PMID- 12504924
OWN - NLM
STAT- MEDLINE
DCOM- 20030321
LR  - 20190726
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 43
IP  - 7
DP  - 2002 Dec
TI  - Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent 
      cortical neurons: an essential step for neuroprotection against glutamate 
      excitotoxicity.
PG  - 1173-9
AB  - Mechanisms underlying the therapeutic effects of lithium for bipolar mood 
      disorder remain poorly understood. Recent studies demonstrate that lithium has 
      neuroprotective actions against a variety of insults in vitro and in vivo. This 
      study was undertaken to investigate the role of the brain-derived neurotrophic 
      factor (BDNF)/TrkB signaling pathway in mediating neuroprotection of lithium 
      against glutamate excitotoxicity in cortical neurons. Pretreatment with either 
      lithium or BDNF protected rat cerebral cortical neurons from glutamate 
      excitotoxicity. The duration of treatment required to elicit maximal 
      neuroprotection by BDNF (1 day) was much shorter than that by lithium (6 days). 
      K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody 
      suppressed the neuroprotective effect of lithium. Treatment of cortical neurons 
      with lithium increased the cellular BDNF content in 3 days and the 
      phosphorylation of TrkB at Tyr490 in 5 days, suggesting that long-term lithium 
      administration enhances BDNF expression/secretion, leading to the activation of 
      TrkB receptor. Lithium failed to protect against glutamate excitotoxicity in 
      cortical neurons derived from homozygous and heterozygous BDNF knockout mice, 
      although lithium fully protected cortical neurons prepared from wild type mice 
      littermates. Taken together, these data suggest that the BDNF/TrkB pathway plays 
      an essential role in mediating the neuroprotective effect of lithium.
FAU - Hashimoto, Ryota
AU  - Hashimoto R
AD  - Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National 
      Institute of Mental Health, National Institutes of Health, Bethesda, MD 
      20892-1363, USA.
FAU - Takei, Nobuyuki
AU  - Takei N
FAU - Shimazu, Kazuhiro
AU  - Shimazu K
FAU - Christ, Lori
AU  - Christ L
FAU - Lu, Bai
AU  - Lu B
FAU - Chuang, De-Maw
AU  - Chuang DM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Neuroprotective Agents)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/metabolism/pathology
MH  - Excitatory Amino Acid Agonists/toxicity
MH  - Glutamic Acid/*toxicity
MH  - Lithium Chloride/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Neuroprotective Agents/metabolism/pharmacology
MH  - Rats
MH  - Receptor, trkB/*metabolism
MH  - Signal Transduction/drug effects/physiology
EDAT- 2002/12/31 04:00
MHDA- 2003/03/22 04:00
CRDT- 2002/12/31 04:00
PHST- 2002/12/31 04:00 [pubmed]
PHST- 2003/03/22 04:00 [medline]
PHST- 2002/12/31 04:00 [entrez]
AID - S0028390802002174 [pii]
AID - 10.1016/s0028-3908(02)00217-4 [doi]
PST - ppublish
SO  - Neuropharmacology. 2002 Dec;43(7):1173-9. doi: 10.1016/s0028-3908(02)00217-4.