Genes 2 Brains 2 Mind 2 Me

Image via Wikipedia The “Central Dogma” of molecular biology rightfully points out a somewhat one-way transfer of information from DNA to RNA to protein. This mechanism has obvious implications for evolution insofar as you are issued a newly shuffled genome at birth and must make the best of it – no cheating allowed by receiving the acquired levels of fitness of your parents – since these cannot be transmitted via the bare thread of DNA. This being the case, however, it is, of course, fun to encounter ways in which mother nature skirts the rules. The term ‘mother‘ is particularly apt to the work of Michael Meaney and colleagues in Montreal, who have for many years been teasing apart mechanisms underlying maternal care in mammals. It seems that when a female rat has been deprived of good mothering (copious licking & grooming are the traits of a good rat mom) they, themselves, also demonstrate poor mothering skills (sadly, daughters DO grow up to be their mothers). The Meany group provide a great review of the mechanisms of this seeming example of “inheritance of acquired characteristics” in their review, “Epigenetic Programming of Phenotypic Variations in Reproductive Strategies in the Rat Through Maternal Care” [DOI: 10.1111/j.1365-2826.2008.01725.x]. Apparently, this mode of inheritance is dependent on the early development of neuro-endocrine circuits that regulate emotional responsivity and are dependent on early, neonatal environmental stimulation (licking & grooming activate these developing circuits) – and is not dependent on the sperm/egg-bourne passage of a particular stretch of DNA. Interestingly though, the team demonstrates that genomic CpG hypermethylation of the estrogen receptor might serve as a mechanism to maintain the effect – at the level of the genome – of the mother’s poor parenting. Mom’s who were poorly cared for as infants may have a hypermethylated estrogen receptor and therefore are more likely to demonstrate poor parenting in adulthood as a result of the maintainence of this methylated (transcriptionally repressed) estrogen receptor. More interestingly, the team has recently begun to investigate this mechanism in humans, and reported that in post-mortem analysis of hippocampal tissue from individuals who experienced early life neglect and, tragically, suffered death from suicide, that there seems to be a similar type of hypermethylation. Their PLoS ONE article, “Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain” [DOI: 10.1371/journal.pone.0002085] provides an analysis of promoters of rRNA genes in the hippocampus – a brain region whose development and structure is negatively affected by environmental stress and neglect. This is a line of research that is interesting on many levels – from Lamarck to Freud. As a parent, the work shows how important it is to understand & appreciate the role of parenting and social welfare in mental health.

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