BEHAVIOR Mom Always Licked You Best

Rats raised by mothers that engage extensively in licking, grooming, and arched-back nursing (LG-ABN) grow up to be less fearful and less responsive to stress than do those raised by mothers that do not engage as frequently in these behaviors. These traits are accompanied by increased expression of glucocorticoid receptors (GRs) in the adult rat's hippocampus. LG-ABN elicits serotonergic activity and thereby activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A signaling pathway and expression of the transcription factor NGFI-A (nerve growth factor-inducible protein A). However, the mechanisms whereby enhanced signaling in the pup lead to molecular and behavioral changes in the adult remain unclear (see Sapolsky). Weaver et al. found reduced methylation of the region around the NGFI-A binding site of the GR promoter in DNA from hippocampal tissue of adult rats raised by highly LG-ABN mothers compared with that from rats raised by mothers that showed low levels of LG-ABN. Changes in methylation status were independent of biological relationship and appeared during the critical period for LG-ABN-induced behavioral changes. Chromatin immunoprecipitation analysis revealed increased histone H3-K9 acetylation and NGFI-A binding in hippocampal chromatin of adult offspring of highly LG-ABN mothers. Intracerebroventricular infusion of the histone deacetylase inhibitor trichostatin A (TSA) enhanced acetylation in offspring of mothers that showed low levels of LG-ABN and reduced methylation in both low and high LG-ABN offspring. Moreover, TSA enhanced GR expression and reduced adrenocortical responses to stress, so that low LG-ABN offspring were indistinguishable in these respects from high LG-ABN offspring. Thus, these enduring effects of maternal behavior appear to be mediated through changes in DNA methylation status and can be pharmacologically reversed.

I. C. G. Weaver, N. Cervoni, F. A. Champagne, A. C. D'Alessio, S. Sharma, J. R. Seckl, S. Dymov, M. Szyf, M. J. Meany, Epigenetic programming by maternal behavior. Nat. Neurosci. 7, 847-854 (2004). [Online Journal]

R. M. Sapolsky, Mothering style and methylation. Nat. Neurosci. 7, 791-792 (2004). [Online Journal]