, Volume 179, Issue 4, pp 621-630
Date: 15 Dec 2006

Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25–35) are dependent on stimulation-protocol and genetic background

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Abstract

The aggregation of beta-amyloid to plaques in the brain is one of the hallmarks of Alzheimer disease (AD). Numerous studies have tried to elucidate to what degree amyloid peptides play a role in the neurodegenerative developments seen in AD. While most studies report an effect of amyloid on neural activity and cognitive abilities of rodents, there have been many inconsistencies in the results. This study investigated to what degree the different genetic backgrounds affect the outcome of beta-amyloid fragment (25–35) on synaptic plasticity in vivo in the rat hippocampus. Two strains, Wistar and Lister hooded rats, were tested. In addition, the effects of a strong (600 stimuli) and a weak stimulation protocol (100 stimuli) on impairments of LTP were analysed. Furthermore, since the state of amyloid aggregation appears to play a role in the induction of toxic processes, it was tested by dual polarisation interferometry to what degree and at what speed beta-amyloid (25–35) can aggregate in vitro. It was found that 100 nmol beta-amyloid (25–35) injected icv did impair LTP in Wistar rats when using the weak but not the strong stimulation protocol (P < 0.001). One-hundred nano mole of the reverse sequence amyloid (35–25) had no effect. LTP in Lister Hooded rats was not impaired by amyloid at any stimulation protocol. The aggregation studies showed that amyloid (25–35) aggregated within hours, while amyloid (35–25) did not. These results show that the genetic background and the stimulation protocol are important variables that greatly influence the experimental outcome. The fact that amyloid (25–35) aggregated quickly and showed neurophysiological effects, while amyloid (35–25) did not aggregate and did not show any effects indicates that the state of aggregation plays an important role in the physiological effects.