PMID- 18322085
OWN - NLM
STAT- MEDLINE
DCOM- 20080407
LR  - 20220316
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 10
DP  - 2008 Mar 5
TI  - Variant brain-derived neurotrophic factor (Val66Met) alters adult olfactory bulb 
      neurogenesis and spontaneous olfactory discrimination.
PG  - 2383-93
LID - 10.1523/JNEUROSCI.4387-07.2008 [doi]
AB  - Neurogenesis, the division, migration, and differentiation of new neurons, occurs 
      throughout life. Brain derived neurotrophic factor (BDNF) has been identified as 
      a potential signaling molecule regulating neurogenesis in the subventricular zone 
      (SVZ), but its functional consequences in vivo have not been well defined. We 
      report marked and unexpected deficits in survival but not proliferation of newly 
      born cells of adult knock-in mice containing a variant form of BDNF [a valine 
      (Val) to methionine (Met) substitution at position 66 in the prodomain of BDNF 
      (Val66Met)], a genetic mutation shown to lead to a selective impairment in 
      activity-dependent BDNF secretion. Utilizing knock-out mouse lines, we identified 
      BDNF and tyrosine receptor kinase B (TrkB) as the critical molecules for the 
      observed impairments in neurogenesis, with p75 knock-out mice showing no effect 
      on cell proliferation or survival. We then localized the activated form of TrkB 
      to a discrete population of cells, type A migrating neuroblasts, and demonstrate 
      a decrease in TrkB phosphorylation in the SVZ of Val66Met mutant mice. With these 
      findings, we identify TrkB signaling, potentially through activity dependent 
      release of BDNF, as a critical step in the survival of migrating neuroblasts. 
      Utilizing a behavioral task shown to be sensitive to disruptions in olfactory 
      bulb neurogenesis, we identified specific impairments in spontaneous olfactory 
      discrimination, but not general olfactory sensitivity or habituation to olfactory 
      stimuli in BDNF mutant mice. Through these observations, we have identified novel 
      links between genetic variant BDNF and adult neurogenesis in vivo, which may 
      contribute to significant impairments in olfactory function.
FAU - Bath, Kevin G
AU  - Bath KG
AD  - Department of Psychiatry, Weill Medical College of Cornell University, New York, 
      New York 10065, USA. kgb2001@med.cornell.edu
FAU - Mandairon, Nathalie
AU  - Mandairon N
FAU - Jing, Deqiang
AU  - Jing D
FAU - Rajagopal, Rithwick
AU  - Rajagopal R
FAU - Kapoor, Ruchi
AU  - Kapoor R
FAU - Chen, Zhe-Yu
AU  - Chen ZY
FAU - Khan, Tanvir
AU  - Khan T
FAU - Proenca, Catia C
AU  - Proenca CC
FAU - Kraemer, Rosemary
AU  - Kraemer R
FAU - Cleland, Thomas A
AU  - Cleland TA
FAU - Hempstead, Barbara L
AU  - Hempstead BL
FAU - Chao, Moses V
AU  - Chao MV
FAU - Lee, Francis S
AU  - Lee FS
LA  - eng
GR  - P01 HD023315/HD/NICHD NIH HHS/United States
GR  - NS30687/NS/NINDS NIH HHS/United States
GR  - NS21072/NS/NINDS NIH HHS/United States
GR  - R01 NS052819-03/NS/NINDS NIH HHS/United States
GR  - R01 NS021072/NS/NINDS NIH HHS/United States
GR  - K08 MH068850-04/MH/NIMH NIH HHS/United States
GR  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - MH060478/MH/NIMH NIH HHS/United States
GR  - R01 NS030687/NS/NINDS NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
GR  - R25 MH060478/MH/NIMH NIH HHS/United States
GR  - R56 NS021072/NS/NINDS NIH HHS/United States
GR  - MH068850/MH/NIMH NIH HHS/United States
GR  - HD23315/HD/NICHD NIH HHS/United States
GR  - K08 MH068850/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/deficiency/*genetics/metabolism
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Cell Survival/genetics
MH  - Cells, Cultured
MH  - Discrimination Learning/*physiology
MH  - *Genetic Variation
MH  - Male
MH  - Methionine/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Olfactory Bulb/*cytology/*growth & development/physiology
MH  - Olfactory Pathways/*physiology
MH  - Protein Structure, Tertiary/genetics
MH  - Receptor, trkB/genetics
MH  - Stem Cells/physiology
MH  - Valine/genetics
PMC - PMC2679965
MID - NIHMS43608
EDAT- 2008/03/07 09:00
MHDA- 2008/04/09 09:00
PMCR- 2008/09/05
CRDT- 2008/03/07 09:00
PHST- 2008/03/07 09:00 [pubmed]
PHST- 2008/04/09 09:00 [medline]
PHST- 2008/03/07 09:00 [entrez]
PHST- 2008/09/05 00:00 [pmc-release]
AID - 28/10/2383 [pii]
AID - 3323936 [pii]
AID - 10.1523/JNEUROSCI.4387-07.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Mar 5;28(10):2383-93. doi: 10.1523/JNEUROSCI.4387-07.2008.