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Exchange protein directly activated by cAMP 2 is required for corticotropin‐releasing hormone‐mediated spine loss
Author(s) -
Xie Zhong,
Penzes Peter,
Srivastava Deepak P.
Publication year - 2019
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14487
Subject(s) - dendritic spine , guanine nucleotide exchange factor , corticotropin releasing hormone , hormone , medicine , receptor , endocrinology , chemistry , microbiology and biotechnology , biology , signal transduction , hippocampal formation
Corticotropin‐releasing hormone is produced in response to acute and chronic stress. Previous studies have shown that activation of the corticotropin‐releasing hormone receptor 1 ( CRHR 1) by corticotropin‐releasing hormone results in the rapid loss of dendritic spines which correlates with cognitive dysfunction associated with stress. Exchange protein directly activated by cAMP ( EPAC 2), a guanine nucleotide exchange factor for the small GTP ase Rap, plays a critical role in regulating dendritic spine morphology and has been linked with CRHR 1 signalling. In this study, we have tested whether EPAC 2 links corticotropin‐releasing hormone with dendritic spine remodelling. In primary rat cortical neurons, we show that CRHR 1 is highly enriched in the dendritic spines. Furthermore, we find that EPAC 2 and CRHR 1 co‐localize in cortical neurons and that acute exposure to corticotropin‐releasing hormone induces spine loss. To establish whether EPAC 2 was required for corticotropin‐releasing hormone–mediated spine loss, we knocked‐down EPAC 2 in cortical neurons using a short hairpin RNA ‐mediated approach. In the presence of Epac2 knocked‐down, corticotropin‐releasing hormone was no longer able to induce spine loss. Taken together, our data indicate that EPAC 2 is required for the rapid loss of dendritic spines induced by corticotropin‐releasing hormone and may ultimately contribute to responses to acute stress.