Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior

Chourbaji, S., Hellweg, R., Brandis, D., Zorner, B., Zacher, C., Lang, U. E., Henn, F. A., Hortnagl, H., Gass, P. (February 2004) Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior. Brain Res Mol Brain Res, 121 (1-2). pp. 28-36. ISSN 0169-328X (Print)0169-328X (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/14969734
DOI: 10.1016/j.molbrainres.2003.11.002

Abstract

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.

Item Type: Paper
Uncontrolled Keywords: Adrenocorticotropic Hormone/blood Analysis of Variance Animals Anxiety Biogenic Monoamines/ metabolism Brain/anatomy & histology/ enzymology/metabolism Brain Chemistry Brain-Derived Neurotrophic Factor/genetics/ metabolism Choline O-Acetyltransferase/ metabolism Chromatography, High Pressure Liquid/methods Conditioning, Classical/physiology Electrochemistry/methods Enzyme-Linked Immunosorbent Assay/methods Exploratory Behavior/physiology Fear/physiology Male Maze Learning/physiology Mice Mice, Inbred C57BL Mice, Knockout Motor Activity/physiology Nerve Growth Factor/analysis Psychomotor Performance/ physiology Reaction Time Stress, Physiological
Subjects: diseases & disorders
diseases & disorders > mental disorders
diseases & disorders > mental disorders > mood disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > animal behavior
organs, tissues, organelles, cell types and functions > organs types and functions > brain
diseases & disorders > mental disorders > mood disorders > depression
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date: 5 February 2004
Date Deposited: 04 Mar 2013 21:23
Last Modified: 04 Mar 2013 21:23
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27695

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