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.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Ryan DP,Henzel KS,Pearson BL,Siwek ME,Papazoglou A,Guo L,Paesler K,Yu M,Müller R,Xie K,Schröder S,Becker L,Garrett L,Hölter SM,Neff F,Rácz I,Rathkolb B,Rozman J,Ehninger G,Klingenspor M,Klopstock T,Wolf E,Wursdoi
10.1038/mp.2017.53subject
Has Abstractpub_date
2018-05-01 00:00:00pages
1345-1355issue
5eissn
1359-4184issn
1476-5578pii
mp201753journal_volume
23pub_type
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