Abstract:OBJECTIVE: To explore the molecular mechanism of brain protection against convulsive brain damage in premature brains by observing the changes of apoptotic-regulating genes of bcl-2 and c-Jun expression in the hippocampus in Wistar rats with different ages after status convulsion (SC). METHODS: SC was induced in infant Wistar rats (IRs) and adult Wistar rats (ARs) by intraperitoneal injection of lithium-pilocarpine. The rats were sacrificed at 3 hrs, 6 hrs, 12 hrs, 1 day, 3 days and 7 days after SC (n=8). Bcl-2 and c-Jun protein and mRNA levels were measured using immunocytochemistry, RT-PCR and in situ hybridization. RESULTS: c-Jun protein levels increased significantly at 3 hrs and reached the peak at 6 hrs after SC in both IRs and ARs compared to those in the normal control group (P<0.01). c-Jun protein levels started to decrease 12 hrs after SC in both IRs and ARs. The expression of c-Jun protein in IRs returned to the basal level 1 day after SC, while remained higher in ARs than in the normal control group by 7 days after SC. The expression of c-Jun protein in ARs was much higher than that in IRs from 6 hrs to 7 days after SC (P<0.05). c-Jun mRNA level was in parallel with the protein level as mentioned in IRs and ARs after SC. There were no changes observed in both bcl-2 protein and bcl-2 mRNA levels after SC in IRs and ARs. CONCLUSIONS: SC may induce an up-regulation of proapoptotic gene c-Jun in the hippocampus after SC, with a less strong extent and shorter duration in IRs compared to that in ARs. This might be one mechanism of brain protection against convulsive brain damage in IRs. The expression of bcl-2 remains unchanged after SC and is not affected by age in both IRs and ARs.
YUAN Ai-Yun,JIANG Li,ZHANG Xiao-Ping. Differences of apoptotic-regulating gene expression in the hippocampus in rats with different ages after status convulsion[J]. CJCP, 2011, 13(5): 411-414.
[5]Setkowicz Z, Janeczko K. Long-term changes in susceptibility to pilocarpine-induced status epilepticus following neocortical injuries in the rat at different developmental stages[J].Epilepsy Res, 2003, 53(3): 216-224.
[7]Eilers A, Whitfield J, Vekrellis K, Neame SJ, Shah B, Ham J. c-Jun and Bax: regulators of programmed cell death in developing neurons[J]. Biochem Soc Trans, 1999, 27(6): 790-797.
[8]Szot P, White SS, Shen DD, Anderson GD . Valproic acid, but not lamotrigine, suppresses seizure-induced c-fos and c-Jun mRNA expression[J]. Brain Res Mol Brain Res, 2005, 135(1-2): 285-289.
[9]Storey TW, Rho JM, White SS, Sankar R, Szot P. Age-dependent differences in flurothyl-induced c-fos and c-Jun mRNA expression in the mouse brain[J]. Dev Neurosci, 2002, 24(4): 294-299.
[10]Gross A. Bc1-2 proteins: regulators of the mitochondrial apoptotic program[J]. IUBMB Life, 2001, 52(3-5): 231-236.
[11]Henshall DC, Simon RP. Epilepsy and apoptosis pathways[J]. J Cereb Blood Flow Metab, 2005, 25(12): 1557-1572.