Ryan, D. P., Henzel, K. S., Pearson, B. L., Siwek, M. E., Papazoglou, A., Guo, L., Paesler, K., Yu, M., Mueller, R., Xie, K., Schroeder, S., Becker, L., Garrett, L., Hoelter, S. M., Neff, F., Racz, I. ORCID: 0000-0002-1549-3616, Rathkolb, B., Rozman, J., Ehninger, G., Klingenspor, M., Klopstock, T., Wolf, E., Wurst, W., Zimmer, A., Fuchs, H., Gailus-Durner, V., de Angelis, M. Hrabe, Sidiropoulou, K., Weiergraeber, M., Zhou, Y. and Ehninger, D. (2018). A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice. Mol. Psychiatr., 23 (5). S. 1345 - 1356. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5578

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Abstract

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ryan, D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henzel, K. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearson, B. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siwek, M. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papazoglou, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guo, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paesler, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xie, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garrett, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelter, S. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neff, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Racz, I.UNSPECIFIEDorcid.org/0000-0002-1549-3616UNSPECIFIED
Rathkolb, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rozman, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehninger, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klingenspor, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klopstock, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wurst, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmer, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gailus-Durner, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Angelis, M. HrabeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sidiropoulou, K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiergraeber, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehninger, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-187087
DOI: 10.1038/mp.2017.53
Journal or Publication Title: Mol. Psychiatr.
Volume: 23
Number: 5
Page Range: S. 1345 - 1356
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5578
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FOLIC-ACID; S-ADENOSYLMETHIONINE; DNA METHYLATION; GENE-EXPRESSION; VITAMIN-B-12 CONCENTRATIONS; HISTONE DEACETYLASE; POTASSIUM CHANNEL; UNITED-STATES; TUBE DEFECTS; METHIONINEMultiple languages
Biochemistry & Molecular Biology; Neurosciences; PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18708

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