TY - JOUR
T1 - BDNF downregulates 5-HT(2A) receptor protein levels in hippocampal cultures
AU - Trajkovska, V
AU - Santini, M A
AU - Marcussen, Anders Bue
AU - Thomsen, Morten Skøtt
AU - Hansen, H H
AU - Mikkelsen, Jens D.
AU - Arneberg, L
AU - Kokaia, M
AU - Knudsen, G M
AU - Aznar, S
N1 - Keywords: Animals; Apoptosis; Blotting, Western; Brain-Derived Neurotrophic Factor; Cells, Cultured; Down-Regulation; Female; Hippocampus; Mice; Mice, Knockout; Nerve Tissue Proteins; Organ Culture Techniques; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Synapses
PY - 2009
Y1 - 2009
N2 - Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT(2A) receptor levels in hippocampus confirming the association between 5-HT(2A) receptor and BDNF levels in vivo. In conclusion, our results point to a regulatory role of BDNF on 5-HT2A receptor levels. This interaction may be an important mechanism in the role of BDNF in affective disorders emphasizing the need for further elucidating the specificity and the mechanism behind this regulation.
AB - Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT(2A)) have been related to depression pathology. Specific 5-HT(2A) receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT(2A) receptor level. Here we show a direct effect of BDNF on 5-HT(2A) receptor protein levels in primary hippocampal neuronal and mature hippocampal organotypic cultures exposed to different BDNF concentrations for either 1, 3, 5 or 7 days. In vivo effects of BDNF on hippocampal 5-HT(2A) receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50ng/mL BDNF resulted in downregulation of 5-HT(2A), but not of 5-HT(1A), receptor protein levels. The BDNF-associated downregulation of 5-HT(2A) receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT(2A) receptor levels in hippocampus confirming the association between 5-HT(2A) receptor and BDNF levels in vivo. In conclusion, our results point to a regulatory role of BDNF on 5-HT2A receptor levels. This interaction may be an important mechanism in the role of BDNF in affective disorders emphasizing the need for further elucidating the specificity and the mechanism behind this regulation.
U2 - 10.1016/j.neuint.2009.06.013
DO - 10.1016/j.neuint.2009.06.013
M3 - Journal article
C2 - 19563850
SN - 0197-0186
VL - 55
SP - 697
EP - 702
JO - Neurochemistry International
JF - Neurochemistry International
IS - 7
ER -