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Title: Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas. Author: Hellweg R, Zueger M, Fink K, Hörtnagl H, Gass P. Journal: Neurobiol Dis; 2007 Jan; 25(1):1-7. PubMed ID: 16990008. Abstract: The olfactory bulbectomy in rodents has been proposed as an animal model for depression. According to the neurotrophin and monoamine hypotheses of depression, the present study examined neurotrophin and monoamine (serotonin, norepinephrine, dopamine) levels in several depression-related brain regions of mice subjected to olfactory bulbectomy. As expected, bulbectomized animals revealed behavioral alterations such as locomotor hyperactivity and reduced gain of bodyweight, regarded as correlates of a depressive-like state. Compared to sham-operated animals, bulbectomized mice demonstrated significantly increased brain-derived neurotrophic factor (BDNF), but regular nerve growth factor (NGF), protein levels in hippocampus (+108%) and frontal cortex (+48%) 16 days after olfactory bulbectomy. In these brain regions as well as in the hypothalamus, bulbectomy also caused a reduction of the molar ratio of 5-hydroxyindoleacetic acid to serotonin (5-HT) indicating a decrease in 5-HT turnover. Similarly, a hypofunction of the dopamine (DA) turnover was evident only in the hypothalamus in response to olfactory bulbectomy, presenting a decrease in the ratio 3,4 dihydroxyphenylacetic acid/DA with increased levels of DA. In all other brain areas investigated the levels of DA, its metabolite DOPAC and norepinephrine remained unaltered. Thus, olfactory bulbectomy seems to be a valid animal model also in mice related to serotonergic dysfunctions resembling bulbectomized rats that are a well-known model of hyposerotoninergic agitated depression. With respect to the common BDNF hypothesis of depression--predicting decreased BDNF expression in depression-related brain areas--the novel and challenging conclusions concern the increased BDNF protein levels in target regions of the cholinergic basal forebrain system in bulbectomized mice.[Abstract] [Full Text] [Related] [New Search]