PMID- 24670989
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- 
      or NMDA-dependent mechanism?
PG  - e92416
LID - 10.1371/journal.pone.0092416 [doi]
LID - e92416
AB  - Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for 
      brain functioning. Since the demonstration that plasmin is able to process 
      pro-BDNF to mature BDNF and that these two forms have opposite effects on 
      neuronal survival and plasticity, a particular attention has been paid to the 
      link between tissue plasminogen activator (tPA)/plasmin system and BDNF 
      metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) 
      receptor subunits is also considered as a neuromodulator of glutamatergic 
      transmission. In this context, the aim of our study was to investigate the effect 
      of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the 
      hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive 
      increase in mature BDNF levels associated with TrkB activation. In order to 
      delineate the mechanistic involved, plasmin activity was assessed and its 
      inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA 
      receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with 
      rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA 
      administration failed to increase hippocampal plasmin activity suggesting that 
      the plasminogen/plasmin system is not involved whereas MK801 abrogated the 
      augmentation in mature BDNF levels observed after rt-PA administration. All 
      together, our results show that rt-PA administration induces increase in 
      hippocampal mature BDNF expression and suggests that rt-PA contributes to the 
      control of brain BDNF synthesis through a plasmin-independent potentiation of 
      NMDA receptors signaling.
FAU - Rodier, Marion
AU  - Rodier M
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, France; 
      Universite de Bourgogne, Dijon, France; Department of Neurology, University 
      Hospital, Dijon, France.
FAU - Prigent-Tessier, Anne
AU  - Prigent-Tessier A
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, France; 
      Universite de Bourgogne, Dijon, France.
FAU - Bejot, Yannick
AU  - Bejot Y
AD  - Department of Neurology, University Hospital, Dijon, France; Centre 
      d'Epidemiologie des Populations, EA4184, Dijon, France.
FAU - Jacquin, Agnes
AU  - Jacquin A
AD  - Department of Neurology, University Hospital, Dijon, France; Centre 
      d'Epidemiologie des Populations, EA4184, Dijon, France.
FAU - Mossiat, Claude
AU  - Mossiat C
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, France; 
      Universite de Bourgogne, Dijon, France.
FAU - Marie, Christine
AU  - Marie C
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, France; 
      Universite de Bourgogne, Dijon, France.
FAU - Garnier, Philippe
AU  - Garnier P
AD  - Unite INSERM U1093 Cognition, Action et Plasticite Sensorimotrice, Dijon, France; 
      Universite de Bourgogne, Dijon, France; Departement Genie Biologique, IUT, Dijon, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20140326
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (brain-derived neurotrophic factor precursor)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6T84R30KC1 (Tranexamic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.21.7 (Fibrinolysin)
SB  - IM
RIN - PLoS One. 2021 Aug 3;16(8):e0255763. PMID: 34343198
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Fibrinolysin/*metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Male
MH  - N-Methylaspartate/*metabolism
MH  - Protein Precursors/metabolism
MH  - Rats, Wistar
MH  - Receptor, trkB/metabolism
MH  - Tissue Plasminogen Activator/*administration & dosage/*pharmacology
MH  - Tranexamic Acid/pharmacology
PMC - PMC3966802
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/29 06:00
MHDA- 2015/12/17 06:00
PMCR- 2014/03/26
CRDT- 2014/03/28 06:00
PHST- 2013/09/30 00:00 [received]
PHST- 2014/02/21 00:00 [accepted]
PHST- 2014/03/28 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
PHST- 2014/03/26 00:00 [pmc-release]
AID - PONE-D-13-40113 [pii]
AID - 10.1371/journal.pone.0092416 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 26;9(3):e92416. doi: 10.1371/journal.pone.0092416. eCollection 
      2014.