Hyperhomocysteinemia (HHcy) in mammals can produce neurological deficits, such as memory loss. The cause of the neurological issues is assumed to be due to homocysteine (HCY) binding to glutamatergic receptors in the central nervous system (CNS). High levels of HCY in the CNS are also associated with Amyotrophic Lateral Sclerosis (ALS) and Parkinson’s disease. Thus, understanding the detailed mechanisms of HCY in model preparations could be useful in developing potential treatments to neurodegenerative diseases with overlapping symptoms to HHcy. The aim of this study is to investigate the efficacy of HCY as an agonist at glutamatergic synapses in invertebrates. The glutamatergic synapses of the larval Drosophila melanogaster (D. melanogaster) and Procambarus clarkii (P. clarkii) neuromuscular junctions (NMJs) were utilized to examine the effects of applying HCY. Measurements of evoked synaptic transmission in both preparations revealed that 100 mM of HCY did not have any consistent effect. The expectation was that the acute action of HCY would have activated the glutamate receptors and then desensitized them so evoked transmission would be blocked. The pharmacological receptor profile of these NMJ receptors are of a quisqualate subtype and not a kainate, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate receptor (NMDA) subtype. Consequently, HCY may not have any action on quisqualate glutamate receptor subtypes. The findings of this experiments could provide clinical implications regarding relevant pharmacological treatments in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease.
Funded by student laboratory fees Dept. of Biology, Univ. of KY. The course is neurophysiology lab (Bio446, Bio650) and personal funds (RLC).
Grau, Elizabeth; Stanback, Alexandra E.; Bradley, Alec; Cantrell, Danielle; Eversole, Samantha; Grachen, Carolyn; Hall, Kaylee; Hawthorne, Danielle; Kinmon, Claire; Ortiz Guerrero, Paula; Patel, Bhavik; Samuels, Kaitlyn; Suryadevara, Chinni; Valdes, Gia; Wycoff, Samuel; and Cooper, Robin L., "Investigating the Effects of Homocysteine as an Agonist on Invertebrate Glutamatergic Synapses" (2018). Biology Faculty Publications. 146.