Maternal care modulates stress response and genome remodeling
Epigenetics not only supplements social neuroscience by highlighting the molecular mechanisms that orchestrate brain plasticity and memory formation, but also seek to blur any residual distinction between biology and social/ecological context. The first model of the cognitive brain was that of a computing machine, entirely severed from environmental influences, and the brain of social neuroscience still oscillates between plastic change and hardwiring metaphors, with the rise of what can be named the “Epigenetic Brain” or neuroepigentics research the reciprocal penetration of the social and the biological reaches a point where trying to establish any residual distinction seems increasingly hopeless( Meloni, 2014).
Meloni, M. (2014). The social brain meets the reactive genome: neuroscience, epigenetics and the new social biology. Frontiers in Human Neuroscience, 8: 1-1. doi:10.3389/ fnhum. 2014.00309
Working model for the effect of maternal care (specifically, of licking and grooming pups) on the epigenetic regulation of the expression of Nr3c1, the gene that encodes the glucocorticoid receptor (GR). Licking and grooming of pups activates thyroid hormone-dependent increases in hippocampal serotonin(5-hydroxytryptamine or 5-HT) levels and 5-HT binding to the 5-HT7 receptor. Activation of the 5-HT7receptor leads to the activation of a cyclic AMP–protein kinase A (PKA) cascade that induces the expression of the transcription factor nerve growth factor-inducible A (NGFiA) and cyclic AMP response element-binding (cReB) protein (cBP) expression and their association with the nonspecific exon 17 GR gene promoter.
In a new study, it was understood that, when neglected by their mothers, they triggered the formation of genes that jumped in brain cells. It is thought that this research may help explain the development of some neurological disorders seen in humans. "We are taught that our DNA is constantly stable, something that makes us what we are, but it is actually more dynamic," says geneticist Fred Gage at the Salk Institute in California. Tracy Bedrosian and Gage together watched the offspring and their mothers for two weeks to see how an array called the LINE-1 (long interspersed elements) retrotransposon replicated and replaced the rat pups in their hippocampal cells. When analyzing hippocampal cells of rat pups, LINE-1 copies were less labeled with a methyl group undergoing epigenetic regulation, unlike other transposons. "This finding is consistent with studies of childhood neglect that show altered patterns of DNA methylation for other genes," Gage said. "It's promising, because once you understand an instrument, you can start to develop methods for intervention." For now, this only helps us to understand that the events we experience in childhood are so gentle as to be effective at the gene level. With future work, we will find out exactly what this means.
The discovery of transposons starts with Barbara McClintock who eentually received the Nobel prize for this work.
Our genes are islands in a sea of transposable elements.
A variety of mutations contribute to somatic mosaicism, including indels, copy number variants (CNVs), aneuploidy, retrotransposition, and single nucleotide polymorphisms (SNPs). The brain is a genomic mosaic owing to somatic mutations that arise throughout development. Mobile genetic elements, including retrotransposons, are one source of somatic mosaicism in the brain. Retrotranspositionmay represent a form of plasticity in response to experience.
We divided mice into two groups based on median total maternal behavior, which revealed two maternal styles-high/low maternal care.
At weaning on postnatal day (PND) 21, the total percent time dams spent on maternal care
was significantly correlated with L1 copy number measured in the hippocampus of their
offspring (Fig. 1C) but not in the frontal cortex or heart.
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