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Serotonin transporter function, but not expression, is dependent on brain‐derived neurotrophic factor (BDNF): in vivo studies in BDNF‐deficient mice
Author(s) -
Daws L. C.,
Munn J. L.,
Valdez M. F.,
FrostoBurke T.,
Hensler J. G.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04392.x
Subject(s) - endocrinology , medicine , brain derived neurotrophic factor , neurotrophic factors , serotonin transporter , fluvoxamine , in vivo , hippocampus , neurotrophin , serotonin , tropomyosin receptor kinase b , chemistry , psychology , biology , receptor , fluoxetine , microbiology and biotechnology
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 ( T c ) increased markedly with age. In contrast, T c 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 ( V max ) 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 K T 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 [ 3 H]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.