ABSTRACT
OBJECTIVE To investigate the accumulated effect and the mechanism of repeated sc administration of acrylamide (AM) on learning and memory after 28 d,and the effect of AM on the amplitude of population spike(PS) potential after a single sc administration of AM. METHODS Female Wistar rats were sc adminstered with AM 10, 20 and 40 mg · kg-1 once a day for 28 d, and weighted every week. The ability of study and memory was evaluated, The morris water maze was used from 22nd to 28th day,followed by step down test on the 29th and 30th day. The escape latent period and the number of errors in those two days were recorded. Rats from normal control group and AM 40 mg·kg-1 group were taken to have their N-methyl-D-aspartate receptor (NR) and calmodulin-dependent protein kinaseⅡ (CaMKⅡ) protein levels detected by Western blotting. Additionally, some other female Wistar rats were sc administered with a single dose of AM 40 mg · kg-1 ,before the changes in PS potential amplitude induced by high frequency stimulation were recorded by long-term potential (LTP). RESULTS Compared with normal control group, the relative body mass gain was significantly decreased in AM exposure groups(P<0.01). Additionally, the escape latency period was significantly increased in AM 20 and 40 mg·kg-1 groups compared with normal control group, while the crossing frequency was not significantly different betmeen these four groups. Compared with the first day of step down test, the number of errors was significantly decreased(P<0.01) and the escape latency period was significantly extended(P<0.01) in normal control group on the 2nd day. However, the number of errors and the escape latency period did not significantly change in the AM groups between the two days. The results of Western blotting showed that the protein expressions and phosphorylation of NR2A and NR2B, as well as the phosphorylation of CaMKⅡ in AM 40 mg · kg-1 group were significantly increased compared with normal control group. LTP result showed that AM 40 mg·kg-1 significantly inhibited the amplitude of PS potential after a single percutaneous administration. CONCLUSION AM can inhibit the PS amplitude by inhibiting the release of glutamate, increasing the expressions and activities of NR,and inhibiting PS potential, thus affecting the hippocampal synaptic plasticity, and the function of learning and memory.
ABSTRACT
The effects of glutamate transporters on synaptic plasticity in rat models of pilocarpine-induced status epilepticus were investigated. Male Wista rats ((304.06?13.79) g) were randomly divided into 5 groups, short-term seizures (SE) and its control (SC), long-term seizures (LE) and its control(LC), normal control (Sham) groups. Epilepsy rat models were induced by injection of pilocarpine(25 mg/kg, i.d.). Glutamate transporter inhibitor, DL-threo-benzyloxyaspartate (TBOA, 7.5 nmol,1 ?l) was microinjected into right side of hippocampus after 14 days of initial status epilepticus in SE and LE groups. The same volumes of artificial cerebrospinal fluid were injected into same side of hippocampus in SC and LC groups. Electroencephalographys (EEG) were detected in SE and SC groups after 2 h of drug injection. Long term potential (LTP) at perforant pathway and dentate gyrus(PP-DG) and EEG were recorded in LE and LC groups after two weeks of drug injection. Example of Fluoro-Jade-B staining in the rat brain was made at the end of electrophysiological experiment. The results showed that there was a significant decrease in theta band power of EEG in SE group compared with that of SC group (P 0.05). The slope of excitatory postsynaptic potential (EPSP) was significantly increased in LE group compared with that of LC group (P