PMID- 21783178
OWN - NLM
STAT- MEDLINE
DCOM- 20120612
LR  - 20210419
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 71
IP  - 4
DP  - 2012 Feb 15
TI  - Site-specific genetic manipulation of amygdala corticotropin-releasing factor 
      reveals its imperative role in mediating behavioral response to challenge.
PG  - 317-26
LID - 10.1016/j.biopsych.2011.05.036 [doi]
AB  - BACKGROUND: Faulty regulation of the central extrahypothalamic 
      corticotropin-releasing factor (CRF) expression is associated with stress-related 
      psychopathologies including anxiety disorders and depression. Extensive 
      pharmacological literature describes the effects of CRF agonists or antagonists' 
      administration on anxiety-like behavior. However, the relevance of the endogenous 
      agonist, presumed to be CRF, has never been explicitly demonstrated. Several 
      genetic models have been used to study the role of CRF in the physiological 
      response to stress and in stress-related disorders. Nevertheless, developmental 
      compensatory mechanisms and lack of spatial and temporal specificity limited the 
      interpretations of these studies. METHODS: Two lentiviral-based systems were 
      designed, generated, and used to knockdown (KD) or conditionally overexpress (OE) 
      CRF in the central amygdala (CeA) of adult mice. Behavioral responses associated 
      with the CeA, such as anxiety, depression and fear memory, and the plasma 
      corticosterone levels were evaluated under both basal and stressful conditions. 
      RESULTS: Changing the CeA-CRF levels mildly affected anxiety-like behaviors under 
      basal conditions. However, following exposure to an acute stressor, CeA-CRF-KD 
      strongly attenuated stress-induced anxiety-like behaviors, whereas a short-term 
      CeA-CRF-overexpression enhanced the stress-induced effects on these behaviors. 
      Interestingly, a significant increase in basal corticosterone levels in the 
      CeA-CRF-KD mice was observed, demonstrating the importance of endogenous CeA-CRF 
      levels for basal, but not stress-induced, corticosterone levels. CONCLUSIONS: 
      These results highlight the pivotal role of CeA CRF expression regulation in 
      mediating adequate behavioral responses to stress and introduce these novel viral 
      tools as a useful approach for dissecting the role of central CRF in mediating 
      behavioral and neuroendocrine responses to stress.
CI  - Copyright (c) 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Regev, Limor
AU  - Regev L
AD  - Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
FAU - Tsoory, Michael
AU  - Tsoory M
FAU - Gil, Shosh
AU  - Gil S
FAU - Chen, Alon
AU  - Chen A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110723
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Amygdala/*metabolism
MH  - Animals
MH  - Anxiety/etiology/*genetics/metabolism
MH  - Behavior, Animal/physiology
MH  - Corticosterone/metabolism
MH  - *Corticotropin-Releasing Hormone/genetics/metabolism
MH  - Depression/etiology/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Genetic Vectors
MH  - Lentivirus
MH  - Mice
MH  - Mice, Transgenic
MH  - Stress, Physiological/genetics
MH  - Stress, Psychological/complications/metabolism
EDAT- 2011/07/26 06:00
MHDA- 2012/06/13 06:00
CRDT- 2011/07/26 06:00
PHST- 2010/12/29 00:00 [received]
PHST- 2011/05/18 00:00 [revised]
PHST- 2011/05/27 00:00 [accepted]
PHST- 2011/07/26 06:00 [entrez]
PHST- 2011/07/26 06:00 [pubmed]
PHST- 2012/06/13 06:00 [medline]
AID - S0006-3223(11)00631-7 [pii]
AID - 10.1016/j.biopsych.2011.05.036 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2012 Feb 15;71(4):317-26. doi: 10.1016/j.biopsych.2011.05.036. 
      Epub 2011 Jul 23.