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Nrf2 Deficiency Attenuates Synaptic Plasticity in Mice, Mimicking the Aging Phenotype
Author(s) -
ValcarcelAres Marta Noa,
Tucsek Zsuzsanna,
Tarantini Stefano,
Hertelendy Peter,
Gautam Tripti,
Sonntag William E,
Deak Ferenc,
Ungvari Zoltan,
Csiszar Anna
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.951.2
Subject(s) - long term potentiation , neuroscience , schaffer collateral , synaptic plasticity , hippocampal formation , excitatory postsynaptic potential , hippocampus , barnes maze , environmental enrichment , neuroplasticity , morris water navigation task , psychology , stimulation , biology , inhibitory postsynaptic potential , medicine , spatial learning , receptor
There is increasing evidence that Nrf2/ARE signaling regulates lifespan and/or health span both in model organisms and laboratory rodents. Aging is associated with progressive Nrf2 dysfunction, impairing cellular resilience and promoting oxidative stress and inflammation. Age‐dependent impairment in the induction of hippocampal long‐term potentiation (LTP) is well documented, providing a likely neural basis for age‐related decline in learning and memory. While previous studies showed that Nrf2 dysfunction promotes neuronal death and administration of Nrf2 activators improve learning and memory in aged rodents, the effects of age‐related Nrf2 dysfunction on synaptic function are not well understood. To determine the effect of Nrf2 deficiency on cognition and synaptic plasticity, we compared performance of Nrf2 −/− and control mice on various behavioral tests including the elevated plus maze, the radial arm water maze (RAWM) and novel object recognition test. To determine whether Nrf2 deficiency compromises neuronal mechanisms of learning and memory, extracellular recordings were performed from acute hippocampal slices using multi‐electrode arrays. Field excitatory post‐synaptic potentials were invoked through stimulation of the Schaffer collateral and obtained from the CA1 area. We found that Nrf2 −/− mice have a reduced LTP elicited by high frequency stimulation in hippocampal slices. Reduced LTP in Nrf2 −/− mice was associated with a compromised performance in the elevated plus maze learning test and the novel object recognition test. Together, these results provide additional evidence that intact Nrf2 signaling importantly contributes to brain health, preserving hippocampal synaptic plasticity and cognitive function. Further studies are needed to elucidate the neuronal mechanisms impacted by Nrf2 deficiency, determining the potential roles of oxidative stress and inflammatory processes. Support or Funding Information This work was supported by grants from the American Heart Association and the National Institute on Aging