PMID- 11685390
OWN - NLM
STAT- MEDLINE
DCOM- 20020115
LR  - 20131121
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 158
IP  - 1
DP  - 2001 Oct
TI  - Chronic lithium treatment increases the expression of brain-derived neurotrophic 
      factor in the rat brain.
PG  - 100-6
AB  - RATIONALE: Lithium is the most widely prescribed mood stabilizer, but the precise 
      mechanism of lithium is unresolved. OBJECTIVE: We examine the effects of the 
      administration of therapeutically relevant concentrations of lithium on the 
      expression of brain-derived neurotrophic factor (BDNF) and its receptor, Trk B, 
      as well as glia-derived neurotrophic factor (GDNF) and its receptors, RET and 
      GDNFR-alpha, in the rat brain. In addition, we also examined the effect of 
      another well-prescribed mood stabilizer, valproate, on the expression of BDNF and 
      GDNF. METHODS: Rats were kept on a 0.2% lithium carbonate-containing diet for 1, 
      7, 14, or 28 days or treated with valproate (400 mg/kg per day i.p.) for 1 or 14 
      days. After the brains were rapidly removed, the levels of BDNF, GDNF, and their 
      receptors were measured by ELISA or western blot analysis. RESULTS: Chronic 
      lithium treatment for 14 and 28 days significantly increased the expression of 
      BDNF in the hippocampus and temporal cortex. In addition, chronic lithium 
      treatment for 14 days significantly increased the expression of BDNF in the 
      frontal cortex. In contrast, acute or chronic dietary lithium treatment did not 
      alter GDNF expression in these brain regions. In addition, acute or chronic 
      lithium treatments did not change the levels of Trk B, RET, or GDNFR-alpha 
      immunoreactivity. As well as lithium, repeated administration of valproate also 
      increased the expression of BDNF in the frontal cortex and hippocampus. 
      CONCLUSIONS: Our results suggest that the chronic administration of mood 
      stabilizers may produce a neurotrophic effect mediated by the upregulation of 
      BDNF in the rat brain.
FAU - Fukumoto, T
AU  - Fukumoto T
AD  - Department of Psychiatry and Neurosciences, Hiroshima University School of 
      Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
FAU - Morinobu, S
AU  - Morinobu S
FAU - Okamoto, Y
AU  - Okamoto Y
FAU - Kagaya, A
AU  - Kagaya A
FAU - Yamawaki, S
AU  - Yamawaki S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antimanic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antimanic Agents/*administration & dosage
MH  - Brain/*drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/metabolism
MH  - Frontal Lobe/drug effects/metabolism
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Hippocampus/drug effects/metabolism
MH  - Injections, Intraperitoneal
MH  - Lithium Chloride/*administration & dosage
MH  - Male
MH  - *Nerve Growth Factors
MH  - Nerve Tissue Proteins/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Temporal Lobe/drug effects/metabolism
EDAT- 2001/10/31 10:00
MHDA- 2002/01/16 10:01
CRDT- 2001/10/31 10:00
PHST- 2001/03/12 00:00 [received]
PHST- 2001/06/20 00:00 [accepted]
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/01/16 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
AID - 10.1007/s002130100871 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2001 Oct;158(1):100-6. doi: 10.1007/s002130100871.