ABSTRACT
Objective To evaluate the role of group Ⅱ metabotropic glutamate receptors (mGluRs) in cognitive decline caused by multiple administrations of ketamine in mice and the relationship with hippocampal glycogen synthase kinase-3 beta (GSK-3β) expression.Methods Forty-five SPF healthy female C57BL/6 mice,aged 6-8 weeks,weighing 20-30 g,were randomized into 3 groups (n=15 each) using a random number table method:control group (group C),ketamine group (group K) and mGluR agonist LY354740 group (group L+K).In K and L+K groups,ketamine 30 mg/kg was intraperitoneally injected three times a day at an 30-min interval for 14 consecutive days.LY354740 was intraperitoneally injected at 30 min before the first injection of ketamine in group L+K.The equal volume of normal saline was given instead in group C.Morris water maze test was performed the day after the last administration.The mice were then sacrificed,and hippocampi were harvested to determine the expression of GSK3β,NR2A and postsynaptic density protein 95 (PSD95) by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the expression of GSK3β3 and NR2A was up-regulated,and the expression of PSD95 was down-regulated in group K (P＜0.05),and no significant change was found in the parameters mentioned above in group L+K (P＞0.05).Compared with group K,the escape latency was significantly shortened,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the expression of GSK3β and NR2A was down-regulated,and the expression of PSD95 was up-regulated in group L+K (P＜0.05).Conclusion Group Ⅱ mGluRs are involved in the process of cognitive decline caused by multiple administrations of ketamine in mice,which is associated with up-regulated expression of hippocampal GSK-3β.
ABSTRACT
Objective To evaluate the role of nuclear factor kappa B (NF-κB) in cognitive decline in aged mice with sepsis.Methods Forty-five SPF healthy aged female C57BL/6 mice,aged 10-12 months,weighing 20-30 g,were assigned into 3 groups (n=15 each) using a random number table:control group (group C),sepsis group (group Sep) and NF-κB selective inhibitor pyrrolidine dithiocarbamate (PDTC) group (group PDTC).Lipopolysaccharide 250 μg/kg was injected intraperitoneally once a day for 7 consecutive days in Sep and PDTC groups,and in addition PDTC 50 mg/kg was injected intraperitoneally at 30 min before lipopolysaccharide injection once a day for 7 consecutive days in group PDTC.The equal volume of normal saline was given in group C.Five mice in each group were sacrificed at 2 h after the last administration,cardiac puncture was performed and blood samples were collected,and then the mice were sacrificed and hippocampi were harvested for determination of the levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β) and IL-6 in plasma and hippocampal tissues using enzyme-linked immunosorbent assay.Cognitive function was assessed using open field,elevated plus maze and Morris water maze tests at 24 h after the last administration in the other mice left in each group.Results Compared with group C,the levels of TNF-α,IL-1β and IL-6 in plasma and hippocampal tissues were significantly increased,the time of movement at the central region was shortened,the percentage of time spent in the open arms and number of entries into the open and closed arms were decreased,the escape latency was prolonged,the time of staying at the original platform quadrant was shortened,and the frequency of crossing the platform was decreased in group Sep (P＜0.05).Compared with group Sep,the levels of TNF-α,IL-1β5 and IL-6 in plasma and hippocampal tissues were significantly decreased,the time of movement at the central region was prolonged,the percentage of time spent in the open arms and number of entries into the open and closed arms were increased,the escape latency was shortened,and the time of staying at the original platform quadrant was prolonged in group PDTC (P＜0.05).Conclusion NF-κB is involved in cognitive decline in aged mice with sepsis.