to establish depression models with chronic unpredictable mild stress. Ten healthy rats were used as the control group (group C), and another 30 depressed rats were randomly divided into group D, group M, and group KM. Group C was not treated, group D was treated with pseudo-MECS after intraperitoneal injection of normal saline, group M was given intraperitoneal injection of propofol, and group KM was given intraperitoneal injection of propofol combined with low-dose ketamine (10 mg/kg). Both group M and group KM underwent MECS. The sucrose preference test was used to evaluate the depression status. The Morris water maze was used to detect the spatial learning and memory function. The expression of NMDAR1, mGluR1 and mGluR5 proteins in the hippocampus was detected by Western blotting. Another 36 depressed rats were randomly divided into 6 groups: group DE, group m1E, group m5E, group DE', group m1E', and group m5E'. Group DE and group DE' were perfused with artificial cerebrospinal fluid alone. Group m1E and group m1E' were perfused with artificial cerebrospinal fluid containing mGluR1 blocker. Group m5E and group m5E' were perfused with artificial cerebrospinal fluid containing mGluR5 blocker. Long-term potentiations (LTP) were detected in group DE, group m1E, and group m5E. NMDAR-mediated field potentials (fEPSPNMDAR) were detected in group DE', group m1E', and group m5E'. Results • After treatment, the sucrose preference percentages of group M and group KM increased compared with group D (P<0.05), the escape latencies (EL) of group M and group KM were prolonged (P<0.05), and the space exploration times (SET) were shortened (P<0.05). Compared with group M, the EL of group KM was shortened (P<0.05), and the SET was prolonged (P<0.05). Compared with group D, the expression levels of NMDAR1, mGluR1 and mGluR5 in group M and group KM decreased (P<0.05). Compared with group M, the expression levels of NMDAR1, mGluR1 and mGluR5 in group KM increased (P<0.05). Compared with group DE, the LTP decreased in group m1E and group m5E (P<0.05). Compared with group DE', the fEPSPNMDAR of group m1E' and group m5E' decreased (P<0.05). Conclusion • Ketamine up-regulates NMDAR1 and group mGluR expression to enhance the activation of NMDAR in the hippocampus which may be responsible for the protective effects on spatial learning and memory function in depression rats undergoing MECS.

The mTORC1 signaling network underlying the pathogenesis and treatment of depression:new insights into rapid-acting antidepressant therapies / 中国药理学与毒理学杂志

Depression is a devastating mental disorder and major depressive disorder (MDD) that afflicts 16％ of the global population at some point in their lives. Currently available classical antide-pressants (SSRIs, SNRIs, TCAs and MOIs), require a minimum of 2–4 weeks of continuous treat-ment to elicit therapeutic relief in depressed patients and are associated with high rates of non-respon-siveness, and limited duration of efficacy. Therefore, faster-acting antidepressant therapies are need-ed,particularly for patients at risk for suicide for current therapies for depression.Although the molecu-lar mechanisms underlying the pathogenesis of depression are still largely unclear, previous studies have suggested that modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling may have beneficial neuroprotective and antidepressant effects. Here, we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling network. We also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy (e.g. ketamine, scopolamine, GLYX-13, (2R,6R)-HNK, Ro-256891 etc.) and discuss future research directions. Studies on prospec-tive next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs) agonists or activators)that activate the mTORC1 signaling pathway free of ketamine's adverse effects.

Protective effect of metabotropic glutamate receptor 1 negative allosteric modulator JNJ16259685 on neuron after subarachnoid hemorrhage in rats / 中国脑血管病杂志

Objective To investigate the protective effect and its mechanism of metabotropic glutamate receptor 1 ( mGluR1) negative allosteric modulator JNJ16259685 on neuron after subarachnoid hemorrhage (SAH) in rats. Methods Ninety SPF-grade SD male rats were selected. They were randomly divided into 3 groups:sham operation group (n=18),SAH+placebo group (n=36),and SAH+JNJ16259685(JNJ) group (n=36). A SAH model was induced by intravascular puncture. SAH +placebo group received intraperitoneal injection of aseptic water containing 5% dimethyl sulfoxide (DMSO) at 2,24 and 48 h after operation. The SAH+JNJ group was intraperitoneally injected with 1 mg/kg JNJ16259685 ( dissolved in sterile water in 5% DMSO). Garcia scoring criteria were used to assess neurological deficits at 72 h after SAH. Dry and wet weight method was used to detect brain edema. Evans Blue method was used to assess blood-brain barrier permeability. A calcium assay kit was used to detect the mitochondrial calcium ion concentration. Immunofluorescence staining was used to observe neuronal apoptosis. GraphPad 7. 0 software was used to conduct one-way analysis of variance in all indicators among the 3 groups. Results Compared with the sham operation group,the Garcia score (11. 0 ± 0. 4) decreased in the SAH+placebo group. The water content in left and right hemispheres was 80. 5 ± 0. 1% and 80. 3 ± 0. 2% respectively,the Evans blue dye extravasation (2. 8 ± 0. 2),basal cortical mitochondrial calcium ion concentration (2. 5 ± 0. 3),and neuronal apoptosis in basal cortex and hippocampus CA1 region (the number of active caspase-3/NeuN positive cells was 300 ±30/mm2and 20 ± 2/mm respectively) increased (all P<0. 05);and the Garcia score (13. 0 ± 0. 5) was significantly higher in the SAH+JNJ group than in the SAH+placebo group. Water content in left and right hemispheres was 79. 8 ± 0. 2% and 79. 3 ± 0. 1% respectively,Evans blue dye extravasation (1. 8 ±0. 2),basal cortex mitochondrial calcium ion concentration (1. 7 ± 0. 1),basal cortex and the number of neuronal apoptosis in hippocampal CA1 region (the number of active caspase-3/NeuN positive cells were 180 ± 10/mm2,12 ±2/mm) reduced compared with the SAH+placebo group (all P<0. 05). Conclusion After SAH,JNJ16259685 relieves cerebral edema and reduces blood-brain barrier permeability,inhibits the increase of cortical mitochondrial calcium ion concentration,and reduces neuronal apoptosis,thereby exerting neuroprotective effects.

Effect of Serum on Cultured Astrocytes Morphology and Expression of Aquaporin-4 in Rats / 中国康复理论与实践

Objective To explore the effect of blood-brain barrier disruption on expression of AQP-4,through comparing the cell morphology and the expression of aquaporin-4(AQP-4)of cultured astrocytes in medium with and without fetal bovine serum(FBS). Methods Cerebral cortical astrocytes from female Wistar rats were cultured in serum free medium,DMEM supplement-ed with 10% FBS,and serum free medium supplemented with 10% FBS.Phase contrast microscope was used to detect the cell morphology and cell size. Immunofluorescence staining and reverse real-time quantitative poly-merase chain reaction(RT-qPCR)were used to examine the expression of glial fibrillary acidic protein(GFAP), AQP-4 and metabotropic glutamate receptor 5(mGluR5). Results Astrocytes in serum free medium showed extensive process bearing morphology,small body and nucleus,and high refractivity.In contrast,in two kinds of 10% FBS-containing medium,astrocytes were flat with large body and nucleus,weak refractivity,as well as short process.Analysis of immunofluorescence staining and RT-qPCR revealed a down-regulation of GFAP and AQP-4 protein and mRNA expression in two kinds of 10% FBS-con-taining medium, compared with that in serum free medium (P<0.001), however, there was no difference in mGluR5 protein and mRNA expression(P>0.05). Conclusion FBS changed astrocyte morphology and down-regulated the expression of GFAP and AQP-4.

Effect of Catgut Implantation on Spatial Learning-memory Ability, Expression of Hippocampal Protein Kinase C Interacting Protein 1 and GluR 2 and Ca2+ Content in Rats with Chronic Ischemic Cognitive Impairment / 针刺研究

OBJECTIVE: To observe the effect of catgut embedment at "Baihui" (GV 20), "Dazhui" (GV 14), etc. on learning-memory ability, expression of hippocampal protein kinase C interacting protein 1 (PICK 1) and glutamate receptor 2 (GluR 2) proteins and level of calcium ions, so as to explore its mechanism underlying improvement of vascular cognitive impairment. METHODS: A total of 56 male SD rats were randomly divided into sham operation, model, catgut embedment and medication groups (n=14 in each). The chronic ischemic cognitive impairment model was established by permanent occlusion of bilate-ral common carotid arteries. The catgut embedment was applied to GV 20, GV 14, "Shenshu" (BL 23) and "Xuanzhong" (GB 39), once a week, for 4 weeks. Rats of the medication group received intraperitoneal injection of monosialate tetrahexose ganglioside sodium (GM-1, 0.33 mg/kg), once daily for 4 weeks. The rats' learning-memory ability was detected by Morris water maze tasks, pathological changes of hippocampal Nissl's bodies were tested by Nissl staining. The expression levels of PICK 1 and GluR 2 proteins in the hippocampus were detected by Western bolt (WB), and the concentration of calcium ions in the hippocampus tissue was measured by Bicinchoninic acid (BCA) assay. RESULTS: After modeling, the mean escape latencies of place navigation test were significantly increased while the crossing times of target platform quadrant of space probing test notably decreased in the model, catgut embedment and medication groups compared with their own individual pre-modeling (P0.05). CONCLUSION: Catgut implantation at GV 20 etc. can effectively improve the learning-memory ability in rats with chronic ischemic cognitive impairment, which may be related to its effects in down-regulating the expression of PICK 1 and calcium ion concentration and up-regulating the expression of AMPA receptor subunit GluR 2 protein in the hippocampus.

Relationship between metabotropic glutamate receptor 5 and N-methyl-D-aspartate receptor and their roles in diseases / 上海交通大学学报（医学版）

Metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor (NMDAR) belongs to metabotropic and ionotropic glutamate receptor family, respectively. In recent years, a lot of attention has been paid to these two types of glutamate receptors in the field of neuroscience and psychiatry. This article mainly summarized the research progress of the relationship between these two kinds of receptors and the influence of their relationship on different diseases.

Effects of Electroacupuncture on Expression of Glutamate Receptor Interacting Proteins 1 and 2 in Hippocampus of Rats with Alzheimer's Disease / 中国康复理论与实践

@#Objective To investigate the effect of electroacupuncture on the expression ofα-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptor associated protein glutamate receptor interacting protein (GRIP)1 and GRIP2 in hippocampal neurons of rats with Alzheimer's disease (AD) model induced by Aβ25-35. Methods 40 Male Sprague-Dawley rats were randomly divided into normal group, sham operation group, model group and electroacupuncture group with 10 rats in each group. The AD rat model was prepared by injecting Aβ25-35 in the hippocampus CA1 of rats, while the sham operation group was injected with equal amount of normal saline at the same loca-tion. On the second day after successful modeling, the electroacupuncture group received electroacupuncture at Baihui (DU20) and bilateral Shenshu (BL23) acupoints, once a day, 6 times a week for 2 weeks. The expression of GRIP1 and GRIP2 were detected with immunohisto-chemistry. Results There was no difference in the expression of GRIP2 and GRIP1 proteins in hippocampus between the normal group and sham operation group (t<1.7438, P>0.05), but was lower in the model group and the electroacupuncture group than in the sham operation group (t>9.5928, P<0.001), and was higher in the electroacupuncture group than in the model group (t>9.5326, P<0.05). Conclusion Elec-troacupuncture may increase the number of AMPA receptors on the postsynaptic membrane by increasing GRIP1 and GRIP2.

Genetic analysis of Ohtahara syndrome and atypical benign partial epilepsy coexisting in a family / 中华实用儿科临床杂志

Objective To explore the genetic etiologies in 2 siblings with different epileptic encephalopathies (EEs) diagnosed as Ohtahara syndrome(OS) and atypical benign partial epilepsy(ABPE) from one family.Methods The 2 brothers were diagnosed at the Pediatric Neurological Clinic of Peking University First Hospital in September 2013,whose clinical data were collected.The coding region of the syntaxin-binding protein 1 gene (STXBP1) and glutamate receptor subunit gene (GRIN2A) were detected by using Sanger sequencing in the 2 siblings.For the elder brother,targeted next-generation sequencing was further performed to detect the genes associated with epilepsy.Results The younger brother manifested focal motor seizures and tonic spasms in cluster at the age of 1 month.Interictal electroencephalogram (EEG) showed suppression-burst pattern.He was diagnosed as OS.The elder brother had seizure onset at age of 6 years old.Focal motor seizure during sleep was his seizure type.His EEG showed interictal discharges in Rolandic area primarily.Electrical status epilepticus during sleep,epileptic negative myoclonus and intellectual disabilities occurred during the course.He was diagnosed as ABPE.Brain magnetic resonance imagines for both of them were normal.Screening of STXBP1 mutations for the younger brother found a de novo heterozygous mutation:c.1672C ＞ T (p.Q558X).Gene detection for the elder brother and the parents showed negative results.Conclusions Coexistence of distinct EEs was reported in 2 brother siblings:the younger brother had OS associated with a novel nonsense mutation in STXBP1,and the elder brother had ABPE without genetic evidence.This study indicated that different pathological mechanisms might exist underlying the two different EEs in a family.

Effects of subacute 1-bromopropane inhalation on the expression of SYP,GluR2 and NR2B in hippocampus of male rats / 中国职业医学

OBJECTIVE: To study the potential effects of subacute 1-bromopropane( 1-BP) inhalation on the expression of synapse specific biomarkers synaptophysin( SYP),glutamate receptor 2( GluR2) and N-methyl-D-aspartate receptor 2B( NR2B) in the hippocampus of male rats. METHODS: Forty-eight specific pathogen free adult male Wistar rats were randomly divided into control group,low-,medium-,and high-dose groups according to body weight. Each group consisted of 12 rats. By dynamic inhalation intoxication method,the control group was exposed to fresh air,the dose groups were given 1 250,2 500 and 5 000 mg / m3 of 1-BP respectively,6 hours per day,5 days per week for continuous 4 weeks. After the exposure,the rats were executed and the whole brains were separated into cerebrum( included hippocampus),brainstem and cerebellum. Real time quantitative polymerase chain reaction and Western blot were used for detection of SYP,GluR2 and NR2 B mRNA and protein expression in hippocampus. RESULTS: Slow response and muscle strength descended in hind limbs were found in high-dose group in the 3rd week. Body weights of rats in high-dose group were lower than those of control group from the 1st to the 4th week( P < 0. 01). Weights of whole brain,cerebrum and brainstem in high-dose group were lower than those of control group( P < 0. 05). Rats in high-does group were found neuron necrosis in hippocampus cornu ammonis 3 and dentate gyrus region. No significant difference was found in SYP,GluR2 and NR2 B mRNA relative expression in all groups( P > 0. 05). No significant difference was found in SYP protein relative expression in different groups( P > 0. 05). The GluR2 protein relative expression in high-dose group was lower than that of control group( P < 0. 05). The NR2 B protein relative expression was higher than that of control group( P < 0. 05). CONCLUSION: The GluR2 and NR2 B protein expression in hippocampus can be potential biomarkers for 1-BP central neurotoxicity,but its physiological meaning needs further elucidation.

Advances of trentment in epilepsy / 国际儿科学杂志

Epilepsy is one of the most chronic central nervous system diseases.Based on the studies in recent years,treatment of epilepsy has made great progresses.This review discusses several aspects,such as traditional antiepileptic drugs,new antiepileptic drugs,antagonists of glutamate receptor,gap junction blocker,and glycolysis inhibitor,to provide new ideas and methods for the treatment of epilepsy.