Hormetic effect of amyloid-beta peptide in hippocampal synaptic plasticity and memory


  • Daniela Puzzo University of Catania
  • Agostino Palmeri University of Catania


hormesis, peptide, hippocampal


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 (Aï¢), a peptide widely known because it is produced in high amounts during Alzheimer’s disease (AD). Aï¢ 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 Aï¢42 enhance synaptic plasticity and memory (Puzzo et al, J Neurosci, 2008) and that endogenous Aï¢ 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 Aï¢ 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 Aï¢ (from 2 pM to 20 μM). Results: We demonstrated that Aï¢ has a hormetic effect (Puzzo et al, Neurobiol Aging, 2012) with low-doses (200 pM) stimulating synaptic plasticity and memory and high-doses (≥ 200 nM) inhibiting these processes. Conclusions: Our results suggest that, paradoxically, very low doses of Aï¢ might serve to enhance memory at appropriate concentrations and conditions. These findings raise several issues when designing effective and safe approaches to AD therapy.