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

@article{citeulike:1218233, 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 (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.}, address = {Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.}, author = {Daws, L C C. and Munn, J L L. and Valdez, M F F. and Frosto-Burke, T and Hensler, J G G. }, citeulike-article-id = {1218233}, doi = {http://dx.doi.org/10.1111/j.1471-4159.2006.04392.x}, issn = {0022-3042}, journal = {J Neurochem}, keywords = {bdnf, genotype, serotonin\_transporter}, month = {January}, posted-at = {2007-04-09 21:13:24}, priority = {2}, title = {Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): in vivo studies in BDNF-deficient mice.}, url = {http://dx.doi.org/10.1111/j.1471-4159.2006.04392.x}, year = {2007} }

TY - JOUR ID - citeulike:1218233 L3 - citeulike-article-id:1218233 TI - Serotonin transporter function, but not expression, is dependent on brain-derived neurotrophic factor (BDNF): in vivo studies in BDNF-deficient mice. JF - J Neurochem AD - Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. SN - 0022-3042 N2 - 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. KW - bdnf KW - genotype KW - serotonin_transporter AU - Daws, L C AU - Munn, J L AU - Valdez, M F AU - Frosto-Burke, T AU - Hensler, J G PY - 2007/01/24/ UR - http://dx.doi.org/10.1111/j.1471-4159.2006.04392.x ER -