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Ryan, D.P.* ; Henzel, K.S.* ; Pearson, B.L.* ; Siwek, M.E.* ; Papazoglou, A.* ; Guo, L.* ; Paesler, K.* ; Yu, M.* ; Müller, R.* ; Xie, K.* ; Schröder, S.* ; Becker, L. ; Garrett, L. ; Hölter, S.M. ; Neff, F. ; Rácz, I. ; Rathkolb, B. ; Rozman, J. ; Ehninger, G.* ; Klingenspor, M.* ; Klopstock, T.* ; Wolf, E.* ; Wurst, W. ; Zimmer, A.D.* ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Sidiropoulou, K.* ; Weiergräber, M.* ; Zhou, Y.* ; Ehninger, D.*

A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

Mol. Psychiatry 23, 1345-1355 (2017)
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Licenced for HMGU: Publ. Version/Full Text online available 05/2022
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.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.53.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Quellenangaben Volume: 23, Issue: 5, Pages: 1345-1355 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed