Epilepsy ; genetics ; metabolism ; Glutamic Acid ; metabolism ; Humans ; Ion Channels ; genetics ; Receptors, GABA-A ; genetics

Animals ; Epilepsy ; genetics ; metabolism ; Genes, MDR ; Hippocampus ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Triazines ; pharmacology

The GATOR1 complex is located at the upstream of the mTOR signal pathway and can regulate the function of mTORC1. Genetic variants of the GATOR1 complex are closely associated with epilepsy, developmental delay, cerebral cortical malformation and tumor. This article has reviewed the research progress in diseases associated with genetic variants of the GATOR1 complex, with the aim to provide a reference for the diagnosis and treatment of such patients.
Humans ; GTPase-Activating Proteins/metabolism* ; Signal Transduction/genetics* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Epilepsy/genetics* ; Neoplasms

Despite a few genes that do not encode ion channels have been identified as implicating some kinds of human idiopathic epilepsies(IE) in recent years, but genetic discoveries have shown the ion channels to play a central role in genetic pathomechanism of IE. The gene mutations of ion channels are a common cause of some rare monogenic IE which could be so-called as channelopathies, and able to be applied to account for the questioned epileptic syndrome to minority of families and sporadic cases. However, more frustrating has been from the genetic research on more common IE with complex inheritance due to the unknown mode of inheritance, the phenotypic heterogeneity and the uncertainty of genetic overlap among syndrome subtypes, which have limited gene mapping. Absence epilepsy is a kind of common IE subtype and shows a complex way to inherit. Evidences from heredity investigation indicate that eleven genes are correlated with absence epilepsy, of which four encode the neuronal calcium channel subunits. Therefore, calcium channel genes may be considered as important candidates for involving in absence epilepsy. To focus the genetics research on calcium channel genes of absence epilepsy may be opening an optimal gate to the pathogenetic study of more common IE with complex inheritance, and benefit to elucidate the molecular mechanisms of absence epilepsy finally, one of the more common IE subtypes with complex inheritance.
Calcium ; metabolism ; Calcium Channels ; genetics ; physiology ; Epilepsy, Absence ; genetics ; physiopathology ; Genetic Predisposition to Disease ; genetics ; Humans ; Models, Biological

Fragile X syndrome (FXS) is one of the most prevalent mental retardations. It is mainly caused by the loss of fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein and can regulate the translation of its binding RNA, thus regulate several signaling pathways. Many FXS patients show high susceptibility to epilepsy. Epilepsy is a chronic neurological disorder which is characterized by the recurrent appearance of spontaneous seizures due to neuronal hyperactivity in the brain. Both the abnormal activation of several signaling pathway and morphological abnormality that are caused by the loss of FMRP can lead to a high susceptibility to epilepsy. Combining with the research progresses on both FXS and epilepsy, we outlined the possible mechanisms of high susceptibility to epilepsy in FXS and tried to give a prospect on the future research on the mechanism of epilepsy that happened in other mental retardations.
Brain ; physiopathology ; Epilepsy ; etiology ; genetics ; pathology ; Fragile X Mental Retardation Protein ; genetics ; metabolism ; Fragile X Syndrome ; complications ; genetics ; Humans ; RNA-Binding Proteins ; metabolism

OBJECTIVETo investigate the distribution and frequency of UGTIA6 A541G genetic polymorphism in Han epileptic children from Henan and to evaluate the effect of UGTIA6 A541G genetic polymorphism on serum concentrations of valproic acid.

METHODSThe method of gas chromatography was used to assay serum concentrations of valproic acid. UGTIA6 A541G genetic polymorphism was screened by PCR-RFLP. Direct sequencing was used to confirm the expected sequences of each genotype.

RESULTSThe genotypic frequencies of UGTIA6 A541G were as follows: AA in 76 cases, AG in 65 cases and GG in 6 cases. The mean values of serum concentrations of valproic acid in patients with A541G AA, AG and GG were 3.91+/-1.57, 3.59+/-1.39 and 3.73+/-1.28 microg/mL, respectively (dose-adjusted trough concentration on a mg/kg basis). There were no significant differences in serum concentrations of valproic acid among the three groups.

CONCLUSIONSUGT1A6 A541G gene polymorphism does not influence serum concentrations of valproic acid in Han epileptic children. Individual differences in serum concentrations of valproic acid may be attributed to many factors.

Adolescent ; Anticonvulsants ; metabolism ; Child ; Child, Preschool ; China ; ethnology ; Epilepsy ; drug therapy ; genetics ; metabolism ; Glucuronosyltransferase ; genetics ; Humans ; Polymorphism, Genetic ; Valproic Acid ; metabolism

OBJECTIVE: To observe the expression of cyclin-dependent kinase 5 (Cdk5) and p35 in rat hippocampus during pentetrazole kindling process and their relation with mossy fiber sprouting (MFS), and to investigate the role of Cdk5/p35 in epileptogenesis. METHODS: Altogether 120 healthy male SD rats were randomly divided into a control group and a pentylenetetrazole (PTZ) treated group. The epileptic models were established by the injection of PTZ intraperitoneally while the control rats were injected with an equal dose of saline. At the 3rd day, 1st week, 2nd week, 4th week, and 6th week after daily injection, Timm staining was performed in area CA3 and dentate gyrus, and the mRNA and protein of Cdk5 and p35 were analyzed in the hilus and stratum granulosum of dentate gyrus and area CA1 and CA3 of hippocampus, by in situ hybridization and immunohistochemistry, respectively. RESULTS: The expression levels of Cdk5 and p35 mRNA were significantly higher in the PTZ treated subgroups of the 3rd day, 1st week, 2nd week, and 4th week than those in the controls. Thereafter, the expression decreased to the level of controls. The expression level of Cdk5 and p35 protein increased from the 3rd day to 2nd week, and then gradually decreased to the level of the controls. Timm scores for PTZ groups were 1 to approximately 4 before kindling and 4~5 after kindling in area CA3. CONCLUSION Change of Cdk5/p35 expression in the hippocampus may play a role in epileptogenesis by influencing the process of mossy fiber sprouting.
Animals ; Cyclin-Dependent Kinase 5 ; genetics ; metabolism ; Epilepsy ; chemically induced ; metabolism ; Kindling, Neurologic ; drug effects ; metabolism ; Male ; Mossy Fibers, Hippocampal ; metabolism ; Pentylenetetrazole ; toxicity ; Phosphotransferases ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Ataxia ; genetics ; physiopathology ; Calcium Channels ; genetics ; physiology ; Epilepsy ; genetics ; physiopathology ; Genetic Diseases, Inborn ; genetics ; physiopathology ; Humans ; Hypokalemic Periodic Paralysis ; genetics ; physiopathology ; Malignant Hyperthermia ; genetics ; physiopathology ; Migraine with Aura ; genetics ; physiopathology ; Myopathy, Central Core ; genetics ; physiopathology ; Ryanodine ; metabolism ; Spinocerebellar Ataxias ; genetics ; physiopathology

Animals ; Epilepsy ; genetics ; Gene Expression Regulation ; drug effects ; Glial Fibrillary Acidic Protein ; genetics ; metabolism ; Hippocampus ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; pharmacology

OBJECTIVES: Epilepsy is a syndrome of central nervous system dysfunction caused by many reasons, which is mainly characterized by abnormal discharge of neurons in the brain. Therefore, finding new targets for epilepsy therapy has always been the focus and hotspot in neurological research field. Studies have found that 2-deoxy-D-glucose (2-DG) exerts anti-epileptic effect by up-regulation of K_ATP channel subunit Kir6.1, Kir6.2 mRNA and protein. By using the database of TargetScan and miRBase to perform complementary pairing analysis on the sequences of miRNA and related target genes, it predicted that miR-194 might be the upstream signaling molecule of K_ATP channel. This study aims to explore the mechanism by which 2-DG exerts its anti-epileptic effect by regulating K_ATP channel subunits Kir6.1 and Kir6.2 via miR-194. METHODS: A magnesium-free epilepsy model was established and randomly divided into a control group, an epilepsy group (EP group), an EP+2-DG group, and miR-194 groups (including EP+miR-194 mimic, EP+miR-194 mimic+2-DG, EP+miR-194 mimic control, EP+miR-194 inhibitor, EP+miR-194 inhibitor+2-DG, and EP+miR-194 inhibitor control groups). The 2-DG was used to intervene miR-194 mimics, patch-clamp method was used to detect the spontaneous recurrent epileptiform discharges, real-time PCR was used to detect neuronal miR-194, Kir6.1, and Kir6.2 expressions, and the protein levels of Kir6.1 and Kir6.2were detected by Western blotting. RESULTS: Compared with the control group, there was no significant difference in the amplitude of spontaneous discharge potential in the EP group (P>0.05), but the frequency of spontaneous discharge was increased (P<0.05). Compared with the EP group, the frequency of spontaneous discharge was decreased (P<0.05). Compared with the EP+miR-194 mimic control group, the mRNA and protein expressions of Kir6.1 and Kir6.2 in the EP+miR-194 mimic group were down-regulated (all P<0.05). Compared with the EP+miR-194 inhibitor control group, the mRNA and protein expressions of Kir6.1 and Kir6.2 in the EP+miR-194 inhibitor group were up-regulated (all P<0.05). After pretreatment with miR-194 mimics, the mRNA and protein expression levels of K_ATP channel subunits Kir6.1 and Kir6.2 were decreased (all P<0.05). Compared with the EP+2-DG group, the mRNA and protein expression levels of Kir6.1 and Kir6.2 in the EP+miR-194 mimic+2-DG group were down-regulated (all P<0.05) and the mRNA and protein expression levels of Kir6.1 and Kir6.2 in the EP+miR-194 inhibitor+2-DG group were up-regulated (all P<0.05). CONCLUSIONS The 2-DG might play an anti-epilepsy effect by up-regulating K_ATP channel subunits Kir6.1 and Kir6.2via miR-194.
Adenosine Triphosphate ; Anticonvulsants ; Deoxyglucose/pharmacology* ; Epilepsy/genetics* ; Glucose ; Humans ; MicroRNAs/genetics* ; Potassium Channels, Inwardly Rectifying/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction