PMID- 23805233
OWN - NLM
STAT- MEDLINE
DCOM- 20171006
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant 
      Effect of Genetic Deletion of P2X7 Receptors.
PG  - e66547
LID - 10.1371/journal.pone.0066547 [doi]
LID - e66547
AB  - Recent investigations have revealed that the genetic deletion of P2X7 receptors 
      (P2rx7) results in an antidepressant phenotype in mice. However, the link between 
      the deficiency of P2rx7 and changes in behavior has not yet been explored. In the 
      present study, we studied the effect of genetic deletion of P2rx7 on 
      neurochemical changes in the hippocampus that might underlie the antidepressant 
      phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility 
      in the tail suspension test (TST) and an attenuated anhedonia response in the 
      sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The 
      attenuated anhedonia was reproduced through systemic treatments with P2rx7 
      antagonists. The activation of P2rx7 resulted in the concentration-dependent 
      release of [(3)H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B 
      subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The 
      brain-derived neurotrophic factor (BDNF) expression was higher in saline but not 
      LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the 
      P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was 
      dependent on the activation of NMDA and non-NMDA receptors but not on Group I 
      metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine 
      (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- 
      mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower 
      in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of 
      [(3)H]5-HT and an elevated number of [(3)H]citalopram binding sites. The 
      LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion 
      there are several potential mechanisms for the antidepressant phenotype of 
      P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated 
      basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability 
      in the hippocampus.
FAU - Csolle, Cecilia
AU  - Csolle C
AD  - Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy 
      of Sciences, Budapest, Hungary.
FAU - Baranyi, Maria
AU  - Baranyi M
FAU - Zsilla, Gabriella
AU  - Zsilla G
FAU - Kittel, Agnes
AU  - Kittel A
FAU - Goloncser, Flora
AU  - Goloncser F
FAU - Illes, Peter
AU  - Illes P
FAU - Papp, Edit
AU  - Papp E
FAU - Vizi, E Sylvester
AU  - Vizi ES
FAU - Sperlagh, Beata
AU  - Sperlagh B
LA  - eng
GR  - P01 CA095616/CA/NCI NIH HHS/United States
GR  - U24 NS050606/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130621
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 333DO1RDJY (Serotonin)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 4P5DXU1F8Q (3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/analogs & derivatives/pharmacology
MH  - *Anhedonia
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dentate Gyrus/*metabolism/pathology/physiopathology
MH  - *Gene Deletion
MH  - Glutamic Acid/*metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - Mice, Knockout
MH  - *Neurogenesis
MH  - Receptors, Purinergic P2X7/*deficiency
MH  - Serotonin/*metabolism
PMC - PMC3689833
COIS- Competing Interests: This study received funding from the Gedeon Richter plc 
      (4700127848). This does not alter our adherence to all the PLOS ONE policies on 
      sharing data and materials.
EDAT- 2013/06/28 06:00
MHDA- 2013/06/28 06:01
PMCR- 2013/06/21
CRDT- 2013/06/28 06:00
PHST- 2012/06/22 00:00 [received]
PHST- 2013/05/13 00:00 [accepted]
PHST- 2013/06/28 06:00 [entrez]
PHST- 2013/06/28 06:00 [pubmed]
PHST- 2013/06/28 06:01 [medline]
PHST- 2013/06/21 00:00 [pmc-release]
AID - PONE-D-12-18427 [pii]
AID - 10.1371/journal.pone.0066547 [doi]
PST - epublish
SO  - PLoS One. 2013 Jun 21;8(6):e66547. doi: 10.1371/journal.pone.0066547. Print 2013.