PMID- 10676853 OWN - NLM STAT- MEDLINE DCOM- 20000302 LR - 20220310 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 36 IP - 3 DP - 2000 Mar TI - Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF). PG - 197-202 AB - 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. FAU - Mossner, R AU - Mossner R AD - Department of Psychiatry, University of Wurzburg, Germany. FAU - Daniel, S AU - Daniel S FAU - Albert, D AU - Albert D FAU - Heils, A AU - Heils A FAU - Okladnova, O AU - Okladnova O FAU - Schmitt, A AU - Schmitt A FAU - Lesch, K P AU - Lesch KP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (SLC6A4 protein, human) RN - 0 (Serotonin Plasma Membrane Transport Proteins) RN - 333DO1RDJY (Serotonin) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Alleles MH - B-Lymphocytes/*metabolism MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Carrier Proteins/genetics/*physiology MH - Cell Line, Transformed MH - Gene Expression MH - Genotype MH - Herpesvirus 4, Human MH - Humans MH - Membrane Glycoproteins/genetics/*physiology MH - *Membrane Transport Proteins MH - Nerve Growth Factor/*pharmacology MH - *Nerve Tissue Proteins MH - Neuroblastoma/metabolism MH - Polymorphism, Genetic MH - Promoter Regions, Genetic MH - Receptor, trkA/genetics/physiology MH - Receptor, trkB/genetics/physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serotonin/metabolism MH - Serotonin Plasma Membrane Transport Proteins MH - Tumor Cells, Cultured EDAT- 2000/02/17 09:00 MHDA- 2000/03/04 09:00 CRDT- 2000/02/17 09:00 PHST- 2000/02/17 09:00 [pubmed] PHST- 2000/03/04 09:00 [medline] PHST- 2000/02/17 09:00 [entrez] AID - S0197-0186(99)00122-9 [pii] AID - 10.1016/s0197-0186(99)00122-9 [doi] PST - ppublish SO - Neurochem Int. 2000 Mar;36(3):197-202. doi: 10.1016/s0197-0186(99)00122-9.