TY - JOUR
T1 - Sex-specific effects of chronic creatine supplementation on hippocampal-mediated spatial cognition in the 3xtg mouse model of alzheimer’s disease
AU - Snow, Wanda M.
AU - Cadonic, Chris
AU - Cortes-Perez, Claudia
AU - Adlimoghaddam, Aida
AU - Chowdhury, Subir K.Roy
AU - Thomson, Ella
AU - Anozie, Adama
AU - Bernstein, Michael J.
AU - Gough, Kathleen
AU - Fernyhough, Paul
AU - Suh, Miyoung
AU - Albensi, Benedict C.
N1 - Funding Information:
Funding: This research was funded by St. Boniface Hospital Research Foundation (to BA; Grant numbers 1406–3216, 1403–3131, and 1410–3216), Research Manitoba (to B.A.; Postdoctoral Fellowship to WS), the Alzheimer’s Society of Manitoba (to B.A.), the Canadian Institutes of Health Research (Grant number PJT-162144), and the Honorable Douglas and Patrician Everett, Royal Canadian Properties Limited Endowment Fund (Grant number 1403–3131). B.A. is a Research Affiliate at the University of Manitoba’s Centre on Aging, a core member of the Biomedical Engineering Graduate Program at the University of Manitoba, a scientist at the Children’s Hospital Research Institute of Manitoba, and the Honorable Douglas Everett, Patricia Everett, and the Royal Canadian Properties Endowment Fund Chair. B.A. is also the Manitoba Dementia Research Chair.
Funding Information:
This research was funded by St. Boniface Hospital Research Foundation (to BA; Grant numbers 1406?3216, 1403?3131, and 1410?3216), Research Manitoba (to B.A.; Postdoctoral Fellowship to WS), the Alzheimer?s Society of Manitoba (to B.A.), the Canadian Institutes of Health Research (Grant number PJT-162144), and the Honorable Douglas and Patrician Everett, Royal Canadian Properties Limited Endowment Fund (Grant number 1403?3131). B.A. is a Research Affiliate at the University of Manitoba?s Centre on Aging, a core member of the Biomedical Engineering Graduate Program at the University of Manitoba, a scientist at the Children?s Hospital Research Institute of Manitoba, and the Honorable Douglas Everett, Patricia Everett, and the Royal Canadian Properties Endowment Fund Chair. B.A. is also the Manitoba Dementia Research Chair. Acknowledgments: The authors wish to thank Alana Slike for her technical expertise with Western blotting experiments.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity-and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8–9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid β (Aβ) species, whereas Aβ trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain.
AB - The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity-and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8–9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid β (Aβ) species, whereas Aβ trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain.
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U2 - 10.3390/nu12113589
DO - 10.3390/nu12113589
M3 - Article
C2 - 33238473
AN - SCOPUS:85096452355
SN - 2072-6643
VL - 12
SP - 1
EP - 29
JO - Nutrients
JF - Nutrients
IS - 11
M1 - 3589
ER -