HEALTH NEWS

Study Title:

Mom's Emotional Support Guides Healthy Gene Settings in Offspring

Study Abstract

Parenting and the early environment influence the risk for various psychopathologies. Studies in the rat suggest that variations in maternal care stably influence DNA methylation, gene expression, and neural function in the offspring. Maternal care affects neural development, including the GABAergic system, the function of which is linked to the pathophysiology of diseases including schizophrenia and depression. Postmortem studies of human schizophrenic brains have revealed decreased forebrain expression of glutamic acid decarboxylase 1 (GAD1) accompanied by increased methylation of a GAD1 promoter. We examined whether maternal care affects GAD1 promoter methylation in the hippocampus of adult male offspring of high and low pup licking/grooming (high-LG and low-LG) mothers. Compared with the offspring of low-LG mothers, those reared by high-LG dams showed enhanced hippocampal GAD1 mRNA expression, decreased cytosine methylation, and increased histone 3–lysine 9 acetylation (H3K9ac) of the GAD1 promoter. DNA methyltransferase 1 expression was significantly higher in the offspring of low- compared with high-LG mothers. Pup LG increases hippocampal serotonin (5-HT) and nerve growth factor-inducible factor A (NGFI-A) expression. Chromatin immunoprecipitation assays revealed enhanced NGFI-A association with and H3K9ac of the GAD1 promoter in the hippocampus of high-LG pups after a nursing bout. Treatment of hippocampal neuronal cultures with either 5-HT or an NGFI-A expression plasmid significantly increased GAD1 mRNA levels. The effect of 5-HT was blocked by a short interfering RNA targeting NGFI-A. These results suggest that maternal care influences the development of the GABA system by altering GAD1 promoter methylation levels through the maternally induced activation of NGFI-A and its association with the GAD1 promoter.

From press release:

Early life stress, such as an extreme lack of parental affection, has lasting effects on a gene important to normal brain processes and also tied to mental disorders, according to a new animal study in the Sept. 29 issue of The Journal of Neuroscience.

In the last decade, researchers have found evidence that experiences can alter the form and structure of DNA, an effect known as epigenetics. Because these changes affect genes, events early in life have the potential to make a lasting impact on behavior and health. Recent studies focused on cancer and obesity have already shown the power of epigenetics.

In a study led by Tie-Yuan Zhang, PhD, of McGill University, researchers investigated whether these changes might apply to the activity of genes in brain regions that control neural function and mental health. The authors explored how differences in a mother's attention affect the GAD1 gene, which controls the production of a chemical vital to brain cell communication called GABA. Research indicates that GABA helps to regulate emotion, and that people with schizophrenia may have GABA deficits.

The authors studied the maternal behavior of rats specifically bred to be either extremely caring or rarely affectionate. They found when the baby rats that were seldom touched grew up, specific regions of the DNA that controls the GAD1 gene were obstructed, likely leading to smaller amounts of GABA. On the other hand, adult rats coddled in the extreme as pups showed increased GAD1 gene production.

"A critical feature for the effect on gene GAD1 is that the immediate influence of maternal care is limited to a short period following birth, but the resulting changes are long-lasting, even into adulthood," Zhang said.

These findings suggest that the early life environment can drive molecular changes that affect brain function and might determine a child's predisposition to mental illness.

"We already knew that maternal care determined the stress responses of an offspring through a similar process, but this is the first time maternal care has been shown to link, via epigenetics, with a key enzyme that causes a major human disorder," said Jonathan Seckl, MD, PhD, of The University of Edinburgh, and an expert on the molecular process of hormones.

Study Information

Tie-Yuan Zhang, Ian C. Hellstrom, Rosemary C. Bagot, Xianglan Wen, Josie Diorio, and Michael J. Meaney.
Maternal Care and DNA Methylation of a Glutamic Acid Decarboxylase 1 Promoter in Rat Hippocampus.
J. Neurosci.
2010 September
1Sackler Program for Epigenetics and Developmental Psychobiology at McGill University