The Expression Of DISC1 Protein In The Focal Cortical Dysplasia Associated With Refractory Epilepsy In Patients Of Children

Epilepsy is a chronic brain disease of central nervous system. It is one of seriously chronic diseases to harm human health. It is also one of the most common childhood neurological disorders, and the rate of which was 0.3%~0.6%.It results in serious burden of mind and economy to the society, family and one person. So the epilepsy is to be paid more attention to a kind of diseases in the central nervous system. In recent years, though the study of epilepsy has made great progress in many ways, but its pathogenesis is still not very clear.At present, there are about 10 million patients with epilepsy and nearly 1 million annually. About of one-third of whose patients with epilepsy has developed eventually to drug refractory epilepsy in our country. Temporal lobe epilepsy is an important type of intractable epilepsy. The focal cortical dysplasia is one of the main factors.FCD is a type of cortical malformations. It is closely related to proliferation, migration and organization of early neurons during embryonic development.2011 International League Against Epilepsy latest has divided focal cortical dysplasia into three types: FCD type â… , FCD type â…¡ and FCD type â…¢. FCD type â…  and â…¡are the simple type of FCD.FCD type â…¢ is a newly added type, which is bound FCD. It refers to abnormal cortical layering a liability associated with diseases. It is divided into four subtypes: FCD type â…¢a is associated with hippocampal sclerosis.FCD type â…¢b is associated with tumors, FCD type â…¢c is related to vascular malformations. And FCD type â…¢d is associated with other liability lesions got early years ago.AKT protein is known as protein kinase B(PKB), a serine/threonine protein kinases.AKT protein has gradually been widely recognized during studying the relationship between epilepsy and m TOR signaling pathway. There are two major signaling pathways, such as PDK1/AKT/m TOR and PI3K/AKT/m TOR. Whether a number of studies in animal or human have confirmed that expression of AKT protein was significantly increased in epilepsy pathological tissues. Foreign researches have shown that Disruptedin-schizophrenia 1 inhibits expression of AKT protein.DISC1 is an important candidate gene for mental illness, which is a common risk factor for schizophrenia, bipolar disorder, depression, autism and Asperger syndrome. Many genetic studies have indicated that DISC1 is not merely disrupted-in-schizophrenia, but is more generally implicated in various brain dysfunctions associated with aberrant neural development and intracellular signaling pathways. At present, the study of DISC1 in the role of central nervous system mainly concentrates on neurons and synapses development: a mature neurons, proliferation, migration, positioning, differentiation, dendritic growth and synaptic plasticity.DISC1 encodes DISC1 protein.DISC1 protein is a multifunctional scaffold protein, which plays an important role in the adult brain, especially in the neural occurrence and development of dentate gyrus. Partial patients with epilepsy have performance of Cognitive impairment and mental disorder, which is similar with mental illness. DISC1 is expected to become a therapeutic target of mental illness and epilepsy. So it is particularly important to research the pathogenesis of focal cortical dysplasia associated with refractory epilepsy about DISC1 and AKT protein.This paper intends to study the following two aspects.Part1 The expression of DISC1 in the hippocampus of temporal lobe epilepsy patients with different mental status in childrenObjective: To analysis expression of Disrupted-in-schizophrenia 1 protein in the hippocampus of temporal lobe epilepsy with different mental status in children. To investigate the impact of DISC1 on mental status and cognitive function in patients with epilepsy.Methods:Surgically resected specimens, which were diagnosed as temporal lobe epilepsy pathology, from 26 children patients with temporal lobe epilepsy treated at the functional neurosurgery department of the HE BEI General Hospital between 2006 and 2013 were retrospectively chosen for this study from archival paraffin blocks. There are 16 patients in normal mental status, and 10 patients in the abnormal among them. Using Conventional HE staining, immunohistochemical methods and Western-blot technique for detecting the expression of DISC1 protein in the brain tissue. Results:1 DISC1 protein located within nucleus and cytoplasm of hippocampal neurons, mainly in cytoplasm.2 The expression of DISC1 protein of children patients with temporal lobe epilepsy in abnormal mental status was less than the normal mental status(P<0.05).Conclusion: The expression of DISC1 protein decreased in the abnormal group, compared with the normal mental status group, indicating that DISC1 protein may be associated with cognition and mental status of patients with temporal lobe epilepsy.Part2 The expression of DISC1 and AKT protein in temporal cortex of children with focal cortical dysplasia type â…¢aObjective:To observe the possible mechanism of DISC1 and AKT protein expression changing in FCD â…¢a with temporal lobe epilepsy in children, through detecting the DISC1 and AKT protein expression in focal cortical dysplasia(FCD) â…¢a with temporal lobe epilepsy of children.Methods:Using immunohistochemistry, to detect the expression of DISC1 and AKT protein in children patients with FCD â…¢a related with temporal lobe epilepsy.Results:1 DISC1 and AKT immunohistochemistry positive staining mainly located in the cytoplasm and nucleus of neurons, mainly in the cytoplasm. And the former was also expressed in the glial cells.2 Compared with the normal control group, the expression of DISC1 and AKT proteins in FCD â…¢a type of temporal lobe epilepsy in children were also different, and the differences were statistically significant(P<0.01).Conclusion:1 DISC1 protein expression was significantly decreased in children with FCD â…¢a type of temporal lobe. In contrast, expression of AKT protein significantly increased. This suggested that the changes in DISC1 and AKT protein might be involved in the process of FCD type â…¢a with temporal lobe epilepsy of children.2 The relation of DISC1 and AKT protein expression in children with temporal lobe FCD â…¢a was negative. The result suggested that decreased expression of DISC1 protein, so the role of which in inhibiting the expression of AKT protein is impaired. This may be a pathogenesis of FCD â…¢a related with temporal lobe epilepsy.