Necroptosis mediates chemical hypoxia-induced injury andinflammation in HT22 hippocampal cells / 中国药理学通报

Aim To investigate whether necroptosis mediates chemical hypoxia-induced HT22 mouse hippocampal cell injury and inflammation.Methods HT22 hippocampal cells were exposed to cobalt chloride (CoCl2) to establish a model of the chemical hypoxia-induced injury and inflammation.The expression level of RIP3 (an index of necroptosis) was determined by Western blot.Cell counter kit-8 (CCK-8) assay was used to test the cell viability.Lactate dehydrogenase (LDH) activity in the culture medium was measured with commercial kits.Mitochondrial membrane potential (MMP) was examined by rhodamine123 staining followed by photofluorography.The intracellular level of reactive oxygen species (ROS) was detected by 2', 7'-dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The secretion levels of interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-α) were measured by ELISA.Results Treatment of HT22 hippocampal cells with 600 μmol·L-1 CoCl2 for 36 h markedly induced cytotoxicity, leading to a decrease in cell viability to (52.0±2.65) % , indicating that chemical hypoxia-induced cellular injury model was successfully set up.Besides, CoCl2 induced considerable injuries and inflammation, evidenced by increases in LDH activity, ROS production, MMP loss, as well as the secretion levels of IL-1β and TNF-α.Co-treatment of the cells with 40~100 μmol·L-1 Nec-1 (a specific inhibitor of necroptosis) and CoCl2 markedly attenuated the decrease in viability induced by CoCl2, reaching the best anti-cytotoxicity inhibitory effect at 80 μmol·L-1.Meanwhile, the co-treatment with 80 μmol·L-1 Nec-1 blocked the above injuries and inflammatory response induced by CoCl2.In addition, treatment of HT22 hippocampal cells for 6~48 h up-regulated the expression of RIP3, and Nec-1 alleviated the up-regulation of RIP3 expression level induced by CoCl2.Conclusion Necroptosis mediates chemical hypoxia-induced HT22 hippocampal cell injury and inflammation.

Corticosterone impairs reconsolidation of novel object recognition memory in rats / 中国组织工程研究

BACKGROUND: The formation of long-term memory includes acquisition, consolidation and reconsolidation. Reconsolidation is very important for the new memory transforming into stable memory. Stress is an important environmental factor in the process of learning and memory. Corticosterone is very important for stress response. At present, research about the impact of corticosterone on reconsolidation of novel object recognition memory is less. Thus, it is very important to test the impact of corticosterone on reconsolidation of novel object recognition memory in rats. OBJECTIVE: To analyze the effects of corticosterone on the reconsolidation of novel object recognition memory in rats. METHODS: (1) The rats were intraperitoneal y injected with corticosterone (0.1, 1 and 3 mg/kg) immediately after reactivation. The discrimination index was used to assess memory performance and calculated as the difference in time exploring the novel and familiar objects. (2) The rats were intraperitoneal y injected with corticosterone (3 mg/kg) 6 hours after reactivation. The discrimination index was used to assess memory performance and calculated as the difference in time exploring the novel and familiar objects. (3) The rats were intraperitoneal y injected with corticosterone 3 mg/kg without reactivation. The discrimination index was used to assess memory performance and calculated as the difference in time exploring the novel and familiar objects. RESULTS AND CONCLUSION: Immediate injection of corticosterone 3 mg/kg after reactivation significantly decreased the discrimination index. At 6 hours after reactivation or without reactivation, corticosterone administration did not impact the discrimination index. These results confirmed that corticosterone administration immediately after reactivation impairs the reconsolidation of novel object recognition memory. The damage effect depends on the reactivation experience and the specific time window after reactivation.

Current Research Progress of Apelin-13 / 天津医药

Apelin is a polypeptide consisting of 77 amino acids. Apelin receptors are found to be the angiotensin-like G protein coupled receptor (APJ). Apelin/APJ system is widely distributed in the peripheral and central nervous system. Apelin-13 is one of the subtypes of Apelin, which has strong biological activity. This study reviewed the new research prog?ress of Apelin-13 on physiological and pathological processes involved in the cardiovascular system, respiratory system, ner?vous system, digestive system and endocrine system.

Effect of nitric oxide synthase inhibitor L-NAME on fear extinction in rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of nitric oxide synthase inhibitor L-NAME on two tone fear extinction design in rats.Methods In AAA design,the rats received fear conditioning,extinction training and extinction test in the same context.In AAB design,the rats received fear conditioning and extinction training in context A,extinction test in context B.In each task,40 male rats were randomly divided into 4 groups (n =10 per group),and L-NAME(10,20 and 40 mg/kg) or saline was injected intraperitoneally (i.p) 30 min prior to extinction training.Percent freezing was used as an index for fear memory during extinction test phases.Further experiments were used to test state-dependency effects or nonspecific changes of locomotor activity that followed L-NAME injection.Results In AAA design,percent freezing was (27.42 ± 6.52) ％ in saline group,and (30.83 ±7.15) ％,(32.49 ± 8.55) ％,(38.94 ± 11.48) ％ in 10,20,40 mg/kg L-NAME group respectively.There was no significant difference in the level of percent freezing among the four groups (P＞0.05).In AAB design,percent freezing was (30.32 ± 6.15) ％ in saline group,and (32.83 ± 6.64) ％,(39.49 ± 8.74) ％,(49.94 ± 10.83) ％in 10,20,40 mg/kg L-NAME group respectively.Compared with saline,only rats with L-NAME 40 mg/kg showed more levels of freezing (P ＜0.01).In state-dependency effects test,compared with Sal-Sal group ((26.73 ±5.62) ％) which received both saline injections 30 min before extinction training and extinction test,respectively,both NAME-Sal group((48.44 ± 10.46) ％) and NAME-NAME group((61.25 ± 13.24) ％) showed more levels of freezing (P＜0.01,respectively).Conclusion These results show that L-NAME produces a task-dependent impairment of fear extinction,and implies that nitric oxide signaling is involved in memory process of certain extinction tasks.

Chronic nicotine enhances contextual fear memory in rats / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of chronic nicotine on contextual fear memory in rats.@*METHODS@#Rats were subcutaneously injected saline or nicotine for 14 days continuously to induce nicotine dependence. Somatic signs of spontaneous nicotine withdrawal were assessed on day 1 and 14 after the last injection. Locomotor activity was tested 13 days after the last injection. Contextual fear conditioning task was run 14 days after the last injection, which included 3 phases: habituation, fear conditioning, and test. Percent freezing was used as an index for fear memory during the conditioning and test phases. Finally, footshock sensitivity test was conducted.@*RESULTS@#Compared with the saline group, the global withdrawal scores significantly increased in the nicotine group when the somatic signs were assessed 1 day after the nicotine injection, while there was almost no difference in the 2 groups 14 days after the last injection. In the contextual task, the nicotine group showed a significant increase in the level of freezing response during the test phase but not in the conditioning phase. There was no significant difference in the locomotor activity and footshock sensitivity between the 2 groups.@*CONCLUSION@#Chronic nicotine enhances the contextual fear memory in rats. This effect is not attributed to the change of somatic signs, locomotor activity or footshock sensitivity.