title: Stress impairs synaptic plasticity in triple-transgenic Alzheimer's disease mice: rescue by ryanodine.
abstract: BACKGROUND
  A possible contributing factor to the development of cognitive deficits in Alzheimer's disease (AD) patients involves the exposure to early life stress.
  
  
  OBJECTIVE
  We explored the impact of stress on synaptic plasticity (long-term potentiation, LTP) of 6-month-old triple-transgenic mice (3×Tg-AD).
  
  
  METHODS
  3×Tg-AD and control (NonTg) mice were exposed to three stressors at the age of 2 and 4 months. Excitatory postsynaptic potentials were recorded in the stratum radiatum of the CA1 region of hippocampal slices, in a two-pathway paradigm.
  
  
  RESULTS
  Slices taken from 3×Tg-AD mice exhibited significant deficits in LTP compared with NonTg slices. Early stress led to a further decrease in LTP in these mice, while it did not affect NonTg mice. LTP in 3×Tg-AD and stressed 3×Tg-AD mice was rescued by pre-exposure to 0.2 µM ryanodine. In an attempt to find a molecular correlate for the effects of stress in the 3×Tg-AD mice, we found that stressed mice have an altered ratio of Aβ42/40 both in the cortex and hippocampus.
  
  
  CONCLUSIONS
  Stress experiences in young adults may accelerate the cognitive loss in AD mice, adding another dimension to the plethora of factors that lead to AD.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gayane
authors.initials: G
authors.lastname: Grigoryan
authors.forename: Gloria
authors.initials: G
authors.lastname: Biella
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Menahem
authors.initials: M
authors.lastname: Segal
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000503:physiopathology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D012433:Ryanodine / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology
chemical_list: D012433:Ryanodine