A Locomotor Activity Study of the Effects of L‐Serine to Neurodegeneration Impacts of Beta‐Methylamino‐L‐alanine in Drosophila melanogaster

Abstract

Amyotrophic Lateral Sclerosis‐Parkinsonism Dementia Complex (ALS‐PDC) is a neurodegenerative disease that described by loss of motor function, tremors, and dementia due to neurodegeneration. The disease is thought to be caused by Beta‐Methylamino‐L‐Alanine (BMAA), a neurotoxin from blue‐green algae. Since it has a structure that is similar to glutamate, BMAA act as an agonist to the glutamate receptor N‐methyl‐D‐aspartate which lead to excitotoxicity and degenerate neurons. L‐serine is an essential amino acid that has shown to interfere with the effect of BMAA in vivo studies. The purpose of this research is to further test the novel impact of L‐serine to BMAA‐induced fly in long‐term study. The interaction of BMAA and L‐serine was analyzed through circadian rhythm activity and viability of wild‐type Drosophila melanogaster in ALS‐PDC model. We used two Drosophila Activity Monitor (DAM) systems to measure activity of 64 fruit flies (Gender and Age‐Match). The experimental groups were fed with L‐serine, BMAA, BMAA+L‐serine and the control group was fed with standard fly agar. Fly activity was recorded by the number of fly pass the IR beam in the monitor for 10‐day (12L/12D at 22°C). After 10 days, circadian rhythm data showed BMAA flies increased activity over the first few days, and decreased gradually to the end of the period. BMAA‐induced flies (n = 12) does not show pattern of regular activity in L/D as compared to Control (n = 15) and L‐serine (n = 16). The co‐fed BMAA+L‐serine (n = 7) showed a similar pattern as the Control. For daytime vs nighttime activity (mean ± s.e.m), Control (n = 15) shown regular activity (day: 137 ± 13%, night: 21 ± 5%) as compared to BMAA (n = 12) that shown high activity in dark cycle (day: 162 ± 10%, night: 155 ± 21%). Moreover, the cofed L‐serine + BMAA (n = 7) exhibited normal daytime activity but not nighttime activity (day: 138 ± 14%, night: 167 ± 31%). The data from DAM shows the abnormal activity of flies in long term when inducing with BMAA such as abrupt sleep due to high activity during dark phase. L‐serine shows to reduce down the high activity when cofed with BMAA. This supports our hypothesis of L‐serine ameliorates the effects of BMAA in fly. This preliminary data is a starting point for further research in drug discovery for ALS‐PDC.Support or Funding InformationAcknowledgementsThis work was funded by the Fresno State Undergraduate Research Grant Award (2019–2020), and Howard P. Kubo, M.D. Award for Outstanding Achievement in Biomedical Science.