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PMID: 18718867 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus.

Molecular and cellular neurosciences ·Vol. 39 ·No. 3 ·2008-11-00 ·Pages 372-83

Chan JP, Cordeira J, Calderon GA, Iyer LK, Rios M

Abstract

Granule neurons generated in the adult mammalian hippocampus synaptically integrate to facilitate cognitive function and antidepressant efficacy. Here, we investigated the role of BDNF in facilitating their maturation in vivo. We found that depletion of central BDNF in mice elicited an increase in hippocampal cell proliferation without affecting cell survival or fate specification. However, new mutant neurons failed to fully mature as indicated by their lack of calbindin, reduced dendritic differentiation and an accumulation of calretinin(+) immature neurons in the BDNF mutant dentate gyrus. Furthermore, the facilitating effects of GABA(A) receptor stimulation on neurogenesis were absent in the mutants, suggesting that defects might be due to alterations in GABA signaling. Transcriptional analysis of the mutant hippocampal neurogenic region revealed increases in markers for immature neurons and decreases in neuronal differentiation facilitators. These findings demonstrate that BDNF is required for the terminal differentiation of new neurons in the adult hippocampus.

MeSH Terms
Animals Brain-Derived Neurotrophic Factor/genetics,metabolism Cell Differentiation/physiology Cell Movement Cell Proliferation Female Hippocampus/cytology Male Mice Mice, Inbred C57BL Mice, Knockout Neurons/cytology,physiology Receptor, trkB/metabolism Receptors, GABA-A/metabolism Stem Cells/cytology,physiology Transcription, Genetic gamma-Aminobutyric Acid/metabolism
Chemicals
Brain-Derived Neurotrophic Factor Receptors, GABA-A gamma-Aminobutyric Acid Receptor, trkB
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chan Jason P
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Cordeira Joshua
Calderon German A
Iyer Lakshmanan K
Rios Maribel
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Article Info
Journal
Molecular and cellular neurosciences
Abbr.
Mol Cell Neurosci
ISSN
1095-9327
DOI
10.1016/j.mcn.2008.07.017
Published
2008-11-00
Epub
2008-00-30
Pages
372-83
Language
English
Region
United States
NLM ID
9100095
PMCID
PMC2652348
Subset
IM
Grants
NIDDK NIH HHS · P30 DK34928 · United States
NIMH NIH HHS · R01 MH067817-05 · United States
NIDDK NIH HHS · P30 DK034928 · United States
NIMH NIH HHS · R01 MH067817 · United States
NIMH NIH HHS · R01 MH67817 · United States
NINDS NIH HHS · P30 NS047243 · United States
External Links
PubMed source DOI: 10.1016/j.mcn.2008.07.017 PMC Full Text View journal details
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