Effects on Learning/Memory of a Mutation in Da7: A Fruit Fly Homolog of the Alzheimer's Related Gene for the nAChR a7

Overview

Objectives/Goals The purpose of this project is to test the effects on learning/memory and locomotion of a mutation of the gene D-Alpha 7 (Da7) (specifically the P-Delta-EY6 allele - PDEY6), a Drosophila melanogaster (fruit fly) homolog of the Alzheimer's Disease (AD) related human gene that encodes the Nicotinic Acetylcholine Receptor Alpha 7 (nAChR a7). My hypothesis was that the mutants expressing the Da7 PDEY6, which impedes the production of the fruit fly equivalent of the nAChR a7, will show a significant decline in learning/memory retention and locomotion, similar to the Amyloid-Beta Arc-42 (AB-42) mutants (AD model), when compared to flies that express the corresponding wild type (WT) receptor. Methods/Materials Drosophila stocks and care: Da7 PDEY6 as test subject, AB-42 as positive control, WT flies as negative control, Instant Drosophila Media, Appropriate Vials/Caps, Dissecting Microscope. For Olfactory Shock Learning: T-maze (self-built), Training Chamber (self-built), Shock - 60 volts/3.75 seconds, Odors - 3- Octanol and 4-Methylcyclohexanol (MCH). Results 1. Climbing Assay Success Rates: PDEY6 -- 61.2%, AB-42 -- 60.2%, WT -- 79.5% 2. Short Term Memory Success Rates: PDEY6 -- 49%, AB-42 -- 46%, WT -- 81% 3. Long Term Memory Success Rates: PDEY6 -- 41.5%, AB-42 -- 39%, WT -- 78% 4. P-value for AB-42, PDEY6 consistently >90% 5. P-value for WT & AB-42/PDEY6 consistently less than 10^-6 Conclusions/Discussion 1. Hypothesis proven: PDEY6 (and AB-42) populations show ~40% decline in short/long term memory, ~23% deterioration in locomotion relative to the WT populations. 2. For both short and long term memory tests: The differences between the 3-week and 4-week flies not statistically significant; Additionally, no performance impact by odor 3. Additional "loss" of long term memory compared to short term for 15% of mutants, 5% of WT flies 4. Higher impact of lack of Da7 on memory/learning than climbing, which is expected 5. For AB-42 & PDEY6: Null hypothesis rejected - Strong relationship between mutants exists 6. For WT/AB-42 & WT/PDEY6: Null hypothesis accepted - Relationship between WT and mutants non-existent 7. These conclusions provide further motivation to study nAChR a7 and its potential for AD research.

Awards (1)

• First Place

Competition history

• CSEF 2018 Zoology · Entry S2311

Resources

• CSEF project summary ↗

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