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BDNF downregulates 5-HT2A receptor protein levels in hippocampal cultures

Trajkovska, V. ; Santini, M. A. ; Marcussen, A. B. ; Thomsen, M. S. ; Hansen, H. H. ; Mikkelsen, J. D. ; Arneberg, L. ; Kokaia, Merab LU ; Knudsen, G. M. and Aznar, S. (2009) In Neurochemistry International 55(7). p.697-702
Abstract
Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT2A) have been related to depression pathology. Specific 5-HT2A receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT2A receptor level. Here we show a direct effect of BDNF on 5-HT2A 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-HT2A receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50 ng/mL BDNF resulted in downregulation of 5-HT2A, but not of 5-HT1A, receptor protein... (More)
Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT2A) have been related to depression pathology. Specific 5-HT2A receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT2A receptor level. Here we show a direct effect of BDNF on 5-HT2A 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-HT2A receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50 ng/mL BDNF resulted in downregulation of 5-HT2A, but not of 5-HT1A, receptor protein levels. The BDNF-associated downregulation of 5-HT2A receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT2A receptor levels in hippocampus confirming the association between 5-HT2A 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. (C) 2009 Elsevier Ltd. All rights reserved. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hippocampus, Mature organotypic cultures, Serotonin, Neurotrophins, Depression, Neuronal cultures
in
Neurochemistry International
volume
55
issue
7
pages
697 - 702
publisher
Elsevier
external identifiers
  • wos:000270492000034
  • scopus:69349085056
  • pmid:19563850
ISSN
0197-0186
DOI
10.1016/j.neuint.2009.06.013
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Restorative Neurology (0131000160)
id
1fdd16d8-cade-46c6-b3bf-0719173f035c (old id 1489469)
date added to LUP
2016-04-01 12:37:22
date last changed
2022-02-19 01:00:08
@article{1fdd16d8-cade-46c6-b3bf-0719173f035c,
  abstract     = {{Both brain-derived neurotrophic factor (BDNF) and the serotonin receptor 2A (5-HT2A) have been related to depression pathology. Specific 5-HT2A receptor changes seen in BDNF conditional mutant mice suggest that BDNF regulates the 5-HT2A receptor level. Here we show a direct effect of BDNF on 5-HT2A 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-HT2A receptor levels were further corroborated in (BDNF +/-) mice with reduced BDNF levels. In primary neuronal cultures, 7 days exposure to 25 and 50 ng/mL BDNF resulted in downregulation of 5-HT2A, but not of 5-HT1A, receptor protein levels. The BDNF-associated downregulation of 5-HT2A receptor levels was also observed in mature hippocampal organotypic cultures, excluding confounding effects of BDNF on immature tissue. BDNF +/- mice showed significant increased 5-HT2A receptor levels in hippocampus confirming the association between 5-HT2A 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. (C) 2009 Elsevier Ltd. All rights reserved.}},
  author       = {{Trajkovska, V. and Santini, M. A. and Marcussen, A. B. and Thomsen, M. S. and Hansen, H. H. and Mikkelsen, J. D. and Arneberg, L. and Kokaia, Merab and Knudsen, G. M. and Aznar, S.}},
  issn         = {{0197-0186}},
  keywords     = {{Hippocampus; Mature organotypic cultures; Serotonin; Neurotrophins; Depression; Neuronal cultures}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{697--702}},
  publisher    = {{Elsevier}},
  series       = {{Neurochemistry International}},
  title        = {{BDNF downregulates 5-HT2A receptor protein levels in hippocampal cultures}},
  url          = {{http://dx.doi.org/10.1016/j.neuint.2009.06.013}},
  doi          = {{10.1016/j.neuint.2009.06.013}},
  volume       = {{55}},
  year         = {{2009}},
}