L-β-N-oxalyl-α,β-diaminopropionic acid toxicity in motor neurons.

The excitatory amino acid L-β-N-oxalyl-α,β-diaminopropionic acid (L-β-ODAP) in Lathyrus sativus L. is proposed as the causative agent of the neurodegenerative disease neurolathyrism. We investigated the effect of L-β-ODAP on [Ca2+]i handling, redox homeostasis, and cell death in rat spinal motor neurons.

Studies on neurolathyrism in Ethiopia: dietary habits, perception of risks and prevention.

This study describes the correlation of traditional perceptions and dietary habits with the incidence of neurolathyrism to propose preventive measures. Therefore, 118 households of South Wollo and North Gondar (Amhara Regional State, Ethiopia), of which one third had at least one neurolathyrism affected member, were interviewed. Most of the affected families in this study had one neurolathyrism victim, being predominantly male and of younger age.

Unraveling the mechanism of β-N-oxalyl-α,β-diaminopropionic acid (β-ODAP) induced excitotoxicity and oxidative stress, relevance for neurolathyrism prevention.

β-N-Oxalyl-α,β-diaminopropionic acid (β-ODAP) is a plant metabolite present in Lathyrus sativus (L. Sativus) seeds that is proposed to be responsible for the neurodegenerative disease neurolathyrism. This excitatory amino acid binds to α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and several lines of evidence indicate that β-ODAP triggers motor neuron degeneration by inducing excitotoxic cell death and increasing oxidative stress.

L-beta-ODAP alters mitochondrial Ca2+ handling as an early event in excitotoxicity.

The neurotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-beta-ODAP) is an L-glutamate analogue at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptors in neurons and therefore acts as an excitotoxic substance. Chronic exposure to L-beta-ODAP present in Lathyrus sativus L. (L.

Ca(2+) regulation of connexin 43 hemichannels in C6 glioma and glial cells.

Connexin hemichannels have a low open probability under normal conditions but open in response to various stimuli, forming a release pathway for small paracrine messengers. We investigated hemichannel-mediated ATP responses triggered by changes of intracellular Ca(2+) ([Ca(2+)](i)) in Cx43 expressing glioma cells and primary glial cells. The involvement of hemichannels was confirmed with gja1 gene-silencing and exclusion of other release mechanisms.

Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model.

Gap junctions (GJs) have been demonstrated to communicate cell death signals from apoptotic to healthy cells, thereby spatially extending apoptosis. Before being incorporated into GJs, hemichannels (hemi-GJs) are normally closed but recent evidence suggests that they can be opened by various messengers and conditions, thereby forming a pore through which molecules can enter or leave the cell potentially leading to cell death. The aim of this study was to determine the contribution of GJs and hemichannels in the communication of apoptosis toward surrounding cells.

In situ bipolar electroporation for localized cell loading with reporter dyes and investigating gap junctional coupling.

Electroporation is generally used to transfect cells in suspension, but the technique can also be applied to load a defined zone of adherent cells with substances that normally do not permeate the plasma membrane. In this case a pulsed high-frequency oscillating electric field is applied over a small two-wire electrode positioned close to the cells. We compared unipolar with bipolar electroporation pulse protocols and found that the latter were ideally suited to efficiently load a narrow longitudinal strip of cells in monolayer cultures.

Neurobarrier coupling in the brain: adjusting glucose entry with demand.

Glucose transport over the blood-brain barrier (BBB) is a nonrate-limiting step and has therefore received little attention as a possible adjustment point within the transport reaction cascade from blood glucose to brain cell glycolysis. Considerations of the normal working point of facilitated BBB glucose shuttling via the GLUT-1 protein indicate that the transport is working at about one-third of T(max) under basal conditions. Substitution of T(max) estimates indicates that the transport is then just enough to keep up with glucose consumption, maintaining the steady state.