PMID- 11517261
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20240420
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 17
DP  - 2001 Sep 1
TI  - Adenoviral brain-derived neurotrophic factor induces both neostriatal and 
      olfactory neuronal recruitment from endogenous progenitor cells in the adult 
      forebrain.
PG  - 6718-31
AB  - Neural progenitor cells persist throughout the adult forebrain subependyma, and 
      neurons generated from them respond to brain-derived neurotrophic factor (BDNF) 
      with enhanced maturation and survival. To induce neurogenesis from endogenous 
      progenitors, we overexpressed BDNF in the adult ventricular zone by transducing 
      the forebrain ependyma to constitutively express BDNF. We constructed a 
      bicistronic adenovirus bearing BDNF under cytomegalovirus (CMV) control, and 
      humanized green fluorescent protein (hGFP) under internal ribosomal entry site 
      (IRES) control. This AdCMV:BDNF:IRES:hGFP (AdBDNF) was injected into the lateral 
      ventricles of adult rats, who were treated for 18 d thereafter with the mitotic 
      marker bromodeoxyuridine (BrdU). Three weeks after injection, BDNF averaged 1 
      microg/gm in the CSF of AdBDNF-injected animals but was undetectable in control 
      CSF. In situ hybridization demonstrated BDNF and GFP mRNA expression restricted 
      to the ventricular wall. In AdBDNF-injected rats, the olfactory bulb exhibited a 
      >2.4-fold increase in the number of BrdU(+)-betaIII-tubulin(+) neurons, confirmed 
      by confocal imaging, relative to AdNull (AdCMV:hGFP) controls. Importantly, 
      AdBDNF-associated neuronal recruitment to the neostriatum was also noted, with 
      the treatment-induced addition of BrdU(+)-NeuN(+)-betaIII-tubulin(+) neurons to 
      the caudate putamen. Many of these cells also expressed glutamic acid 
      decarboxylase, cabindin-D28, and DARPP-32 (dopamine and cAMP-regulated 
      phosphoprotein of 32 kDa), markers of medium spiny neurons of the neostriatum. 
      These newly generated neurons survived at least 5-8 weeks after viral induction. 
      Thus, a single injection of adenoviral BDNF substantially augmented the 
      recruitment of new neurons into both neurogenic and non-neurogenic sites in the 
      adult rat brain. The intraventricular delivery of, and ependymal infection by, 
      viral vectors encoding neurotrophic agents may be a feasible strategy for 
      inducing neurogenesis from resident progenitor cells in the adult brain.
FAU - Benraiss, A
AU  - Benraiss A
AD  - Department of Neurology and Neuroscience, Cornell University Medical College, New 
      York, New York 10021, USA.
FAU - Chmielnicki, E
AU  - Chmielnicki E
FAU - Lerner, K
AU  - Lerner K
FAU - Roh, D
AU  - Roh D
FAU - Goldman, S A
AU  - Goldman SA
LA  - eng
GR  - R01 NS029813/NS/NINDS NIH HHS/United States
GR  - P50HL59312/HL/NHLBI NIH HHS/United States
GR  - R01 NS033106/NS/NINDS NIH HHS/United States
GR  - R01NS33106/NS/NINDS NIH HHS/United States
GR  - P50 HL059312/HL/NHLBI NIH HHS/United States
GR  - R01NS29813/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
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  - 0 (Luminescent Proteins)
RN  - 0 (RNA, Messenger)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage/biosynthesis/genetics
MH  - Bromodeoxyuridine
MH  - Cell Count
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cerebrospinal Fluid/metabolism
MH  - Genes, Reporter
MH  - Genetic Vectors/administration & dosage/genetics/metabolism
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Injections, Intraventricular
MH  - Luminescent Proteins/biosynthesis/genetics
MH  - Neostriatum/cytology/*drug effects/metabolism
MH  - Neurons/cytology/drug effects/metabolism
MH  - Olfactory Bulb/cytology/*drug effects/metabolism
MH  - Prosencephalon/cytology/*drug effects/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/cytology/*drug effects/metabolism
MH  - Tissue Distribution
PMC - PMC6763117
EDAT- 2001/08/23 10:00
MHDA- 2001/09/21 10:01
PMCR- 2002/03/01
CRDT- 2001/08/23 10:00
PHST- 2001/08/23 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/08/23 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - 21/17/6718 [pii]
AID - 5551 [pii]
AID - 10.1523/JNEUROSCI.21-17-06718.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Sep 1;21(17):6718-31. doi: 10.1523/JNEUROSCI.21-17-06718.2001.