Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF).
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.
Mössner
R
R
Department of Psychiatry, University of Würzburg, Germany.
Daniel
S
S
Albert
D
D
Heils
A
A
Okladnova
O
O
Schmitt
A
A
Lesch
K P
KP
D000483:Alleles; D001402:B-Lymphocytes / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D015870:Gene Expression; D005838:Genotype; D004854:Herpesvirus 4, Human; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009447:Neuroblastoma / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D020917:Receptor, trkA / Q000235:genetics / Q000502:physiology; D020813:Receptor, trkB / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB