Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression.

TitleExploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression.
Publication TypeJournal Article
Year of Publication2004
AuthorsSzapacs, ME, Mathews TA, Tessarollo L, Ernest Lyons W, Mamounas LA, Andrews AM
JournalJournal of neuroscience methods
Volume140
Issue1-2
Pagination81-92
Date Published2004 Dec 30
ISSN0165-0270
KeywordsAging, Animals, Brain, Brain-Derived Neurotrophic Factor, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Extracellular Fluid, Female, Male, Membrane Glycoproteins, Membrane Transport Proteins, Mice, Mice, Knockout, microdialysis, mood disorders, Nerve Degeneration, Nerve Tissue Proteins, Neurochemistry, Serotonin, Serotonin Plasma Membrane Transport Proteins, Sex Characteristics, Synaptic Transmission, Up-Regulation
Abstract

Serotonin (5-HT) has been proposed to promote neuronal plasticity during the treatment of mood and anxiety disorders and following neurodegenerative insult by altering the expression of critical genes including brain-derived neurotrophic factor (BDNF). In this study, mice with constitutive reductions in the serotonin transporter (SERT) or BDNF were investigated to further assess the functional relationship between serotonin neurotransmission and BDNF expression. Using a modified extraction procedure and a commercial enzyme-linked immunosorbant assay, 50% decreases in BDNF protein in hippocampus, frontal cortex and brain stem were confirmed in 4-month-old mice lacking one copy of the BDNF gene (BDNF(+/-)). By contrast, 4-month-old male and female mice with partial (SERT(+/-)) or complete (SERT(-/-)) reductions in SERT expression showed no differences in BDNF protein levels compared to SERT(+/+) mice, although male SERT knockout mice of all genotypes had higher BDNF levels in hippocampus, frontal cortex, and brain stem than female animals. Microdialysis also was performed in BDNF(+/-) mice. In addition to other phenotypic aspects suggestive of altered serotonin neurotransmission, BDNF(+/-) mice show accelerated age-related degeneration of 5-HT forebrain innervation. Nevertheless, extracellular 5-HT levels determined by zero net flux microdialysis were similar between BDNF(+/+) and BDNF(+/-) mice in striatum and frontal cortex at 8-12 months of age. These data illustrate that a 50% decrease in BDNF does not appear to be sufficient to cause measurable changes in basal extracellular 5-HT concentrations and, furthermore, that constitutive reductions in SERT expression are not associated with altered BDNF protein levels at the ages and in the brain regions examined in this study.

DOI10.3791/1786
Alternate JournalJ. Neurosci. Methods