الفهرس 
Title : The Possible Role of Insulin Resistance in Brain Changes Induced by Experimental Aging in Rats: Modulatory Effect of Certain Anti- Diabetics
AbstractOnly 14 pages are availabe for public view
 |  | from | 179 |  |  |
| | | from | 179 | | |
Abstract
Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggests that impaired insulin signaling is the major contributor in the development of Alzheimer{u2019}s dementia (AD), which is the most common type of senile dementia. In the present study, the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents was investigated, utilizing a rat model of brain aging and AD by the administration of D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days). Six groups of adult male wistar rats were used: Normal, D-gal, Met (500 mg/kg/day, p.o.), and Saxa (1 mg/kg/day, p.o.) control groups, as well as D-gal/Met and D-gal/Sax treated groups. Impaired learning and memory function was observed in rats treated with D-gal using Morris water maze test. Biochemical and histopathological findings revealed decreased content of acetylcholine and glutamate, while phosphorylated tau levels were increased accompanied by the deposition of amyloid plaques and neurofibrillary tangles all of which are characteristic changes of AD in the brain. Induction of insulin resistance in experimentally aged rats was evidenced by increased blood glycated hemoglobin, brain contents of insulin and receptors for advanced glycated end-products, as well as decreased brain insulin receptors level. Elevation of oxidative stress markers and TNF-Ü brain content was also demonstrated. Met and Saxa, with a preference to Met, restored the normal memory and learning functions in rats, improved D-gal-induced state of insulin resistance, oxidative stress and inflammation, and ameliorated the AD biochemical and histopathological alterations in brain tissues. Findings revealed in the study at hand suggest the involvement of insulin-sensitizing drugs like Met and Saxa in the alleviation of insulin resistance as the underlying pathology of AD and hence their potential use as promising anti-dementia drugs