Chronic intrahippocampal administration of streptozotocin targeting insulin receptors induced memory loss in rats: A dose comparison study

Authors

Mazzura Wan Chik¹, Nurul Aqmar Mohamad Nor Hazalin², Gurmeet Kaur Surindar Singh^2,3*

¹Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam, Malaysia.
²Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam, Malaysia.
³Brain Degeneration and Therapeutics Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Malaysia.

Abstract

Streptozotocin (STZ) induced neurotoxicity via intracerebroventricular administration is currently used as one of the accepted rodent model that represents sporadic Alzheimer’s disease. The present study aimed to investigate the effects of different STZ concentrations on spatial memory performance of rats when injected directly into the hippocampal region of the brain in order to mimic the pathological aspects of human Alzheimer’s disease. Four months old Sprague-Dawley rats were divided into control (no treatment), two sham-operated (injected with 5 and 10 μl phosphate buffer saline respectively) and two STZ treatment groups (3 mg/kg bw; 5 μl and 6 mg/kg bw; 10 μl). STZ and vehicle were injected bilaterally as a single injection into the rats’ dorsal hippocampus. After 3 months of STZ administration, the level of cognitive impairment was assessed using the Morris water maze. Both STZ-treated groups showed significant impairment on the acquisition of spatial memory (escape latency and total distance travelled) and retrieval of spatial memory (time spent in the target quadrant). However, STZ administered at 6 mg/kg bw induced severe neurotoxicity as evidenced by mortality and destruction of the brain region at the injection site with presence of large lesions. Therefore, low dose of STZ (3 mg/kg bw) administered in the intrahippocampal is sufficient to demonstrate memory impairment that can be used as a suitable rodent Alzheimer’s disease model. These findings contribute in assisting researchers to decide the concentration of STZ to develop sporadic Alzheimer’s disease rat model for the studies on prevention, detection and possible cure for the disease.

Keywords: sporadic Alzheimers, rat model, intrahippocampal, streptozotocin, Morris water maze, brain insulin receptors.

PAGES:13-29

doi:10.24193/cbb.2018.22.02

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