PMID- 18547721
OWN - NLM
STAT- MEDLINE
DCOM- 20080926
LR  - 20181211
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 440
IP  - 1
DP  - 2008 Jul 25
TI  - Chronic treatment with a selective ligand for the sigma-1 receptor chaperone, 
      SA4503, up-regulates BDNF protein levels in the rat hippocampus.
PG  - 19-22
LID - 10.1016/j.neulet.2008.05.055 [doi]
AB  - Numerous studies have shown the sigma-1 receptor chaperone (previously designated 
      as the sigma-1 receptor) to play an important role in various neuronal functions, 
      and selective ligands for sigma-1 receptor chaperone have been found to have 
      therapeutic potential in certain psychiatric disorders and some forms of neuronal 
      damage. Brain-derived neurotrophic factor (BDNF) is postulated to be related to 
      the pharmacological action of sigma ligands, though the functional interaction 
      between sigma-1 receptor chaperone ligands and BDNF remains to be clarified. This 
      study was undertaken to investigate whether or not administration of SA4503, a 
      selective ligand for sigma-1 receptor chaperone, affects BDNF levels in several 
      regions of the rat brain. Rats were injected with SA4503 (0.3, 1 and 3 mg/(kg 
      day), i.p.) once or repeatedly for 2 or 4 weeks. BDNF protein levels were 
      estimated by Western blot analysis in the striatum, midbrain, frontal cortex, 
      hippocampus and thalamus. A single injection of SA4503 did not change BDNF 
      protein levels, while chronic injection for 2 or 4 weeks tended to increase BDNF 
      levels in the hippocampus. In particular, 1 mg/kg of SA4503 daily for 2 weeks led 
      to a statistically significant, i.e. twofold, increase in the BDNF protein level 
      in the hippocampus. On the other hand, the TrkB receptor, a primary receptor for 
      BDNF, exists in truncated and full-length isoforms, hippocampal levels of which 
      were unaffected by SA4503 treatments. Our findings indicate that chronic 
      administration of SA4503 may regulate region-specific BDNF functions in the rat 
      brain.
FAU - Kikuchi-Utsumi, Kazue
AU  - Kikuchi-Utsumi K
AD  - Department of Pharmacology, Teikyo University, School of Medicine, 2-11-1 Kaga, 
      Itabashi ward, Tokyo 173-8605, Japan.
FAU - Nakaki, Toshio
AU  - Nakaki T
LA  - eng
PT  - Journal Article
DEP - 20080521
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nootropic Agents)
RN  - 0 (Piperazines)
RN  - 9J7A4144BX (SA 4503)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Nootropic Agents/*pharmacology
MH  - Piperazines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
MH  - Up-Regulation/*drug effects
EDAT- 2008/06/13 09:00
MHDA- 2008/09/27 09:00
CRDT- 2008/06/13 09:00
PHST- 2008/02/19 00:00 [received]
PHST- 2008/05/14 00:00 [revised]
PHST- 2008/05/16 00:00 [accepted]
PHST- 2008/06/13 09:00 [pubmed]
PHST- 2008/09/27 09:00 [medline]
PHST- 2008/06/13 09:00 [entrez]
AID - S0304-3940(08)00704-0 [pii]
AID - 10.1016/j.neulet.2008.05.055 [doi]
PST - ppublish
SO  - Neurosci Lett. 2008 Jul 25;440(1):19-22. doi: 10.1016/j.neulet.2008.05.055. Epub 
      2008 May 21.