PMID- 28283027
OWN - NLM
STAT- MEDLINE
DCOM- 20171025
LR  - 20220408
IS  - 2051-5960 (Electronic)
IS  - 2051-5960 (Linking)
VI  - 5
IP  - 1
DP  - 2017 Mar 10
TI  - Integrated analysis of genetic, behavioral, and biochemical data implicates 
      neural stem cell-induced changes in immunity, neurotransmission and mitochondrial 
      function in Dementia with Lewy Body mice.
PG  - 21
LID - 10.1186/s40478-017-0421-0 [doi]
LID - 21
AB  - We previously demonstrated that transplantation of murine neural stem cells 
      (NSCs) can improve motor and cognitive function in a transgenic model of Dementia 
      with Lewy Bodies (DLB). These benefits occurred without changes in human 
      alpha-synuclein pathology and were mediated in part by stem cell-induced elevation of 
      brain-derived neurotrophic factor (BDNF). However, instrastriatal NSC 
      transplantation likely alters the brain microenvironment via multiple mechanisms 
      that may synergize to promote cognitive and motor recovery. The underlying 
      neurobiology that mediates such restoration no doubt involves numerous genes 
      acting in concert to modulate signaling within and between host brain cells and 
      transplanted NSCs. In order to identify functionally connected gene networks and 
      additional mechanisms that may contribute to stem cell-induced benefits, we 
      performed weighted gene co-expression network analysis (WGCNA) on striatal tissue 
      isolated from NSC- and vehicle-injected wild-type and DLB mice. Combining 
      continuous behavioral and biochemical data with genome wide expression via 
      network analysis proved to be a powerful approach; revealing significant 
      alterations in immune response, neurotransmission, and mitochondria function. 
      Taken together, these data shed further light on the gene network and biological 
      processes that underlie the therapeutic effects of NSC transplantation on 
      alpha-synuclein induced cognitive and motor impairments, thereby highlighting 
      additional therapeutic targets for synucleinopathies.
FAU - Lakatos, Anita
AU  - Lakatos A
AD  - Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 
      USA.
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California, Irvine, USA.
FAU - Goldberg, Natalie R S
AU  - Goldberg NR
AD  - Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 
      USA.
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California, Irvine, USA.
FAU - Blurton-Jones, Mathew
AU  - Blurton-Jones M
AUID- ORCID: 0000-0002-7770-7157
AD  - Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 
      USA. mblurton@uci.edu.
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California, Irvine, USA. mblurton@uci.edu.
AD  - Department of Neurobiology & Behavior, University of California, Irvine, USA. 
      mblurton@uci.edu.
LA  - eng
GR  - K01 AG029378/AG/NIA NIH HHS/United States
GR  - P50 AG016573/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20170310
PL  - England
TA  - Acta Neuropathol Commun
JT  - Acta neuropathologica communications
JID - 101610673
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Cell Movement/genetics/physiology
MH  - Corpus Striatum/*metabolism
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Lewy Body Disease/genetics/*metabolism/psychology
MH  - Lysosomes/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Mitochondria/genetics/*metabolism
MH  - Neural Stem Cells/*metabolism
MH  - Neuroimmunomodulation/genetics/physiology
MH  - Phenotype
MH  - Recovery of Function/genetics/physiology
MH  - *Stem Cell Transplantation
MH  - Synaptic Transmission/genetics/*physiology
MH  - alpha-Synuclein/genetics/metabolism
PMC - PMC5345195
OTO - NOTNLM
OT  - Autophagy
OT  - Dopamine
OT  - Genomics
OT  - Glutamate
OT  - Lysosome
OT  - Memory
OT  - Neural stem cells
OT  - Synuclein
OT  - Transplantation
EDAT- 2017/03/12 06:00
MHDA- 2017/10/27 06:00
PMCR- 2017/03/10
CRDT- 2017/03/12 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/02/24 00:00 [accepted]
PHST- 2017/03/12 06:00 [entrez]
PHST- 2017/03/12 06:00 [pubmed]
PHST- 2017/10/27 06:00 [medline]
PHST- 2017/03/10 00:00 [pmc-release]
AID - 10.1186/s40478-017-0421-0 [pii]
AID - 421 [pii]
AID - 10.1186/s40478-017-0421-0 [doi]
PST - epublish
SO  - Acta Neuropathol Commun. 2017 Mar 10;5(1):21. doi: 10.1186/s40478-017-0421-0.