Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF)

Neurochem Int. 2000 Mar;36(3):197-202. doi: 10.1016/s0197-0186(99)00122-9.


The serotonin transporter (5-HTT) regulates serotonergic neurotransmission by determining the magnitude and duration of serotonergic responses. We have recently described a polymorphism in the 5-HTT gene promoter (5-HTTLPR) which influences the function of the 5-HTT and is associated with several psychiatric disorders. Immortalized B lymphocytes express the 5-HTT, and a B lymphocyte line has been shown to express the receptor for brain-derived neurotrophic factor, trkB. Since brain-derived neurotrophic factor (BDNF) is a specific growth and differentiation factor for serotonergic neurons, we assessed whether BDNF is able to modulate 5-HTT function in B lymphoblasts. Nerve growth factor (NGF), another neurotrophin which acts via the trkA receptor, was also studied. Eight immortalized B lymphoblast lines were generated and genotyped for the 5-HTTLPR. After treatment with BDNF or NGF, 5-HT uptake and proliferation of the cell lines were assessed. Two of the B cell lines showed a dose-dependent reduction of 5-HT uptake after exposure to BDNF. Both of these cell lines were homozygous for the long allele of the 5-HTTLPR. NGF did not influence 5-HT uptake or cellular proliferation in any of the cell lines. Thus, BDNF but not NGF may influence 5-HT uptake in some B lymphocytes. The fact that regulation of the 5-HTT was observed preferentially in cells of the long/long genotype indicates that presence of a short allele confers reduced regulatory capacity on the 5-HTT. In conclusion, B lymphoblasts represent a practical model for functional regulation of the 5-HTT by neurotrophins in serotonergic neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • B-Lymphocytes / metabolism*
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Line, Transformed
  • Gene Expression
  • Genotype
  • Herpesvirus 4, Human
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Membrane Transport Proteins*
  • Nerve Growth Factor / pharmacology*
  • Nerve Tissue Proteins*
  • Neuroblastoma / metabolism
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Receptor, trkA / genetics
  • Receptor, trkA / physiology
  • Receptor, trkB / genetics
  • Receptor, trkB / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Tumor Cells, Cultured


  • Brain-Derived Neurotrophic Factor
  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Nerve Growth Factor
  • Receptor, trkA
  • Receptor, trkB