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Objective To investigate the effect of propofol post-conditioning on RNA2 (ADAR2)-α-amino-3-hydroxy-5-methyliso xazole-4-propionic acid (AMPA) receptor subunit glutamate 2 (GluR2) pathway in hippocampal neurons of fetal rats subjected to oxygen-glucose deprivation (OGD).Methods The hippocampal neurons were isolated from the fetal rats obtained from Wistar rats at 16-18 days of gestation and primarily cultured for 7 days.The primarily cultured neurons were randomly divided into 3 groups (n =6 each):control group (group C) ; OGD group (group O) ; propofol post-conditioning group (group P).The cells were subjected to OGD for 1 h followed by restoration of O2-glucose supply in group O.In group P,the cells were subjected to OGD for 1 h followed by restoration of O2-glucose supply and then 1.2 μg/ml propofol was added and the cells were cultured for 2 h and then the culture medium was replaced with plain culture medium.At 24 h of incubation,the cells were collected for assessement of the survival rates of the hippocampal neurons and for determination of the expression of ADAR2 mRNA (by RT-PCR),the total ADAR2 protein (tADAR2) and ADAR2 protein in the nucleus of cells (nADAR2) (by Western bolt).The editing percentage of GluR mRNA at the Q/R site was analyzed by nest RT-PCR and BbV1.Results There was no significant difference in the expression of ADAR2 mRNA and tADAR2 among the three groups.Compared with group C,the survival rates of the hippocampal neurons were significantly decreased,the expression of nADAR2 was down-regulated,the ratio of nADAR2/tADAR2 was decreased,and the editing percentage of GluR mRNA at the Q/R site was decreased in group O.Compared with group O,the survival rates of the hippocampal neurons were significantly increased,the expression of nADAR2 was up-regulated,the ratio of nADAR2/tADAR2 was increased,and the editing percentage of GluR mRNA at the Q/R site was increased in group P.Conclusion Propofol post-conditioning reduces OGD-induced damage to hippocampal neurons of fetal rats through activating ADAR2-AMPA receptor GluR2 pathway.
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ObjectiveTo explore the intervention effect and the underlying molecular mechanism of 3-Methyladenine on behavioral damage of neonatal rat with prolonged seizures. MethodsForty-five 6-dayold SD rats were randomly ( random number) divided into the recurrent prolonged neonatal seizure group ( RS group), the 3-MA-treated seizure group and control group. The volatile agent flurothyl was used to induce 30 min seizure attack. At postnatal day 6 (P6), recurrent seizures were induced once daily for successive 6 days in both RS group and 3-MA group. In 3-MA group, 3-MA (2 μL) was injected daily before seizures induced.Neural-behavior changes were observed with double-blind method including swimming development, open field test and Morris water maze analysis. Bcl-2 and Beclinl protein levels in hippocampus were detected by western blot method at P50. ResultsThe total scores of swimming behavior in RS rats were decreased significantly compared with those of control and 3-MA rats ( control: 7. 44 ±1. 13, RS: 5.06±1.63, 3-MA: 7.33 ±1.08, F=16.19, P＜0. 01) . The start-latency time of open filed behavior in RS rats ( 13. 33 ±6. 69) were increased significantly compared with that of control (7. 11 ±2. 37) and 3-MA rats (9. 91 ±4. 23) (F=4. 39, P＜0. 05). The escape latency was significantly longer in rats of RS group than that of control and 3-MA rats on the 4th and 5th days (P ＜ 0.05). The level of Bcl-2 in hippocampus of RS group (0. 587 +0. 139) were significantly lower than that of control (0. 782 +0. 083) and 3-MA groups (0. 799 + 0. 163) (F =4. 7 1, P ＜ 0. 05 ). There were no significant differences in the level of Beclin1 protein in hippocampus among the three groups ( F =0. 27, P ＞ 0. 05 ).Conclusions Pretreatment with autophagy inhibitor 3-MA in acute phase of neonatal seizures could significantly improve neurobehavioral capacity, which might be associated with the increased in the level of Bcl-2 protein in hippocampus.
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Objective To investigate the tracking neurofibra pathway from the hippocamlpal neurons to septal nucleus,and to explore the effects and mechanisms of ghrelin on the learning and memory in septal nucleus lesion rats.Methods Retrogradely tracing method was used to observe Fluorogold (FG) reaching sites in hippocampus.The septal nucleus was destructed by direct current using stereotactic technique.Step-down test and morris water maze were used to test the effects of learning and memory ability by means of microinjecting ghrelin into hippocampal CA1 area in rats.Results After injection of FG into septal nucleus,retrogradely labeled neurons and neurofibra were found in the hippocampal neurons with FG.Ghrelin injection of hippocampal CAI area could promoter learning and memory ability in rats.It showed that the escaped latent period was significantly lengthened ( (3.2 ± 0.9) s vs (6.9 ± 1.1 ) s,P ＜ 0.05) and the wrong numbers in 5 min were obviously decreased in escape response test; and the latency of looking for the plat was significantly shorter in morris water maze test ( 1.8 ±0.4vs 0.8 ± 0.1,P ＜ 0.05 ).However the effects above-mentioned on learning and memory was significantly weak after septal nucleus lesioning.It showed that the escaped latent period was markedly shortened ( ( 19.5 ±3.2)s vs ( 10.5 ± 2.1 ) s,P ＜ 0.05 ) and the wrong numbers in 5 min were obviously increased ( ( 3.9 ± 0.8 ) s vs ( 1.8 ±0.5 ) s,P＜0.05 ) in escape response test.The latency of looking for the plat was significantly lengthened in morris water maze (P＜0.05).Conclusion Ghrelin could elevate the learning and memory ability in hippocampus,and the effects may be related to the septal-hippecampus pathway.
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Objective To compare the differences of cognitive dysfunction and hippocampal atrophy among patients with temporal lobe epilepsy (TLE) and healthy controls and probe into the relativity of cognitive dysfunction with hippocampal atrophy after temporal lobe epilepsy. Methods Forty-nine TLE cases and 20 healthy individuals were randomly selected. The WAMS-R and WAIS-R scales were adopted to assess the memory and intelligence of all the subjects. Hippocampal volumes were measured by semiautomatic measurement on the head magnetic resonance imaging (MRI). The degree of hippocampal atrophy (DHA) and asymmetry index (AsI) were caculated by adjusting hippocampal volumes and ratio of difference of two lateral hippocampal volumes. Results Compared with the healthy controls, not only did the TLE patients exhibit more memory deficits (83.2±21.0,t=-3.365 ,P=0.001 ), but also more fullscale intelligence (91.0±12.3, t=- 4.291, P=0.000). The bilateral hippocampi of all TLE patients significantly decreased in volume ( P=0.000 ) and increased in AsI ( t=3.975, P=0.000 ). The MQ of TLE patients was significantly negatively related to the duration of the illness ( r=-0.339, P=0.017 ). The bilateral DHA and the hippocampal AsI were negatively related to Z scores (left: r=-0.297, P= 0.038, right: r=-0.305, P=0.033, AsI: r=-0.441, P=0.002), repectively. Conclusions The more the DHA and asymmetry of bilateral hippocampi, the worse the cognitive dysfunction. The quantitative measurements of hippocampal volume could be used as a clinically effective factor for evaluating the decrease of the intelligence of TLE patients.