Effect and mechanism of acrylamide on learning and memory and long-term potential in female Wistar rats
10.3867/j.issn.1000-3002.2017.01.011
- VernacularTitle:丙烯酰胺对雌性Wistar大鼠学习记忆和长时程增强的影响及其可能机制
- Author:
Man ZHANG
;
Tao MENG
;
Wenjin ZHAO
;
Bin LI
- Keywords:
acrylamide;
step down test;
Morris water maze;
long-term potential
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(1):87-93
- CountryChina
- Language:Chinese
-
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.
