PMID- 17254018
OWN - NLM
STAT- MEDLINE
DCOM- 20070718
LR  - 20221207
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 101
IP  - 3
DP  - 2007 May
TI  - Serotonin transporter function, but not expression, is dependent on brain-derived 
      neurotrophic factor (BDNF): in vivo studies in BDNF-deficient mice.
PG  - 641-51
AB  - In the present study, we used high-speed chronoamperometry to examine serotonin 
      (5-HT) transporter (5-HTT) function in vivo in 2-, 5-, and 10-month-old 
      brain-derived neurotrophic factor (BDNF)+/- mice. The rate of clearance of 
      exogenously applied 5-HT was measured in CA3 region of hippocampus. In 
      2-month-old mice, the rate of 5-HT clearance did not differ between BDNF+/+ and 
      BDNF+/- mice. In BDNF+/+ mice, 5-HT clearance rate (Tc) increased markedly with 
      age. In contrast, Tc remained relatively static in BDNF+/- mice across 2-, 5-, 
      and 10-month age groups. At 5 months of age, female BDNF+/+ mice had a lower 
      maximal velocity (Vmax) for 5-HT clearance than male BDNF+/+ mice. There was a 
      similar trend in 5-month-old BDNF+/- mice, but this did not reach statistical 
      significance. There was an age-dependent increase in KT value for 5-HT clearance 
      (i.e., decreased in vivo affinity of 5-HTT), but no significant effect of 
      genotype or gender. 5-HTT density, as measured by [3H]cyanoimipramine binding, 
      was not different between BDNF+/+ and BDNF+/- mice, although there was a 
      significant increase in 5-HTT binding with age. The selective 5-HT reuptake 
      inhibitor fluvoxamine (50 and 100 pmol) significantly decreased 5-HT clearance in 
      BDNF+/+ mice, but not in BDNF+/- mice. Our data suggest that the profoundly 
      reduced ability of 5- and 10-month-old BDNF+/- mice to clear 5-HT is not because 
      of a decrease in the total number of 5-HTTs, but may be due to functional 
      deficits in the 5-HTT, e.g., in the machinery/signaling required for insertion of 
      5-HTTs into the plasma membrane and/or activation of the 5-HTT once it is 
      positioned to take up 5-HT from extracellular fluid.
FAU - Daws, L C
AU  - Daws LC
AD  - Department of Physiology, University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas 78229-3900, USA.
FAU - Munn, J L
AU  - Munn JL
FAU - Valdez, M F
AU  - Valdez MF
FAU - Frosto-Burke, T
AU  - Frosto-Burke T
FAU - Hensler, J G
AU  - Hensler JG
LA  - eng
GR  - R01-MH52369/MH/NIMH NIH HHS/United States
GR  - R01-MH64489/MH/NIMH NIH HHS/United States
GR  - R21 MH071488/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070124
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 02MNR4P2PM (cianopramine)
RN  - 333DO1RDJY (Serotonin)
RN  - O4L1XPO44W (Fluvoxamine)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Autoradiography/methods
MH  - Brain-Derived Neurotrophic Factor/deficiency/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Electrochemistry/methods
MH  - Female
MH  - Fluvoxamine/pharmacology
MH  - Gene Expression/drug effects/*physiology
MH  - Hippocampus/drug effects/metabolism
MH  - Imipramine/analogs & derivatives/pharmacokinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Protein Binding/drug effects
MH  - Serotonin/metabolism/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins/*physiology
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
MH  - Sex Factors
EDAT- 2007/01/27 09:00
MHDA- 2007/07/19 09:00
CRDT- 2007/01/27 09:00
PHST- 2007/01/27 09:00 [pubmed]
PHST- 2007/07/19 09:00 [medline]
PHST- 2007/01/27 09:00 [entrez]
AID - JNC4392 [pii]
AID - 10.1111/j.1471-4159.2006.04392.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 May;101(3):641-51. doi: 10.1111/j.1471-4159.2006.04392.x. Epub 
      2007 Jan 24.