PRELIMINARY ANALYSIS OF β-METHYLAMINO-L-ALANINE INTERACTIONS WITH CU/ZN SUPEROXIDE DISMUTASE IN AMYOTROPHIC LATERAL SCLEROSIS ZEBRAFISH MODELS
Author: Elizabeth Pflugradt
Major: Molecular and Cellular Biology
Graduation Year: 2016
Thesis Advisor: Roger Sher
Description of Publication: Amyotrophic Lateral Sclerosis (ALS) is a terminal neurodegenerative disease with symptoms including limb-onset muscle wasting, difficulties swallowing and breathing, leading to death. Sporadic ALS occurs in 90% of patients, while 10% of cases are familial (FALS). Twenty percent of FALS cases are a result of mutation in the copper-zinc superoxide dismutase (SOD1) gene, leading to the activation of the mitochondrial apoptosis pathway. Meanwhile, a prominent cause of sporadic ALS is exposure to neurotoxins, such as β-methylamino-L-alanine (BMAA). BMAA has been suggested to induce selective motor neuron death, which is observed in ALS patients. While research has been done to how BMAA may impacts organisms on the cellular level, not much has been performed on the genetic or epigenetic level. This research investigates how BMAA and mutations in the SOD1 gene affect the regulation of well-known neurological genes. Within the year, zebrafish from four different genotypes were subjected to three different BMAA concentrations, and spinal samples from these fish were collected. RNA was extracted from these and cDNA was produced from the resulting RNA. RNA concentrations varied significantly in concentration and purity, while cDNA concentrations were more pure and higher in concentration. The spinal samples also displayed that fish exposed to 2.5 μg/L of BMAA had the lowest levels of actin transcripts, reflected in previous work that these fish would have the shortest motor neuron axons. These samples can now be used to perform transcriptome analysis to detect the regulation of neurological genes depending on BMAA concentration and SOD1 mutation.
Location of Publication:
URL to Thesis: https://digitalcommons.library.umaine.edu/honors/410