Effects of Metformin Microinjection into Lateral Ventricles on Memory Retention of Streptozotocin Rat Model of Sporadic Alzheimer's Disease

H. Haghdost[1], M.H. Esmaeili[2], M. Sofiabadi¹, S. Rastak[3], B. Heydari[4], Z. Charmchi⁴, L. Ghasemi⁵

Received: 23/09/2014      Sent for Revision: 26/11/2014      Received Revised Manuscript: 09/03/2015     Accepted: 08/04/2015

Background and Objective: Insulin regulates many important processes in the central nervous system such as synaptic plasticity, learning and memory. Experimental evidence suggest a link between type 2 diabetes and Alzheimer’s disease (AD). Insulin modulates the metabolism of beta-amyloid precursor protein in neurons, decreasing the intracellular accumulation of beta-amyloid. The aim of the present study was to investigate the effects of intraventricular injection of Metformin on memory retention in streptozotocin (STZ) rat model of Alzheimer's disease.

Materials and Methods: A total of 56 male wistar rats (200-250 gr) were divided into 7 groups (n=8): Control, Sham, STZ, STZ +Salin, STZ +Metformin. For induction of AD, STZ (3 mg/kg, i.c.v, 10 μl each) were administered bilaterally into latral ventricles. Two weeks later all rats were trained in one trial step-through passive avoidance learning.  Saline (5 ul) or Metformin (50,100,200ug/kg, 5 ul, i.c.v) were injected through the guide cannula immediately after training. Retention test was done two days later.

Results: Our results showed that post-training microinjection of Metformin into lateral ventricles improves memory retention in STZ rat model of AD in a dose dependent manner, so that the time spent in the light chamber before entering to the dark area in the STZ + Metformin (200ug/kg) group rats were significantly more than STZ group.

Conclusion:  The results indicated that Metformin is useful for treatment of Alzheimer's disease.

Key words: Alzheimer, Metformin, Intraventricular, Passive avoidance learning, Memory retention, Streptozotocin

Funding: This research was funded by Qazvine University of Medical Sciences.

Conflict of interest: None declared.

Ethical approval: The Ethics Committee of Qazvine University of Medical Scinces approved the study.

How to cite this article: Haghdost H, Esmaeili MH, Sofiabadi M, Rastak S, Heydari B, Charmchi Z, Ghasemi L. Effects of Metformin Microinjection into Lateral Ventricles on Memory Retention of Streptozotocin Rat Model of Sporadic Alzheimer's Disease.. J RafsanjanUniv Med Sci 2014; 14(3): 222-211. [Farsi]