Brain Insulin Resistance: Targeting PI3K/AKT/GSK3 Pathway In Intra Cerebroventricular Streptozocin Induced Rat Model Of Alzheimers Disease | 96424
Journal of Alzheimers Disease & Parkinsonism
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Alzheimer???s disease featuring dementia, cognitive deficits and behavioral alterations is one of the most common prevalent
neurodegenerative diseases affecting majorly elderly people termed as sporadic AD. Global prevalence of AD is sharply
increasing, expected to affect almost 115 million people by 2050. Down-regulation of insulin signaling pathway of PI3KAKT
plays a significant role in the pathophysiology of AD. Intra cerebroventricular streptozocin is used for the model of
sporadic Alzheimer???s disease being established. Animals are divided into various groups comprising normal control, sham
control, diseased and drug treated groups. Protocol lasts for 21 days, sacrificing animals on 22nd day followed by isolation of
serum and dissection of cortex and hippocampus, preserving the same for further analysis. Behavioral studies, biochemical
estimations and molecular techniques are done for evaluating several parameters of control, diseased and treated groups of
animals. Behavioral studies like Morris water maze, novel object recognition and actophotometer are performed for cognition,
memory and locomotor activity. Biochemical estimations for antioxidant activity are performed as glutathione reductase assay,
catalase assay, glutathione S-transferase assay, lipid peroxidation assay, superoxide dismutase assay and protein carbonylation
assay. Protein concentrations are determined by biuret method. Cholinergic activity is determined by acetylcholinesterase
assay. Inflammatory cytokines like TNF-?, IL-6 is determined by ELISA method. Mitochondrial dysfunction is evaluated
estimating mitochondrial enzyme complex 1, 2, 3 and 4. Histopathology is done. Molecular techniques like western blotting
for Akt protein and RT-PCR for PI3-K, AKT, p-AKT, NF-?? and GSK 3-? is performed for gene expression analysis.
Ansab Akhtar has received his BPharma from Jamia Hamdard University and MS degree from NIPER, Hyderabad. Currently he is pursuing his PhD in Pharmacology from University Institute of Pharmaceutical Sciences Panjab University, Chandigarh, India.