Alcohol Abuse Promotes Changes in Non-Synaptic Epileptiform Activity with Concomitant Expression Changes in Cotransporters and Glial Cells

Abstract

Non-synaptic mechanisms are being considered the common factor of brain damage in status epilepticus and alcohol intoxication. The present work reports the influence of the chronic use of ethanol on epileptic processes sustained by non-synaptic mechanisms. Adult male Wistar rats administered with ethanol (1, 2 e 3 g/kg/d) during 28 days were compared with Control. Non-synaptic epileptiform activities (NEAs) were induced by means of the zero-calcium and high-potassium model using hippocampal slices. The observed involvement of the dentate gyrus (DG) on the neurodegeneration promoted by ethanol motivated the monitoring of the electrophysiological activity in this region. The DG regions were analyzed for the presence of NKCC1, KCC2, GFAP and CD11b immunoreactivity and cell density. The treated groups showed extracellular potential measured at the granular layer with increased DC shift and population spikes (PS), which was remarkable for the group E1. The latencies to the NEAs onset were more prominent also for the treated groups, being correlated with the neuronal loss. In line with these findings were the predispositions of the treated slices for neuronal edema after NEAs induction, suggesting that restrict inter-cell space counteracts the neuronal loss and subsists the hyper-synchronism. The significant increase of the expressions of NKCC1 and CD11b for the treated groups confirms the existence of conditions favorable to the observed edematous necrosis. The data suggest that the ethanol consumption promotes changes on the non-synaptic mechanisms modulating the NEAs. For the lower ethanol dosage the neurophysiological changes were more effective suggesting to be due to the less intense neurodegenertation.

Neurophysics: Understanding brain activity with modeling complex systems mathematics

“…Interestingly, the neurophysiological changes were more effective in the lower ethanol dosage, suggesting that they are due to the less intense neurodegeneration. 2 In 2015, we verified how non-synaptic epileptiform activity in the hippocampal formation were affected by kainic acid administration and showed that elements involved in non-synaptic events are potential targets for drugs to treat neurological disorders where intrinsic excitability is a problem. 3 We then proposed simple rules for learning, inspired by recent machine learning insights and adapted to a realistic spiking neural network, and showed that the incorporation of non-synaptic interaction mechanisms improves cell assembly convergence.…”