PMID- 18047561
OWN - NLM
STAT- MEDLINE
DCOM- 20080506
LR  - 20131121
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 105
IP  - 2
DP  - 2008 Apr
TI  - BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 
      knockout mice.
PG  - 565-72
AB  - Stress can cause damage and atrophy of neurons in the hippocampus by deregulating 
      the expression of neurotrophic factors that promote neuronal plasticity. The 
      endocannabinoid system represents a physiological substrate involved in 
      neuroprotection at both cellular and emotional levels. The lack of CB1 receptor 
      alters neuronal plasticity and originates an anxiety-like phenotype in mice. In 
      the present study, CB1 knockout mice exhibited an augmented response to stress 
      revealed by the increased despair behavior and corticosterone levels showed in 
      the tail suspension test and decreased brain derived neurotrophic factor (BDNF) 
      levels in the hippocampus. Interestingly, local administration of BDNF in the 
      hippocampus reversed the increased despair behavior of CB1 knockout mice, 
      confirming the crucial role played by BDNF on the emotional impairment of these 
      mutants. The neurotrophic deficiency seems to be specific for BDNF as no 
      differences were found in the levels of nerve growth factor and NT-3, two 
      additional neurotrophic factors. Moreover, BDNF impairment is not related to the 
      activity of its specific tyrosine kinase receptor or the activity of the 
      transcription factor cAMP responsive element binding. These results suggest that 
      the lack of CB1 receptor originates an enhanced response to stress and deficiency 
      in neuronal plasticity by decreasing BDNF levels in the hippocampus that lead to 
      impairment in the responses to emotional disturbances.
FAU - Aso, Ester
AU  - Aso E
AD  - Grup de Recerca de Neurobiologia del Comportament (GRNC), Departament de Ciencies 
      Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, Barcelona, Spain.
FAU - Ozaita, Andres
AU  - Ozaita A
FAU - Valdizan, Elsa M
AU  - Valdizan EM
FAU - Ledent, Catherine
AU  - Ledent C
FAU - Pazos, Angel
AU  - Pazos A
FAU - Maldonado, Rafael
AU  - Maldonado R
FAU - Valverde, Olga
AU  - Valverde O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071128
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*metabolism
MH  - CREB-Binding Protein/metabolism
MH  - Corticosterone/blood
MH  - Freezing Reaction, Cataleptic/*physiology
MH  - Hindlimb Suspension/methods
MH  - Hippocampus/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Radioimmunoassay/methods
MH  - Receptor, Cannabinoid, CB1/*deficiency
MH  - Receptor, trkB/metabolism
MH  - Stress, Physiological/drug therapy/genetics/*pathology/*physiopathology
EDAT- 2007/12/01 09:00
MHDA- 2008/05/07 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/05/07 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - JNC5149 [pii]
AID - 10.1111/j.1471-4159.2007.05149.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Apr;105(2):565-72. doi: 10.1111/j.1471-4159.2007.05149.x. Epub 
      2007 Nov 28.