ALS-IgG affects multiple modes of synaptic transmission

PAGANI M.R., REISIN C.R., UCHITEL O.D.

Cordoba, Argentina

Taller; Taller de Neurociencias; 2005

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. There is evidence supporting the involvement of autoimmune mechanisms in ALS. Different authors have shown that structural alterations in rodent motoneurons are mediated by IgG purified from ALS patients (ALS-IgG). However, the underlying mechanisms have not been investigated and, as a result, it is not clear what the significance of antibodies in ALS is and how it could lead to neuronal death. Has been well documented that acute application of ALS-IgG affects spontaneous synaptic transmission, but there is only one report showing that ALS-IgG affects evoked neurotransmitter release at a low frequency of stimulation. Moreover, there is no information about the effects of ALS-IgG on synaptic activity at physiological frequencies of stimulation and on short-term synaptic plasticity. Thus, we investigated whether ALS-IgG or IgG from control patients affect electrical nerve stimulation-evoked end-plate potentials at different physiological frequencies of stimulation (1, 20, 40 and 100 Hz). Furthermore, we studied the effects of ALS-IgG on short-term synaptic plasticity by paired pulse facilitation and post-tetanic potentiation. Our present findings have shown that ALS-IgG immunoreactive against neuromuscular synapses did not affect short-term synaptic plasticity, but enhanced synchronous and asynchronous synaptic transmission in an activity-depended way. All together these results have shown that ALS-IgG induce a deep change in neuromuscular synaptic transmission, which may promote those structural alterations observed in motoneurons.