PMID- 24301646
OWN - NLM
STAT- MEDLINE
DCOM- 20140605
LR  - 20211021
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 3
IP  - 12
DP  - 2013 Dec 3
TI  - Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal 
      cognitive dysfunction.
PG  - e328
LID - 10.1038/tp.2013.104 [doi]
AB  - Recent genetic studies have linked mental illness to alterations in disrupted in 
      schizophrenia 1 (DISC1), a multifunctional scaffolding protein that regulates 
      cyclic adenosine monophosphate (cAMP) signaling via interactions with 
      phosphodiesterase 4 (PDE4). High levels of cAMP during stress exposure impair 
      function of the prefrontal cortex (PFC), a region gravely afflicted in mental 
      illness. As stress can aggravate mental illness, genetic insults to DISC1 may 
      worsen symptoms by increasing cAMP levels. The current study examined whether 
      viral knockdown (KD) of the Disc1 gene in rat PFC increases susceptibility to 
      stress-induced PFC dysfunction. Rats were trained in a spatial working memory 
      task before receiving infusions of (a) an active viral construct that knocked 
      down Disc1 in PFC (DISC1 KD group), (b) a 'scrambled' construct that had no 
      effect on Disc1 (Scrambled group), or (c) an active construct that reduced DISC1 
      expression dorsal to PFC (Anatomical Control group). Data were compared with an 
      unoperated Control group. Cognitive performance was assessed following mild 
      restraint stress that had no effect on normal animals. DISC1 KD rats were 
      impaired by 1  h restraint stress, whereas Scrambled, Control, and Anatomical 
      Control groups were unaffected. Thus, knocking down Disc1 in PFC reduced the 
      threshold for stress-induced cognitive dysfunction, possibly through disinhibited 
      cAMP signaling at neuronal network synapses. These findings may explain why 
      patients with DISC1 mutations may be especially vulnerable to the effects of 
      stress.
FAU - Gamo, N J
AU  - Gamo NJ
AD  - Department of Neurobiology, Yale University, New Haven, CT, USA.
FAU - Duque, A
AU  - Duque A
FAU - Paspalas, C D
AU  - Paspalas CD
FAU - Kata, A
AU  - Kata A
FAU - Fine, R
AU  - Fine R
FAU - Boven, L
AU  - Boven L
FAU - Bryan, C
AU  - Bryan C
FAU - Lo, T
AU  - Lo T
FAU - Anighoro, K
AU  - Anighoro K
FAU - Bermudez, L
AU  - Bermudez L
FAU - Peng, K
AU  - Peng K
FAU - Annor, A
AU  - Annor A
FAU - Raja, A
AU  - Raja A
FAU - Mansson, E
AU  - Mansson E
FAU - Taylor, S R
AU  - Taylor SR
FAU - Patel, K
AU  - Patel K
FAU - Simen, A A
AU  - Simen AA
FAU - Arnsten, A F T
AU  - Arnsten AF
LA  - eng
GR  - P01 AG030004/AG/NIA NIH HHS/United States
GR  - T32 NS07224/NS/NINDS NIH HHS/United States
GR  - U54RR024350/RR/NCRR NIH HHS/United States
GR  - RL1 AA017536/AA/NIAAA NIH HHS/United States
GR  - 1RL1AA017536/AA/NIAAA NIH HHS/United States
GR  - T32 NS007224/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131203
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Disc1 protein, rat)
RN  - 0 (Nerve Tissue Proteins)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Cognition Disorders/etiology/genetics/*metabolism
MH  - Cyclic AMP/metabolism
MH  - Disease Models, Animal
MH  - Gene Knockdown Techniques
MH  - Male
MH  - Memory, Short-Term/*physiology
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Prefrontal Cortex/metabolism/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Restraint, Physical
MH  - Schizophrenia/complications/genetics/*metabolism
MH  - Signal Transduction
MH  - Stress, Psychological/genetics/*metabolism
MH  - Synapses/metabolism
PMC - PMC4030323
EDAT- 2013/12/05 06:00
MHDA- 2014/06/06 06:00
PMCR- 2013/12/01
CRDT- 2013/12/05 06:00
PHST- 2012/07/25 00:00 [received]
PHST- 2013/10/05 00:00 [revised]
PHST- 2013/10/09 00:00 [accepted]
PHST- 2013/12/05 06:00 [entrez]
PHST- 2013/12/05 06:00 [pubmed]
PHST- 2014/06/06 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - tp2013104 [pii]
AID - 10.1038/tp.2013.104 [doi]
PST - epublish
SO  - Transl Psychiatry. 2013 Dec 3;3(12):e328. doi: 10.1038/tp.2013.104.