Evaluation of Neuroprotective Activity of Felodipine on Streptozotocin Induced Alzheimer's In Rats

Abstract

Background and objective Alzheimer’s disease (AD) is a mental impairment and chronic neurodegenerative disease characterized by progressive decline in memory, coordination and loss of other cognitive functions. AD represents 60% to 80% of pronounced cases of age-related dementia. This age dependent illness is affiliated with extracellular amyloid plaques accumulation and twisted Neurofibrillary tangles. An introduced approach in the therapeutics of Alzheimer’s is calcium channel blockers (CCBs). Calcium channel blockers hinder AD cells from Aβ oligomer production by prohibiting Ca2+ influx through closure of L-type calcium channels and thus intervene with calcium signaling which is involved in amyloid toxicity. Calcium channel blockers also arrest the protraction of inflammatory mediators such as NO, tumor necrosis factor (TNF)-α and interleukin-1 (IL-1) and mitigate oxidative stress. Thus, calcium channel blockers can prove to enhance general cognition on the basis of their ability to reverse experimentally induced amnesia and improve learning and memory in young adult animals. Material and Methods The Alzheimer’s dementia like conditions were generated in the Disease control (DC) group with the induction of stz (3mg/kg) by ICV route by surgery using a stereotaxic apparatus. The treatment groups were exposed to Donepezil (5mg/kg) and Felodpine (1and 2.5mg/kg). Donepezil (5mg/kg) (cholinesterase inhibitor) was used as a standard treatment. To evaluate the dementia and behavior in the animals Y-maze and water maze were carried out, For Y maze animals were trained prior to treatment and after the period of 30 days again the behavior was evaluated for all the groups, whereas in water maze the animals were given training and evaluated for their behavior after completion of treatment. After the behavioral parameters animals were sacrificed. The brain tissue was subjected to the analysis of oxidative stress parameters, acetyl cholinesterase assay, and total protein estimation. Histopathological studies were also carried out. Y-maze: Total arm entry: The results of total arm entry give the significant decline in the disease control group compared to Normal control. Whereas in the Felodpine treated groups there was significant elevation in the total no. of entries as compared to DC and SHAM group. Morris water maze: - There was significant decline in time spent in target quadrant and increased escape latency in DC group when compared with NC. But Felodpine treated groups on probe trail reveled significant reduction in escape latency time. Acetyl cholinesterase assay: There was marked decline in the levels of cholinesterase in the Felodpine group as compared to the disease control group but the difference was found to be insignificant for Felodpine (2.5mg/kg). Total Protein Estimation: The investigation showed the rise in the A-beta and hyper phosphorylated tau protein in the DC group whereas those were found to be decline in the treated groups but changes found were not that significant. Oxidative stress parameters: The MDA levels were found to be significantly elevated in the disease control group as compared to normal. It was found to be lowered in the Felodpine group as compared to the DC group. SOD, GSH levels were significantly reduced in the DC group as compared to the NC. In the Felodpine group there was significant increase in the SOD, GSH. Histopathological evaluation: - The alignment of the granular cells and pyramidal glial cells was found to be disturbed in DC group as compared to NC. The cell death was observed in the sub granular zone in DC while the arrangement of cell was intact with no cell death and no neurodegeneration in the NC and the treated groups. Also these groups showed decline in amyloid aggregation and fibrils.

Conclusion The study showed that Streptozotocin (STZ) as an inducing agent produces neurodegeneration and is responsible to produce hallmarks of sporadic AD. Administration of STZ causes impairment in cognitive skills and memory debt which can be concluded through neuro behavioral evaluation and other biochemical estimations with histopathological studies. On the other hand, animals treated with Donepezil and Felodpine (1mg/kg) are found to show Neuroprotective effects when compared to STZ induced animals. Therefore, from results of behavioral parameters and biochemical investigations it could be concluded that Felodpine prevents memory impairment in rat model and can be attributable for amelioration of cognitive deficits and amyloid defects.