“PHARMACOLOGICAL SCREENING OF A NOVEL CHITIN DERIVATIVE IN ALUMINIUM CHLORIDE INDUCED IMPAIRMENT OF LEARNING AND MEMORY”
Sharma Aarti* and Kothiyal Preeti
Objective: The marine environment is known as a rich source of bioactive chemical structures with promising biological activities such as neuroprotection. Based on several studies, it is reported that Chitin and its derivatives have remarkable potential as neuroprotective anti- Alzheimer`s agents owing to their anti amyloid, anticholinesterase, antioxidant and anti-inflammatory attributes. Chitin is one of the most abundant biopolymers in nature and the most widespread amino-polysaccharide. The present study was designed to assess the effect of Aminoethyl chitin, a water soluble novel chitin derivative on learning and memory in Aluminium chloride treated mice, brain cholinesterase (AchE) levels and on associated altered brain oxidative stress markers in aluminium chloride treated mice. Methods: The extract was administered orally in two doses (400, and 800 mg/kg p.o.) for a period of 30 days. Piracetam (Standard), 500mg/kg p.o., was used as a standard treatment. Aluminium chloride was administered daily in the dose of 4.2 mg/kg intraperitoneally, along with respective treatments. The Morris water maze, elevated plus maze and radial arm maze were used to assess cognitive functions. At the end of the study, effect of the drug was assessed on Acetyl cholinesterase and lipid per oxidation (TBARS analysis) in the brain tissue of mice. Histopathology was also used as a biomarker to assess toxic effects of aluminium chloride exposures in different groups. Results: Aluminium chloride treated group (Negative control) showed significantly impaired acquisition and retention of memory and neurodegeneration as compared to the normal saline treated group (Vehicle control). Pre-treatment with Amino ethyl chitin (400 and 800mg/kg p.o.) for 30 days significantly reversed Aluminium chloride induced amnesia and neurodegeneration, as evidenced by increase in the time spent in target quadrant (TSTQ) in Morris water maze, decreased transfer latency (TL) in elevated plus maze and increase in the number of correct choices made by the animal in the radial arm maze as compared to the Aluminium chloride treated group. Aluminium chloride administration also caused increase in AchE (Acetyl cholinesterase) activity and lipid per oxidation as compared to the standard and Amino ethyl chitin treated groups. Pretreatment with Amino ethyl chitin (400 and 800mg/kg) resulted in a significant decrease in Lipid per oxidation and AchE activity as compared to the Aluminium chloride treated group,in a dose dependent manner. Conclusion :These results suggest that Amino ethyl chitin induces improvement in learning and memory of amnesic mice and this effect may be attributed to a certain extent to decreased oxidative stress, reduction in brain AchE levels and neuroprotective property of the drug.
Keywords: Neurodegeneration, ?-Secretase, Amyloid Beta (A?), Neuroprotection Alzheimer?s, Amino ethyl chitin, Aluminium chloride.
[Full Text Article]