PMID- 23632457
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20211021
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 3
IP  - 4
DP  - 2013 Apr 30
TI  - BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis 
      and elicits anxiolytic-like activities.
PG  - e253
LID - 10.1038/tp.2013.30 [doi]
AB  - The therapeutic activity of selective serotonin (5-HT) reuptake inhibitors 
      (SSRIs) relies on long-term adaptation at pre- and post-synaptic levels. The 
      sustained administration of SSRIs increases the serotonergic neurotransmission in 
      response to a functional desensitization of the inhibitory 5-HT1A autoreceptor in 
      the dorsal raphe. At nerve terminal such as the hippocampus, the enhancement of 
      5-HT availability increases brain-derived neurotrophic factor (BDNF) synthesis 
      and signaling, a major event in the stimulation of adult neurogenesis. In 
      physiological conditions, BDNF would be expressed at functionally relevant levels 
      in neurons. However, the recent observation that SSRIs upregulate BDNF mRNA in 
      primary cultures of astrocytes strongly suggest that the therapeutic activity of 
      antidepressant drugs might result from an increase in BDNF synthesis in this cell 
      type. In this study, by overexpressing BDNF in astrocytes, we balanced the ratio 
      between astrocytic and neuronal BDNF raising the possibility that such 
      manipulation could positively reverberate on anxiolytic-/antidepressant-like 
      activities in transfected mice. Our results indicate that BDNF overexpression in 
      hippocampal astrocytes produced anxiolytic-/antidepressant-like activity in the 
      novelty suppressed feeding in relation with the stimulation of hippocampal 
      neurogenesis whereas it did not potentiate the effects of the SSRI fluoxetine on 
      these parameters. Moreover, overexpressing BDNF revealed the anxiolytic-like 
      activity of fluoxetine in the elevated plus maze while attenuating 5-HT 
      neurotransmission in response to a blunted downregulation of the 5-HT1A 
      autoreceptor. These results emphasize an original role of hippocampal astrocytes 
      in the synthesis of BDNF, which can act through neurogenesis-dependent and 
      -independent mechanisms to regulate different facets of anxiolytic-like 
      responses.
FAU - Quesseveur, G
AU  - Quesseveur G
AD  - Laboratoire de Neuropharmacologie EA3544, Faculte de Pharmacie, Universite 
      Paris-Sud, Chatenay-Malabry Cedex, France.
FAU - David, D J
AU  - David DJ
FAU - Gaillard, M C
AU  - Gaillard MC
FAU - Pla, P
AU  - Pla P
FAU - Wu, M V
AU  - Wu MV
FAU - Nguyen, H T
AU  - Nguyen HT
FAU - Nicolas, V
AU  - Nicolas V
FAU - Auregan, G
AU  - Auregan G
FAU - David, I
AU  - David I
FAU - Dranovsky, A
AU  - Dranovsky A
FAU - Hantraye, P
AU  - Hantraye P
FAU - Hen, R
AU  - Hen R
FAU - Gardier, A M
AU  - Gardier AM
FAU - Deglon, N
AU  - Deglon N
FAU - Guiard, B P
AU  - Guiard BP
LA  - eng
GR  - R01 MH091844/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20130430
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology
MH  - Anxiety/drug therapy/metabolism/physiopathology
MH  - Astrocytes/drug effects/*metabolism/physiology
MH  - Behavior, Animal/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/analysis/*metabolism/physiology
MH  - Depression/drug therapy/metabolism/physiopathology
MH  - Fluoxetine/pharmacology
MH  - Gene Expression/physiology
MH  - Hippocampus/chemistry/drug effects/*metabolism/physiology
MH  - Male
MH  - Mice
MH  - Neurogenesis/*physiology
MH  - Piperazines/pharmacology
MH  - Pyridines/pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Serotonin Receptor Agonists/pharmacology
PMC - PMC3641417
EDAT- 2013/05/02 06:00
MHDA- 2013/12/24 06:00
PMCR- 2013/04/01
CRDT- 2013/05/02 06:00
PHST- 2013/05/02 06:00 [entrez]
PHST- 2013/05/02 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - tp201330 [pii]
AID - 10.1038/tp.2013.30 [doi]
PST - epublish
SO  - Transl Psychiatry. 2013 Apr 30;3(4):e253. doi: 10.1038/tp.2013.30.