Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB

Wanda M. Snow; Chris Cadonic; Claudia Cortes-Perez; Subir K. Roy Chowdhury; Jelena Djordjevic; Ella Thomson; Michael J. Bernstein; Miyoung Suh; Paul Fernyhough; Benedict C. Albensi

doi:10.1101/lm.046284.117

Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB

¹Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, Manitoba R2H 2A6, Canada
²Department of Psychological and Social Sciences, Pennsylvania State University Abington, Abington, Pennsylvania 19001, USA
³Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada
⁴Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, Manitoba R3E 0T6, Canada

Corresponding authors:wsnow_2001{at}yahoo.ca; balbensi{at}sbrc.ca

Abstract

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform (P < 0.05) and increased the time spent in the target quadrant (P < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.

Footnotes

Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.046284.117.

Received July 6, 2017.
Accepted November 3, 2017.

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