Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): In vivo studies in BDNF-deficient mice

L. C. Daws, J. L. Munn, M. F. Valdez, T. Frosto-Burke, J. G. Hensler

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)641-651
Number of pages11
JournalJournal of neurochemistry
Volume101
Issue number3
DOIs
StatePublished - May 2007

Keywords

  • Fluvoxamine
  • High-speed chronoamperometry
  • Hippocampus
  • Quantitative autoradiography

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): In vivo studies in BDNF-deficient mice'. Together they form a unique fingerprint.

Cite this