Study of the etiology of neurolathyrism, a human neurodegenerative disease with nutritional causes
type: CreativeWork
description: Prolonged exclusive consumption of grass pea (Lathyrus sativus L.) seeds under certain conditions initiates the development of neurolathyrism, a disease characterized by neurodegeneration, which results in a spastic paraparesis. The neuro-excitatory amino acid β-N-oxalyl-L-α,β-diaminopropionic acid (L-β-ODAP) present in grass pea was proposed as the cause of the disease. Although the mechanism of its action has not been conclusively elucidated, excitotoxicity and oxidative stressrelated dysfunctions have been proposed to explain at least part of its neurotoxicity. The deficiency of grass pea in the sulphur-containing amino acids methionine (Met) and cysteine (Cys) may contribute to the L-β-ODAP-induced increase in oxidative stress. In this research project, the effect of L-β-ODAP was studied as compared to L-glutamate on the permeability of the blood-brain barrier (BBB), on the survival and functioning of neuronal and glial cells, and free amino acids were analyzed in urine of neurolathyrism patients. An in vitro model for the BBB, consisting of brain capillary endothelial cells (BCEC) co-cultured with glial cells, was exposed to L-β-ODAP or the excitatory amino acid L-glutamate. Acute exposure to either L-β-ODAP or L-glutamate had no effect on the BBB permeability, whereas chronic exposure to L-β-ODAP (but not to L-glutamate) increased its permeability. Since no information is available about L-β-ODAP transport across the BBB, this increased permeability may indicate a possible entry point of L-β-ODAP into the central nervous system (CNS). Once L-β-ODAP entered the CNS, neurotoxicity can be initiated. Although neurolathyrism research has largely focused on the direct neurotoxic effects of L-β-ODAP, non-neuronal cells such as glial cells may also be involved in this process. Therefore, gliotoxicity of L-β-ODAP was studied in C6 glioma cells and primary glial cells. Cell death was evaluated by propidium iodide (PI) staining, whereas cell survival was quantified by th…
abstract: Prolonged exclusive consumption of grass pea (Lathyrus sativus L.) seeds under certain conditions initiates the development of neurolathyrism, a disease characterized by neurodegeneration, which results in a spastic paraparesis. The neuro-excitatory amino acid β-N-oxalyl-L-α,β-diaminopropionic acid (L-β-ODAP) present in grass pea was proposed as the cause of the disease. Although the mechanism of its action has not been conclusively elucidated, excitotoxicity and oxidative stressrelated dysfunctions have been proposed to explain at least part of its neurotoxicity. The deficiency of grass pea in the sulphur-containing amino acids methionine (Met) and cysteine (Cys) may contribute to the L-β-ODAP-induced increase in oxidative stress. In this research project, the effect of L-β-ODAP was studied as compared to L-glutamate on the permeability of the blood-brain barrier (BBB), on the survival and functioning of neuronal and glial cells, and free amino acids were analyzed in urine of neurolathyrism patients. An in vitro model for the BBB, consisting of brain capillary endothelial cells (BCEC) co-cultured with glial cells, was exposed to L-β-ODAP or the excitatory amino acid L-glutamate. Acute exposure to either L-β-ODAP or L-glutamate had no effect on the BBB permeability, whereas chronic exposure to L-β-ODAP (but not to L-glutamate) increased its permeability. Since no information is available about L-β-ODAP transport across the BBB, this increased permeability may indicate a possible entry point of L-β-ODAP into the central nervous system (CNS). Once L-β-ODAP entered the CNS, neurotoxicity can be initiated. Although neurolathyrism research has largely focused on the direct neurotoxic effects of L-β-ODAP, non-neuronal cells such as glial cells may also be involved in this process. Therefore, gliotoxicity of L-β-ODAP was studied in C6 glioma cells and primary glial cells. Cell death was evaluated by propidium iodide (PI) staining, whereas cell survival was quantified by th…
author: Van Moorhem, Marijke
language: eng
keywords: Medicine and Health Sciences
date published: 2011
date modified: 2026-07-24T02:23:00Z
provider: Ghent University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Ghent University. Faculty of Medicine and Health Sciences

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1854/LU-4096675