Chronic Infusion of Amyloid-β Peptide and Sustained Attention Altered α7 Nicotinic Receptor Density in the Rat Brain

Abstract

It is already known that progressive degeneration of cholinergic neurons in brain areas such as the hippocampus and the cortex leads to memory deficits, as observed in Alzheimer's disease. This work verified the effects of the infusion of amyloid-β (Aβ) peptide associated to an attentional rehearsal on the density of α7 nicotinic cholinergic receptor (nAChR) in the brain of male Wistar rats. Animals received intracerebroventricular infusion of Aβ or vehicle (control - C) and their attention was stimulated weekly (Stimulated Aβ group: S-Aβ and Stimulated Control group: SC) or not (Non- Stimulated Aβ group: N-SAβ and Non-Stimulated Control group: N-SC), using an active avoidance apparatus. Conditioned avoidance responses (CAR) were registered. Chronic infusion of Aβ caused a 37% reduction in CAR for N-SAβ. In S-Aβ, this reduction was not observed. At the end, brains were extracted and autoradiography for α7 nAChR was conducted using [125I]-α-bungarotoxin. There was an increase in α7 density in hippocampus, cortex and amygdala of SAβ animals, together with the memory preservation. In recent findings from our lab using mice infused with Aβ and the α7 antagonist methyllycaconitine, and stimulated weekly in the same apparatus, it was observed that memory maintenance was abolished. So, the increase in α7 density in brain areas related to memory might be related to a participation of this receptor in the long-lasting change in synaptic plasticity, which is important to improve and maintain memory consolidation.