Raised nitrate concentration and low SOD activity in the CSF of sporadic ALS patients.

To determine whether or not the occurrence of sporadic amyotrophic lateral sclerosis (sALS) is associated with both excess nitric oxide (NO) metabolites and decreased protective superoxide dismutase (SOD) activity in the cerebrospinal fluid (CSF), we measured nitrate concentration and SOD activity in the CSF of sALS patients and in age- and gender-matched controls. We found stable NO metabolite levels to be significantly higher and SOD activity lower in the CSF of sALS patients. In addition, SOD showed a negative correlation with motor neuron axonal damage expressed as the amplitude of motor action potentials in upper limbs. Our results provide new evidence in vivo suggesting that NO products and SOD activity play a role in oxidant/ antioxidant imbalance in sporadic ALS.

In vivo and in vitro studies of glycine- and glutamate-evoked acetylcholinesterase release from spinal motor neurones: implications for amyotrophic lateral sclerosis/motor neurone disease pathogenesis.

To investigate the spinal cellular structures and molecular mechanisms involved in acetylcholinesterase (AChE) release evoked by both glycine (GLY) and glutamate (GLU)--responses that might play a role in chronic neurotoxicity--we analysed AChE histochemistry and histology upon systemic administration of aspartate (ASP), and conducted in vitro experiments in synaptosomes and slices prepared from mouse spinal ventral horns. Upon superfusion and incubation exposure of these preparations to GLY- and GLU-receptor agonists, we assayed both tissue content and release of AChE, butyrylcholinesterase and lactic dehydrogenase. Histochemical reduction of motor neurone (MN) AChE, calcium dependency, decreases in intracellular AChE and the ratio amongst molecular forms released, suggest that both synaptosomal GLY-evoked AChE release (GLY-EAR) and GLU-receptor-elicited AChE release (GEAR) have release sites located at MN presynaptic terminals. These responses exhibited remarkable postnatal regulation. GEAR seems to be mediated through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptors after the fourth postnatal week and through both NMDA and non-NMDA receptors at earlier stages. Sustained rises of extracellular AChE might link acute excitotoxic injury with several long-lasting pathways leading to chronic neurotoxicity, since AChE molecular properties include: (1) the ability to block cholinergic mechanisms that protect MN against overactivity; (2) activation of ATP-dependent potassium channels; (3) promotion of neurite and axon outgrowth; and possibly (4) stimulation of brain macrophage migration and activation.