Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice

Journal of Neurochemistry - Tập 82 Số 6 - Trang 1367-1375 - 2002
Jaewon Lee1, Wenzhen Duan2, Mark P. Mattson3,4,2
1Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center Baltimore, Maryland 21224, USA.
2Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, Maryland, USA
3Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA
4Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Tóm tắt

AbstractTo determine the role of brain‐derived neurotrophic factor (BDNF) in the enhancement of hippocampal neurogenesis resulting from dietary restriction (DR), heterozygous BDNF knockout (BDNF +/–) mice and wild‐type mice were maintained for 3 months on DR or ad libitum (AL) diets. Mice were then injected with bromodeoxyuridine (BrdU) and killed either 1 day or 4 weeks later. Levels of BDNF protein in neurons throughout the hippocampus were decreased in BDNF +/– mice, but were increased by DR in wild‐type mice and to a lesser amount in BDNF +/– mice. One day after BrdU injection the number of BrdU‐labeled cells in the dentate gyrus of the hippocampus was significantly decreased in BDNF +/– mice maintained on the AL diet, suggesting that BDNF signaling is important for proliferation of neural stem cells. DR had no effect on the proliferation of neural stem cells in wild‐type or BDNF +/– mice. Four weeks after BrdU injection, numbers of surviving labeled cells were decreased in BDNF +/– mice maintained on either AL or DR diets. DR significantly improved survival of newly generated cells in wild‐type mice, and also improved their survival in BDNF +/– mice, albeit to a lesser extent. The majority of BrdU‐labeled cells in the dentate gyrus exhibited a neuronal phenotype at the 4‐week time point. The reduced neurogenesis in BDNF +/– mice was associated with a significant reduction in the volume of the dentate gyrus. These findings suggest that BDNF plays an important role in the regulation of the basal level of neurogenesis in dentate gyrus of adult mice, and that by promoting the survival of newly generated neurons BDNF contributes to the enhancement of neurogenesis induced by DR.

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Tài liệu tham khảo

10.1089/10430349950016393

10.1073/pnas.94.19.10432

10.1002/1531-8249(199901)45:1<8::AID-ART4>3.0.CO;2-V

10.1002/(SICI)1097-4695(199808)36:2<287::AID-NEU13>3.0.CO;2-B

10.1016/0006-8993(94)91857-0

10.1523/JNEUROSCI.17-07-02295.1997

10.1515/REVNEURO.1997.8.1.13

10.1038/375235a0

10.1006/exnr.1999.7225

10.1002/(SICI)1097-4547(19990715)57:2<195::AID-JNR5>3.0.CO;2-P

10.1385/JMN:16:1:1

10.1038/368147a0

10.1126/science.287.5457.1433

10.1093/geronj/38.1.36

10.1016/S0306-4522(97)00127-9

10.1111/j.1365-2818.1987.tb02837.x

10.1016/S0306-4522(00)00408-5

10.1006/exnr.2000.7415

10.1093/geronj/42.1.78

10.1016/S0306-4522(98)00112-2

Ip N. Y., 1993, Cultured hippocampal neurons show responses to BDNF, NT‐3, and NT‐4, but not NGF, J. Neurosci., 13, 3394, 10.1523/JNEUROSCI.13-08-03394.1993

10.1038/386493a0

10.1093/emboj/19.6.1290

10.1073/pnas.92.19.8856

10.1126/science.1067766

10.1006/exnr.1997.6434

10.1385/JMN:15:2:99

10.1038/77046

10.1046/j.0022-3042.2001.00747.x

Liebl D. J., 1997, Absence of sensory neurons before target innervation in brain‐derived neurotrophic factor‐, neurotrophin 3‐, and TrkC‐deficient embryonic mice, J. Neurosci., 17, 9113, 10.1523/JNEUROSCI.17-23-09113.1997

10.1111/j.1460-9568.1996.tb01607.x

10.1016/S0169-328X(99)00295-8

10.1016/S0165-0270(98)00100-9

10.1073/pnas.96.26.15239

10.1016/0014-4886(95)90002-0

10.1002/(SICI)1097-4695(19990615)39:4<569::AID-NEU10>3.0.CO;2-F

10.1016/S0306-4522(00)00428-0

10.1523/JNEUROSCI.17-10-03727.1997

10.1038/6368

10.1038/4151030a

10.1038/35066584

10.1016/S0304-3940(01)02331-X

10.1016/0197-4580(93)90112-O

10.1523/JNEUROSCI.22-05-01532.2002

10.1038/7449

10.1002/(SICI)1097-4547(19990915)57:6<830::AID-JNR8>3.0.CO;2-2

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Journal of Neurochemistry

Tập 82 Số 6

1367-1375

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