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Mouse dad's diet affects his pups' mental health

Evidence is accumulating, at least in animals, that infant development is affected not only by a mother's diet and lifestyle, but also by a father's diet prior to conception.

For example, if male rodents are fed a fat rich diet, their offspring have a tendency to diabetes. A possible cause for this is diet-induced methylation changes to dad's DNA — changes in tiny chemical tags on a strand of DNA which control a gene.

Diet influences epigenetic patterns in the genome by reprogramming both egg and sperm before fertilization.

High concentrations of methyl donor elements can also affect human moms who drink excessive amounts of energy drinks or take too many folic acid pills as you should not get more than 1,000 micrograms of folic acid a day, unless prescribed by your doctor. Too much folic acid can hide signs you lack vitamin B12, which can cause nerve damage.

Large quantities of methyl tags can be introduced by diet, and change when and if genes function.

Methylation tags (orange), on DNA affects gene, and thus protein, function.
Image credit: Imperial College London

In mice, a father's diet can also affect cognitive skills in his pups. Scientists at the German Center for Neurodegenerative Diseases (DZNE) showed that male rodents fed a diet rich in folic acid (a B vitamin known as folate), methionine (important to the growth of new blood vessels, and a supplement used in many nerve disorders, including depression) and vitamin B12 (a water-soluble vitamin key in normal function of the brain and nervous system, and formation of red blood cells), produced pups that did not perform well in memory tests.

The report appears in "Molecular Psychiatry".

"For a long time, it was assumed that paternal epigenetic marks are erased completely after the fusion of sperm and egg cells."

Dan Ehninger PhD, Director, Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

However, we now know that some part of dad's DNA methylation survives. Ehninger's team, including colleagues at Helmholtz Zentrum München and the Federal Institute for Drugs and Medical Devices, fed male mice a diet rich with donated methyl elements containing high concentrations of methionine, folic acid, vitamin B12, choline, betaine (which affects inflammation in blood vessels) and zinc. A second group of male mice was fed the standard mouse diet of pellets formulated just for them.

After six weeks, the mice were mated with female mice and the resulting pups analyzed. Results showed pups of male mice fed with increased methyl donor elements performed poorly in learning and memory tests.

"We were able to show that even a transient change in paternal diet can impair learning skills in offspring. This affected in particular the ability to properly learn a spatial navigation task."

Dan Ehninger PhD

Nerve connections in the hippocampus were also affected. The hippocampus is important for memory. However, hippocampal nerves reacted sluggishly to electric stimuli. Their nerve plasticity or "reactivenes" was impaired. A gene called "Kcnmb2" involved in neuroplasticity, is lower in pups of fathers eating a diet rich in methyl changing elements.

Humans can also be exposed to high doses of methyl donor elements, says Ehninger. Particularly in countries like the USA, where foods are fortified with folic acid in breads and cereals, even cold lozengers are fortified with zinc. You may not be aware of how much of a particular methyl element you are getting from a part of your diet.

"Methyl donor deficiencies are well known to have adverse health consequences that can be prevented with diet supplements. However, our study suggests that their excessive consumption may be associated with adverse effects as well,"
explains Ehninger.

Ehninger wants to confirm whether epigenetic traits are also passed on by humans to their offspring, and then isolate which environmental factors have an influence. Does a father's age alter DNA methylation patterns? "To date, such epigenetic mechanisms and their intergenerational influences have certainly received too little attention," says Ehninger.

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.

Original Publication
"A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice", Devon P. Ryan et al., Molecular Psychiatry, DOI: 10.1038/MP.2017.53

Additional relevant material
Turning epigenetic marks OFF!
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Apr 6, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   

A father mouse's diet also affects the health of his offspring.
Image Credit: University of California Irvine research


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