PMID- 18825147
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20220331
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 15
IP  - 5
DP  - 2010 May
TI  - Glial pathology in an animal model of depression: reversal of stress-induced 
      cellular, metabolic and behavioral deficits by the glutamate-modulating drug 
      riluzole.
PG  - 501-11
LID - 10.1038/mp.2008.106 [doi]
AB  - Growing evidence indicates that glia pathology and amino-acid neurotransmitter 
      system abnormalities contribute to the pathophysiology and possibly the 
      pathogenesis of major depressive disorder. This study investigates changes in 
      glial function occurring in the rat prefrontal cortex (PFC) after chronic 
      unpredictable stress (CUS), a rodent model of depression. Furthermore, we 
      analyzed the effects of riluzole, a Food and Drug Administration-approved drug 
      for the treatment of amyotrophic laterosclerosis, known to modulate glutamate 
      release and facilate glutamate uptake, on CUS-induced glial dysfunction and 
      depressive-like behaviors. We provide the first experimental evidence that 
      chronic stress impairs cortical glial function. Animals exposed to CUS and 
      showing behavioral deficits in sucrose preference and active avoidance exhibited 
      significant decreases in 13C-acetate metabolism reflecting glial cell metabolism, 
      and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The 
      cellular, metabolic and behavioral alterations induced by CUS were reversed 
      and/or blocked by chronic treatment with the glutamate-modulating drug riluzole. 
      The beneficial effects of riluzole on CUS-induced anhedonia and helplessness 
      demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment 
      also reversed CUS-induced reductions in glial metabolism and GFAP mRNA 
      expression. Our results are consistent with recent open-label clinical trials 
      showing the drug's effect in mood and anxiety disorders. This study provides 
      further validation of hypothesis that glial dysfunction and disrupted amino-acid 
      neurotransmission contribute to the pathophysiology of depression and that 
      modulation of glutamate metabolism, uptake and/or release represent viable 
      targets for antidepressant drug development.
FAU - Banasr, M
AU  - Banasr M
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, CT 
      06437, USA.
FAU - Chowdhury, G M I
AU  - Chowdhury GM
FAU - Terwilliger, R
AU  - Terwilliger R
FAU - Newton, S S
AU  - Newton SS
FAU - Duman, R S
AU  - Duman RS
FAU - Behar, K L
AU  - Behar KL
FAU - Sanacora, G
AU  - Sanacora G
LA  - eng
GR  - K02 MH076222-05/MH/NIMH NIH HHS/United States
GR  - R01 MH081211-05/MH/NIMH NIH HHS/United States
GR  - P01 MH025642/MH/NIMH NIH HHS/United States
GR  - R01 MH081211/MH/NIMH NIH HHS/United States
GR  - K02 MH076222/MH/NIMH NIH HHS/United States
GR  - R37 MH045481/MH/NIMH NIH HHS/United States
GR  - R37 MH045481-21/MH/NIMH NIH HHS/United States
GR  - P01 MH025642-32/MH/NIMH NIH HHS/United States
GR  - R01 DK027121-28S1/DK/NIDDK NIH HHS/United States
GR  - R01 MH045481/MH/NIMH NIH HHS/United States
GR  - R01 DK027121/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20080930
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Acetates)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Isotopes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sweetening Agents)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 57-50-1 (Sucrose)
RN  - 7LJ087RS6F (Riluzole)
SB  - IM
MH  - Acetates/blood
MH  - Animals
MH  - Avoidance Learning/drug effects
MH  - Behavioral Symptoms/*drug therapy/etiology
MH  - *Depression/drug therapy/etiology/pathology
MH  - Disease Models, Animal
MH  - Food Preferences/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Glial Fibrillary Acidic Protein/genetics/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Isotopes/metabolism
MH  - Magnetic Resonance Spectroscopy/methods
MH  - Male
MH  - Neuroglia/*drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*administration & dosage
MH  - Prefrontal Cortex/diagnostic imaging/pathology
MH  - RNA, Messenger/metabolism
MH  - Radionuclide Imaging
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Riluzole/*administration & dosage
MH  - Statistics, Nonparametric
MH  - Stress, Psychological/complications
MH  - Sucrose/administration & dosage
MH  - Sweetening Agents/administration & dosage
PMC - PMC3347761
MID - NIHMS306854
EDAT- 2008/10/01 09:00
MHDA- 2010/08/11 06:00
PMCR- 2012/05/08
CRDT- 2008/10/01 09:00
PHST- 2008/10/01 09:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
PHST- 2008/10/01 09:00 [entrez]
PHST- 2012/05/08 00:00 [pmc-release]
AID - mp2008106 [pii]
AID - 10.1038/mp.2008.106 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2010 May;15(5):501-11. doi: 10.1038/mp.2008.106. Epub 2008 Sep 
      30.