%0 Journal Article
%T Hormetic effect of amyloid-beta peptide in hippocampal synaptic plasticity and memory
%A Daniela Puzzo
%A Agostino Palmeri
%J International Journal of High Dilution Research
%D 2012
%I Universidade Estadual Paulista
%X Background: The term hormesis refers to a biphasic dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition represented by a J-shaped or U-shaped curve, depending on the parameter measured (Calabrese and Baldwin, Hum Exp Toxicol, 2002). Indeed, several, if not all, physiological molecules (i.e. glutamate, glucocorticoids, nitric oxide) are likely to present a hormetic effect, exhibiting opposite effects at high or low concentrations. In the last few years, we have focused on amyloid-beta (A ¡¥   ¡é), a peptide widely known because it is produced in high amounts during Alzheimer ¡éa  a ¡és disease (AD). A ¡¥   ¡é is considered a toxic fragment causing synaptic dysfunction and memory impairment (Selkoe, Science, 2002). However, the peptide is normally produced in the healthy brain and growing evidences indicate that it might have a physiologic function. Aim: Based on previous results showing that picomolar concentrations of A ¡¥   ¡é42 enhance synaptic plasticity and memory (Puzzo et al, J Neurosci, 2008) and that endogenous A ¡¥   ¡é is necessary for synaptic plasticity and memory (Puzzo et al, Ann Neurol, 2011), the aim of our study was to demonstrate the hormetic role of A ¡¥   ¡é in synaptic plasticity and memory. Methods: We used 3-month old wild type mice to analyze how synaptic plasticity, measured on hippocampal slices in vitro, and spatial reference memory were modified by treatment with different doses of A ¡¥   ¡é (from 2 pM to 20     M). Results: We demonstrated that A ¡¥   ¡é has a hormetic effect (Puzzo et al, Neurobiol Aging, 2012) with low-doses (200 pM) stimulating synaptic plasticity and memory and high-doses ( ¡éa?¡ã £¤ 200 nM) inhibiting these processes. Conclusions: Our results suggest that, paradoxically, very low doses of A ¡¥   ¡é might serve to enhance memory at appropriate concentrations and conditions. These findings raise several issues when designing effective and safe approaches to AD therapy.
%K hormesis
%K peptide
%K hippocampal
%U http://www.feg.unesp.br/~ojs/index.php/ijhdr/article/view/604