Evaluation of Memory Enhancer in Scopolamine-Induced Cognitive Deficit Mice Model

Evaluation of Memory Enhancer in Scopolamine-Induced Cognitive Deficit Mice Model

Introduction

Cognitive impairment and memory loss are hallmark features of neurodegenerative disorders such as Alzheimer’s disease. To explore potential therapeutic interventions, preclinical animal models play a crucial role in evaluating memory-enhancing agents. Among these, the scopolamine-induced cognitive deficit model is widely accepted due to its ability to mimic cholinergic dysfunction observed in dementia.

This study focuses on the evaluation of memory-enhancing potential of test formulations using C57BL/6 mice, employing validated behavioral, biochemical, and histopathological parameters.

Ethical Approval and Animal Details

The experiment was designed and conducted only after obtaining approval from the Institutional Animal Ethics Committee (IAEC), ensuring compliance with ethical guidelines for laboratory animal use.

• Species: Mouse
• Strain: C57BL/6
• Model Used: Scopolamine-induced cognitive deficit
• Purpose: Evaluation of memory enhancer activity

Experimental Design and Grouping

Animals were allocated into multiple experimental groups to evaluate the comparative efficacy of the test formulations against standard treatment:

• Group G1: Vehicle Control (Na-CMC)
• Group G2: Standard Control – Piracetam (85 mg/kg, p.o.)
• Group G3–G8: Test formulations (DDD & CCC) at different dose levels
• Scopolamine Induction: 1 mg/kg, intraperitoneal, administered from Day-14 to Day-19 in Groups G2 to G8

The test formulations were administered orally from Day-1 to Day-19, following a structured study plan.

Behavioral Assessment of Memory

1. Morris Water Maze (MWM) Test

The Morris Water Maze was used to assess spatial learning and memory. Animals underwent:

• Pre-exposure stage: Day-0
• Experimental trials: Day-11, Day-14, Day-17
• Probe trial: Day-19

Key parameters recorded included:

• Escape latency
• Time spent in target quadrant (Q4)
• Cumulative distance and swimming speed

2. Elevated Plus Maze (EPM) Test

The Elevated Plus Maze test evaluated learning and memory retention through:

• Pre-exposure: Day-0
• Experimental stages: Day-12, Day-15, Day-18

Measured parameters included:

• Transfer latency
• Time spent in open and closed arms
• Number of arm entries

Biochemical and Neurochemical Analysis

Following completion of behavioral assessments, animals were sacrificed for detailed analysis:

• Acetylcholinesterase (AChE) activity in hippocampus
• Antioxidant markers: Superoxide dismutase (SOD) and Catalase in brain hemisphere
• Neurotransmitter estimation by HPLC:
• Acetylcholine
• Dopamine
• Norepinephrine
• Glutamine

Histopathology and Molecular Analysis

Brain and hippocampal tissues were collected for:

• Gross necropsy and histopathological examination
• Western blot analysis for molecular evaluation of neuroprotective markers

These analyses provided structural and molecular evidence supporting behavioral findings.

Study Endpoints

Primary endpoints included:

• Body weight, feed, and water consumption
• Behavioral performance in MWM and EPM tests
• Biochemical and neurotransmitter levels
• Histopathological observations

The scopolamine-induced cognitive deficit model in C57BL/6 mice proved to be a robust and reliable method for assessing memory-enhancing potential of test formulations. Integration of behavioral, biochemical, neurochemical, and histopathological parameters allows comprehensive evaluation of neuroprotective and nootropic effects.

Such preclinical studies are essential for advancing potential memory-enhancing therapies toward clinical research.

                                                    END OF THE CHAPTER

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