title: 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.
abstract: 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. non-target quadrants 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.
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada ; Faculty of Health Sciences, Department of Pharmacology and Therapeutics, College of Medicine, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Snow
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada ; Faculty of Health Sciences, Department of Pharmacology and Therapeutics, College of Medicine, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Payam S
authors.initials: PS
authors.lastname: Pahlavan
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada ; Faculty of Health Sciences, Department of Pharmacology and Therapeutics, College of Medicine, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: McAllister
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Platt
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Shoug
authors.initials: S
authors.lastname: Alashmali
authors.affiliation: Department of Psychological and Social Sciences, Pennsylvania State University Abington Abington, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bernstein
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Miyoung
authors.initials: M
authors.lastname: Suh
authors.affiliation: Division of Neurodegenerative Disorders, St. Boniface Hospital Research Winnipeg, MB, Canada ; Faculty of Health Sciences, Department of Pharmacology and Therapeutics, College of Medicine, University of Manitoba Winnipeg, MB, Canada ; Faculty of Engineering, Department of Electrical and Computer Engineering, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Benedict C
authors.initials: BC
authors.lastname: Albensi
keywords: Morris water maze; activity-dependent plasticity; cAMP-response element binding protein; early growth response-2; nuclear factor (erythroid-derived 2)-like 2; nuclear factor kappa B; spatial memory; transcription factors