PMID- 22252710
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20120307
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 90
IP  - 5
DP  - 2012 May
TI  - Sendai virus vector-mediated brain-derived neurotrophic factor expression 
      ameliorates memory deficits and synaptic degeneration in a transgenic mouse model 
      of Alzheimer's disease.
PG  - 981-9
LID - 10.1002/jnr.22830 [doi]
AB  - Growing evidence suggests that decreased brain-derived neurotrophic factor (BDNF) 
      levels are associated with Alzheimer's disease (AD) pathogenesis. Therefore, BDNF 
      gene therapy is considered to be a promising therapeutic strategy for treating 
      AD. Sendai virus (SeV) is a type I parainfluenza virus that does not interact 
      with host chromosomes because of its strict cytoplasmic life cycle. Although SeV 
      is nonpathogenic in primates, including humans, its infectivity for neurons is 
      strong. Here we demonstrate that SeV vectors effectively infected neurons, even 
      though they were injected into subcortical white matter. Moreover, SeV vectors 
      significantly induced BDNF expression, ameliorating synaptic degeneration and 
      memory deficits in a transgenic mouse model of AD (Tg2576). This is the first 
      study to demonstrate that viral vector administration in white matter is 
      sufficient to restore cognitive function in vivo. These results also support the 
      feasibility of using SeV vectors for gene therapy targeting the brain.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Iwasaki, Yuki
AU  - Iwasaki Y
AD  - Laboratory of Disease Control, Tsukuba Primate Research Center, National 
      Institute of Biomedical Innovation, Ibaraki, Japan.
FAU - Negishi, Takayuki
AU  - Negishi T
FAU - Inoue, Makoto
AU  - Inoue M
FAU - Tashiro, Tomoko
AU  - Tashiro T
FAU - Tabira, Takeshi
AU  - Tabira T
FAU - Kimura, Nobuyuki
AU  - Kimura N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120118
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
SB  - IM
MH  - Alzheimer Disease/*complications/genetics
MH  - Amyloid beta-Peptides/pharmacology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/pharmacology/*therapeutic use
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Hippocampus/pathology
MH  - Humans
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - *Memory Disorders/etiology/pathology/therapy
MH  - Mice
MH  - Mice, Transgenic
MH  - *Nerve Degeneration/etiology/pathology/therapy
MH  - Neurons/drug effects
MH  - Peptide Fragments/pharmacology
MH  - Sendai virus/genetics/*physiology
MH  - Synapses/drug effects/*metabolism/pathology
EDAT- 2012/01/19 06:00
MHDA- 2012/07/17 06:00
CRDT- 2012/01/19 06:00
PHST- 2011/08/09 00:00 [received]
PHST- 2011/10/18 00:00 [revised]
PHST- 2011/10/21 00:00 [accepted]
PHST- 2012/01/19 06:00 [entrez]
PHST- 2012/01/19 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - 10.1002/jnr.22830 [doi]
PST - ppublish
SO  - J Neurosci Res. 2012 May;90(5):981-9. doi: 10.1002/jnr.22830. Epub 2012 Jan 18.