Activation of JNK and p38 in rat hippocampus after kainic acid induced seizure

Kainic acid, an analogue of glutamate, causes limbic seizures and induces cell death in the rat brain. We examined the activation of MAPK family kinases; ERKs, JNKs and p38 kinase in rat hippocampus after KA treatment. Activation of all three kinases were observed at 30 min after the treatment, but, in contrary to ERK phosphorylation, which lasted up to 3 h, the phosphorylation of JNK and p38 returned to the basal level by 2 h. The phosphorylation of' upstream kinases for the MAPK family was distinct. The phosphorylation of MEK1 clearly increased at 30 min but diminished rapidly thereafter. The phosphorylation of MKK6 was also increased but reached peak at 2 h after KA treatment. However, the phosphorylation of other upstream kinases, SEK1 and MKK3, gradually decreased to 3 h after KA treatment. These results indicate that the KA activates all of the three MAPK family kinases with different time patterns and suggest the possibility that MKK3 and MKK6, and SEK1 may not be the upstream kinases for p38 and JNK in rat hippocampus.

Regulation of MAPK Activity by Seizure-induced MKP-1 in Rat Hippocampus / 신경정신의학

OBJECTIVES: Both electroconvulsive shock(ECS) and kainic acid-induced seizures activate mitogenactivated protein kinases(MAPKs)in rat hippocampus. They can also induce the expression of MAPK phosphatase-1(MKP-1)in rat hippocampus. MKP-1 is known as a specific MAPK deactivator. This study aimed to elucidate the role of MKP-1 in the deactivation of MAPKs in rat hippocampus. METHODS: In order to induce MKP-1 in the hippocampus, ECS was given to the rats. At the time points when MKP-1 was sufficiently induced, the second ECS was given to them and the subsequent phosphorylation or activation of MAPKs were measured in the hippocampus. A second group of rats were injected with kainic acid and the relationship between MKP-1 expression and MAPK phosphorylation was examined in their hippocampi. RESULTS: The expression of MKP-1 did not influence the phosphorylation or activation of MAPKs following ECS in rat hippocampus. Kainic acid-induced expression of MKP-1 did not significantly reduce the phosphorylation of MAPKs. CONCLUSION: MKP-1 did not play a significant role in the deactivation of MAPKs which were activated by ECS or kainic acid in rat hippocampus.

Developmental Changes in the Phosphorylation of CREB Following Electroconvulsive Shock in Rat Brain / 신경정신의학

OBJECTIVES: In order to understand the biological basis of neurodevelopmental perspectives of mental disorders, the authors investigated the developmental and regional changes in the phosphorylation of the transcription factor CREB following the electroconvulsive shock(ECS) in rat brain. METHODS: Rats of various age groups (7, 14, 21 days postnatal and adults) were given ECS and their hippocampi and cerebella were dissected at specified time points. The content of CREB and phosphorylated CREB were measured by immunoblot analysis. RESULTS: The amount of CREB increased in the hippocampus and decreased in the cerebellum according to the age. Baseline levels of CREB phosphorylation in both tissues were increased from postnatal 14 days, and it was proportional to the amount of CREB protein in the cerebellum. In the hippocampus, ECS increased the phosphorylation of CREB at postnatal 21 days, but in the cerebellum, ECS did not increased the phosphorylation of CREB in any age group. CONCLUSION: CREB mediated signal transduction pathways showed developmental and tissue-specific changes. ECS increased the phosphorylation of CREB in the hippocampus by postnatal 21 days, but not in the cerebellum. CREB activation is supposed to be related with the inducdion of c-fos after ECS in the hippocampus. However, the Ser-133 phosphorylation of CREB could not completely explain the developmental and tissue specificity of c-fos induction.

Stress Among Chinese, Korean-Chinese and Korean High School Students: A Transcultural Study / 신경정신의학

OBJECT: In order to examine the interaction mechanisms of electroconvulsive shock(ECS) and antipsychotic drug at the level of molecular biology, we observed the effect of chlorpromazine pre-treatment on the activation of mitogen activated protein kinase(MAPBD induced by electroconvulsive shock(ECS) in rat hippocampus. METHODS: Male Sprague-Dawley rats were divided into 2 groups. To the experimental group chlorpromazine(20mg/kg) was given intraperitoneally, 3nd to the control disliked water was given instead. Thirty minutes later, ECS was given and the hippocampus was dissected out 2 minutes thereafter. Immunoblotting with antiphosphotyrosine antibody was carried out, and the signal intensity at 42kDa band was quantitized using densitometer. The obtained result was compared by student t-test between the experimental and the control group. The absolute amount of MAPK was measured by immunoblotting with anti-MAPK antibody. RESULT: The tyrosine phosphorylation of MAPK reached peak at 2 minutes after ECS. However, in the chlorpromazine pre-treated group, the peak level of MAPK tyrosine phosphorylation was significantly attenuated(t= -3.12, df= 14, p=0.008) compared to the control. In contrast to this, the absolute amount of MAPK did not differ between the pretreated and the control group. CONCLUSION: Chlorpromazine attenuated the tyrosine phosphorylation of MAPK by ECS. This finding seems to be related to the fact that chlorpromazine pre-treatment changed the c-fos expression by ECS in rat brain. Antipsychotic drug and ECS might interact at the level of MAPK signal transduction system, and this might explained the observed synergistic elect of two treatment modality.