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Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice.
Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice.
- Source :
- European Journal of Neuroscience; Oct2003, Vol. 18 Issue 7, p1828-1836, 9p
- Publication Year :
- 2003
-
Abstract
- It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long-term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin-1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin-1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin-1 receptor knockout mice. Neurogenesis can be increased in wild-type but not neurokinin-1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain-derived neurotrophic factor are also two-fold higher in neurokinin-1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus-dependent learning and memory but found no clear enhancement in neurokinin-1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain-derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain-derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- TACHYKININS
DEVELOPMENTAL neurobiology
Subjects
Details
- Language :
- English
- ISSN :
- 0953816X
- Volume :
- 18
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- European Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 11169415
- Full Text :
- https://doi.org/10.1046/j.1460-9568.2003.02911.x