Research article summary (published 20 Sep 2006):

Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies.

Full Abstract

1. Brain-derived neurotrophic factor (BDNF) supports serotonergic neuronal development and our recent study found that heterozygous mice lacking one BDNF gene allele interbred with male serotonin transporter (SERT) knockout mice had greater reductions in brain tissue serotonin concentrations, greater increases in anxiety-like behaviors and greater ACTH responses to stress than found in the SERT knockout mice alone. 2. We investigated here whether there might be gender differences in these consequences of combined SERT and BDNF deficiencies by extending the original studies to female mice, and also to an examination of the effects of ovariectomy and tamoxifen in these female mice, and of 21-day 17-beta estradiol implantation to male mice. 3. We found that unlike the male SERTxBDNF-deficient mice, female SERTxBDNF mice appeared protected by their gender in having significantly lesser reductions in serotonin concentrations in hypothalamus and other brain regions than males, relative to controls. Likewise, in the elevated plus maze, female SERTxBDNF-deficient mice demonstrated no increases in the anxiety-like behaviors previously found in males. 4. Furthermore, female SERTxBDNF mice did not manifest the approximately 40% reduction in the expression of TrkB receptors or the approximately 30% reductions in dopamine and its metabolites that male SERTxBDNF did. After estradiol implantation in male SERTxBDNF mice, hypothalamic serotonin was significantly increased compared to vehicle-implanted mice. These findings support the hypothesis that estrogen may enhance BDNF function via its TrkB receptor, leading to alterations in the serotonin circuits, which modulate anxiety-like behaviors. 5. This double-mutant mouse model contributes to the knowledge base that will help in understanding genexgenexgender interactions in studies of SERT and BDNF gene polymorphisms in human genetic diseases such as anxiety disorders and depression.

Author information

Author/s: Ren-Patterson, Renee F (RF); Cochran, Lauren W (LW); Holmes, Andrew (A); Lesch, Klaus-Peter (KP); Lu, Bai (B); Murphy, Dennis L (DL);

Affiliation: Laboratory of Clinical Science, NIMH, Bethesda, MD 20892-1264, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural

Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol), published in United States. (Language: eng)

Reference: -2006 Jul-Aug; vol 26 (issue 4-6) : pp 755-80

Dates: Created 2006/10/09; Completed 2007/04/24;

PMID: 17029036, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Anxiety - genetics; metabolism Behavior, Animal Biogenic Monoamines - metabolism Brain - drug effects; metabolism Brain-Derived Neurotrophic Factor - genetics Crosses, Genetic Estradiol - pharmacology

Estradiol - pharmacology Female Male Mice Mice, Knockout Receptor, trkB - metabolism Serotonin Plasma Membrane Transport Proteins - genetics Sex Characteristics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Biogenic Monoamines (0) ; Brain-Derived Neurotrophic Factor (0) ; Serotonin Plasma Membrane Transport Proteins (0) ; Slc6a4 protein, mouse (0) ; Estradiol (50-28-2) ; Receptor, trkB (EC 2.7.1.112)

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