PMID- 22377193
OWN - NLM
STAT- MEDLINE
DCOM- 20130117
LR  - 20120814
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 22
IP  - 9
DP  - 2012 Sep
TI  - Hippocampus-specific deletion of tissue plasminogen activator "tPA" in adult mice 
      impairs depression- and anxiety-like behaviors.
PG  - 672-82
LID - 10.1016/j.euroneuro.2012.01.008 [doi]
AB  - Anxiety and depression are multifactorial disorders that have become prominent 
      health problems all over the world. Neurotrophic factors have emerged underlying 
      pathogenesis of these diseases. Although a number of studies indicate that the 
      hippocampus-brain-derived neurotrophic factor (BDNF) may be involved in these 
      psychiatric illnesses, little is known about the molecular mediators of these 
      disorders. In this study we further investigate the role of tissue plasminogen 
      activator (tPA), a serine protease involved in pro-BDNF cleavage to BDNF, in 
      depression and anxiety-like behaviors in adult mice. To address this issue, we 
      investigated the effect of hippocampus tPA manipulation, using viral vectors, on 
      anxiety- and depression-like behaviors, including the marble burying test (MBT), 
      elevated plus maze (EPM), tail suspension test (TST), novelty suppressed feeding 
      (NSF) and forced swim test (FST). Our results showed that tPA knock-down - using 
      lentiviral vectors expressing specific short hairpin RNAs (LV-shRNA) - increased 
      the number of buried marbles together with the digging time in the MBT and 
      decreased the time spent in open the arms of an EPM. In addition, tPA-knock down 
      in the hippocampus increased immobility in the FST and TST, and increased time to 
      feed in the NSF test. These effects were reversed when tPA-over-expressing 
      vectors (LV-tPA) were injected in the hippocampus. We also found that BDNF 
      protein levels were elevated in the hippocampus of mice receiving tPA-expressing 
      vectors. Together, our results imply that tPA manipulation may provide an 
      effective therapeutic intervention for depression and anxiety disorders.
CI  - Copyright (c) 2012 Elsevier B.V. and ECNP. All rights reserved.
FAU - Bahi, Amine
AU  - Bahi A
AD  - Department of Anatomy, Tawam Medical Campus, United Arab Emirates University, Al 
      Ain, United Arab Emirates. amine.bahi@uaeu.ac.ae
FAU - Dreyer, Jean-Luc
AU  - Dreyer JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120228
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Anxiety/*enzymology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Depression/*enzymology
MH  - Disease Models, Animal
MH  - Gene Transfer Techniques/psychology
MH  - Genetic Vectors/administration & dosage
MH  - Hippocampus/drug effects/*enzymology
MH  - Lentivirus/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microinjections
MH  - RNA, Small Interfering/administration & dosage/genetics/pharmacology
MH  - Stress, Psychological/*enzymology
MH  - Tissue Plasminogen Activator/*metabolism
MH  - Urokinase-Type Plasminogen Activator/metabolism
EDAT- 2012/03/02 06:00
MHDA- 2013/01/18 06:00
CRDT- 2012/03/02 06:00
PHST- 2011/10/12 00:00 [received]
PHST- 2011/12/12 00:00 [revised]
PHST- 2012/01/12 00:00 [accepted]
PHST- 2012/03/02 06:00 [entrez]
PHST- 2012/03/02 06:00 [pubmed]
PHST- 2013/01/18 06:00 [medline]
AID - S0924-977X(12)00026-0 [pii]
AID - 10.1016/j.euroneuro.2012.01.008 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2012 Sep;22(9):672-82. doi: 
      10.1016/j.euroneuro.2012.01.008. Epub 2012 Feb 28.