Journal
PHARMACEUTICAL BIOLOGY
Volume 54, Issue 10, Pages 2211-2219Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/13880209.2016.1150306
Keywords
AMPK; BDNF; compound C; global cerebral ischaemia; passive avoidance task
Funding
- research council of Alborz Medical University
- Ahvaz Jundishapur University of medical sciences
Ask authors/readers for more resources
Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia. Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory. Materials and methods Rats were pretreated with metformin (200 mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured. Results Pretreatment with metformin (met) in the met + ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p<0.001) and increased latency time compared with the I/R group (p<0.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R + met group (p<0.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p<0.001) but increased that compared with the sham group (p<0.001). The level of pro-BDNF decreased in the met + CC + I/R group compared with the met + I/R group (p<0.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p<0.001). Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available