Different electrophysiological actions of 24-and 72-hour aggregated amyloid-beta oligomers on hippocampal field population spike in both anesthetized and awake rats

作者：Orban Gergely; Voelgyi Katalin; Juhasz Gabor; Penke Botond; Kekesi Katalin Adrienna; Kardos Jozsef; Czurko Andras^*

来源：Brain Research, 2010, 1354: 227-235.

DOI：10.1016/j.brainres.2010.07.061

• Alzheimer's disease
• Amyloid
• Excitability
• Oligomer
• Atomic force microscopy

Diffusible oligomeric assemblies of the amyloid vs-protein (A beta) could be the primary factor in the pathogenic pathway leading to Alzheimer's disease (AD). Converging lines of evidence support the notion that AD begins with subtle alterations in synaptic efficacy, prior to the occurrence of extensive neuronal degeneration. Recently, however, a shared or overlapping pathogenesis for AD and epileptic seizures occurred as aberrant neuronal hyperexcitability, as well as nonconvulsive seizure activity were found in several different APP transgenic mouse lines. This generated a renewed attention to the well-known comorbidity of AD and epilepsy and interest in how A beta oligomers influence neuronal excitability. In this study therefore, we investigated the effect of various in vitro-aged A beta(1-42) oligomer solutions on the perforant pathway-evoked field potentials in the ventral hippocampal dentate gyrus in vivo. Firstly, A beta oligomer solutions (1 mu l, 200 mu M) which had been aggregated in vitro for 0, 24 or 72 h were injected into the hippocampus of urethane-anesthetized rats, in parallel with in vitro physico-chemical characterization of A beta oligomerization (atomic force microscopy, thioflavin-T fluorescence). We found a marked increase of hippocampal population spike (pSpike) after injection of the 24-h A beta oligomer solution and a decrease of the pSpike amplitude after injection of the 72-h A beta oligomer. Since urethane anesthesia affects the properties of hippocampal evoked potentials, we repeated the injection of these two A beta oligomer solutions in awake, freely moving animals. Evoked responses to perforant pathway stimulation revealed a 70% increase of pSpike amplitude 50 min after the 24-h A beta oligomer injection and a 55% decrease after the 72-h A beta oligomer injection. Field potentials, that reflect synaptic potentials, were not affected by the A beta injection. These results demonstrate that oligomeric A beta aggregates elicit opposite electrophysiological effects on neuronal excitability which depend on their degree of oligomerization.

• 出版日期2010-10-1
• 单位河北医科大学