Journal Article

DZNE-2020-06257

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

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

2018
Macmillan London

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Please use a persistent id in citations: doi:10.1038/mp.2017.53

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.

Keyword(s): Animals (MeSH) ; Cognition: physiology (MeSH) ; DNA Methylation (MeSH) ; Diet (MeSH) ; Dietary Supplements: adverse effects (MeSH) ; Epigenesis, Genetic (MeSH) ; Fathers (MeSH) ; Folic Acid: metabolism (MeSH) ; Hippocampus: metabolism (MeSH) ; Large-Conductance Calcium-Activated Potassium Channel beta Subunits (MeSH) ; Learning: drug effects (MeSH) ; Male (MeSH) ; Memory: drug effects (MeSH) ; Methionine: metabolism (MeSH) ; Methionine Adenosyltransferase (MeSH) ; Methylation (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Neurons: physiology (MeSH) ; Paternal Inheritance: genetics (MeSH) ; Paternal Inheritance: physiology (MeSH) ; Promoter Regions, Genetic (MeSH) ; Kcnmb2 protein, mouse ; Large-Conductance Calcium-Activated Potassium Channel beta Subunits ; Folic Acid ; Methionine ; Methionine Adenosyltransferase

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Contributing Institute(s):

1. Molecular and Cellular Cognition (AG Ehninger)
2. Animal Facility Bonn (Animal Facility Bonn)
3. Clinical Dementia Research München (Clinical Dementia Research München)
4. Genome Engineering (AG Wurst)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

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