RT Journal Article
SR Electronic
T1 Postnatal Handling Increases the Expression of cAMP-Inducible Transcription Factors in the Rat Hippocampus: The Effects of Thyroid Hormones and Serotonin
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3926
OP 3935
DO 10.1523/JNEUROSCI.20-10-03926.2000
VO 20
IS 10
A1 Michael J. Meaney
A1 Josie Diorio
A1 Darlene Francis
A1 Shelley Weaver
A1 Joyce Yau
A1 Karen Chapman
A1 Jonathan R. Seckl
YR 2000
UL http://www.jneurosci.org/content/20/10/3926.abstract
AB Postnatal handling increases glucocorticoid receptor expression in the rat hippocampus, thus altering the regulation of hypothalamic synthesis of corticotropin-releasing hormone and the hypothalamic–pituitary–adrenal response to stress. The effect on glucocorticoid receptor gene expression represents one mechanism by which the early environment can exert a long-term effect on neural development. The handling effect on hippocampal glucocorticoid receptor expression is dependent on peripheral thyroid hormone release and the activation of ascending serotonergic pathways. In primary hippocampal cell cultures, serotonin (5-HT) increases glucocorticoid receptor expression, and this effect appears to be mediated by increased cAMP levels. In the current studies we examined the in vivoeffects of handling on hippocampal cAMP–protein kinase A (PKA) activity. In 7-d-old rat pups, we found that (1) postnatal handling increased adenylyl cyclase activity and hippocampal cAMP levels, (2) the effect of handling on cAMP levels was completely blocked by treatment with either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or the 5-HT receptor antagonist, ketanserin, and (3) handling also increased hippocampal PKA activity. We then examined the effects of handling on cAMP-inducible transcription factors. Handling rapidly increased levels of the mRNAs for nerve growth factor-inducible factor A (NGFI-A) (zif268,krox24) and activator protein-2 (AP-2) as well as for NGFI-A and AP-2 immunoreactivity throughout the hippocampus. Finally, we found that the effects of handling on NGFI-A and AP-2 expression were significantly reduced by concurrent treatment with either PTU or ketanserin, effects that paralleled those on cAMP formation. NGFI-A and AP-2 have been implicated in the regulation of glucocorticoid receptor expression during development. Thus, these findings suggest that postnatal handling might alter glucocorticoid receptor gene expression via cAMP–PKA pathways involving the activation of NGFI-A and AP-2.