Alzheimer's disease is a brain ailment that causes cell degradation and is the leading cause of dementia, which is defined by a deterioration in thinking and independence in routine everyday activities. Insulin possesses neuroprotective and memory-enhancing effects indicating a permissive function for insulin in cognition. Defective insulin signaling promotes Aβ aggregation and accelerates Aβ formation in the brain. Based on this evidence, Alzheimer's is also defined as diabetes of the brain or Type 3 Diabetes. Diabetes was induced in mice by Alloxan (100mg/kg) and sucrose 35% solution. Glucose level was monitored, and test drugs were given accordingly. Behavioral models employed in the current study were elevated plus maze, morris water maze, actophotometer, and novel object recognition test. Biochemicals performed were all mitochondrial complexes, glutathione level, protein carbonyl level, lipid peroxidase, and acetylcholinesterase activity. Histopathological evaluation of the hippocampal region was carried out under a bright field microscope. Alloxan administration produced significant hyperglycemia characterized by a significant increase in serum glucose level as compared to the naïve. During the acquisition test (learning), alloxan-treated mice significantly delayed the escape latency period to reach the submerged platform as compared to the naïve group. However, quercetin and naringenin administration significantly improved memory performance. In novel object recognition, alloxan treated spent more time near the familiar object, and the treatment group spent more time near the novel object. Alloxan treatment also disrupted the mitochondrial levels and lowered the antioxidant enzyme levels, whereas the treatment group significantly reversed the changes. In the present study, alloxan administration caused significant impairment in cognitive behavior as evidenced by the Morris water maze (MWM) test, increased fasting blood glucose oxidative stress [through alteration of endogenous antioxidant markers i.e. superoxide dismutase (SOD), and catalase antioxidant enzyme activity and reduced glutathione (GSH) levels and oxidative stress markers i.e. reactive oxygen species (ROS) and protein carbonyls levels] and increased acetylcholinesterase activity in different areas of the brain (frontal cortex and hippocampus). Administration of quercetin and naringenin in different doses significantly reversed alloxan administration-induced behavioral, biochemical, and cellular alteration in both the frontal cortex as well as in hippocampus.
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