Frontiers in Molecular Neuroscience (Nov 2015)

Morris water maze training in mice elevates hippocampal levels of transcription factors nuclear factor (erythroid-derived 2)-like 2 and nuclear factor kappa B p65

  • Wanda eSnow,
  • Wanda eSnow,
  • Payam ePahlavan,
  • Payam ePahlavan,
  • Jelena eDjordjevic,
  • Danielle eMcAllister,
  • Eric ePlatt,
  • Shoug eAlashmali,
  • Michael J Bernstein,
  • Miyoung eSuh,
  • Benedict C Albensi,
  • Benedict C Albensi,
  • Benedict C Albensi

DOI
https://doi.org/10.3389/fnmol.2015.00070
Journal volume & issue
Vol. 8

Abstract

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Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs a non-target quadrant of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory.

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