Title : Exploring the relationship of locomotor function and olfactory memory as a measure of neurodegeneration in TPI deficient (M80T mutation) drosophila melanogaster larvae, with both regular and high fat diets
Abstract:
M80T mutation of triose phosphate isomerase (TPI) presents one potential contributory pathway for developing Alzheimer’s disease (AD). M80T effects the triose phosphate isomerase (TPI) enzyme activity within the glycolysis pathways producing enhanced levels of methylglyoxal, a neurotoxic substance responsible for protein glycation. Dysregulation of the gut brain axis provides a further potential pathway aggravating AD, with high fat diet (HFD) causing neuroinflammation, contributing to AD.
Objectives:
Drosophila Melanogaster (DM) larvae were used, testing if M80T and HFD influence developing AD. Mutated larvae were tested against w1118 wildtypes as a control, in normal diet (ND) and HFD. Objectives included comparing DM wildtype larvae to TPI mutant expressing larvae, for risk of neurodegeneration, and comparing ND to HFD.
Methods:
Locomotor assays assessed locomotion, tracking 10-minute periods of DM larvae crawling. Learning and memory assays assessed olfactory memory by training procedures of associating odour, N-amyl acetate (AM) or distilled water, with reward. Memory retrieval procedures followed measuring preference to AM.
Results:
Crawling: 90 values, significance between HFD wildtype vs M80T (P = 0.0223), HFD wildtypes and mutations (P < 0.0001), HFD mutations (P = 0.0003) and ND vs HFD of wildtype and M80T (P = 0.0239).
Learning and memory: 76 values, significance between ND wildtype vs M80T AM reward (P = 0.00018), HFD wildtype vs M80T AM reward (P = 0.0425), wildtype distilled water reward ND vs HFD (P = 0.0095), ND M80T vs wildtypes (P < 0.0001), ND vs HFD wildtypes (P = 0.0001), ND mutations (P = 0.0016) and HFD mutations (P = 0.0090).
Conclusions:
M80T larvae crawled faster than W1118, unexpectedly as neurodegeneration predicts slower locomotion. Learning and memory assays showed impaired memory in M80T larvae relative to W1118, supporting the hypothesis that TPI mutations cause neurodegeneration. Both assays gave positive data on HFD causing neurodegeneration. Therefore, further research is needed of neurodegeneration on locomotor function to assess repeatability.
Audience Take Away
- The effects of both a high fat diet and dysfunction of a glycolytic enzymes (TPI mutation M80T) on developing neurodegeneration
- The use of changing diet in lifestyle as a neuroprotective factor in neurodegenerative diseases in clinical and epidemiological environments
- The use of a locomotor assay as a measure of locomotor function for drosophila melanogaster and how it can be applied to other research conditions
- The potential for more research to be carried out in this area to investigate what it is about a high fat diet that causes the increase in neurodegeneration and begin to work out mechanisms to counteract this
