PMID- 28939435
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20180920
IS  - 0925-4439 (Print)
IS  - 0925-4439 (Linking)
VI  - 1864
IP  - 1
DP  - 2018 Jan
TI  - Characterization of subventricular zone-derived progenitor cells from mild and 
      late symptomatic YAC128 mouse model of Huntington's disease.
PG  - 34-44
LID - S0925-4439(17)30324-1 [pii]
LID - 10.1016/j.bbadis.2017.09.009 [doi]
AB  - Huntington's disease (HD) is caused by an expansion of CAG repeats in the HTT 
      gene, leading to expression of mutant huntingtin (mHTT) and selective striatal 
      neuronal loss, frequently associated with mitochondrial dysfunction and decreased 
      support of brain-derived neurotrophic factor (BDNF). New neurons derived from the 
      subventricular zone (SVZ) are apparently not able to rescue HD pathological 
      features. Thus, we analyzed proliferation, migration and differentiation of adult 
      SVZ-derived neural stem/progenitor cells (NSPC) from mild (6month-old (mo)) and 
      late (10mo) symptomatic HD YAC128 mice expressing full-length (FL)-mHTT versus 
      age-matched wild-type (WT) mice. SVZ cells derived from 6mo YAC128 mice exhibited 
      higher migratory capacity and a higher number of MAP2+ and synaptophysin+cells, 
      compared to WT cells; MAP2 labeling was enhanced after exposure to BDNF. However, 
      BDNF-evoked neuronal differentiation was not observed in 10mo YAC128 SVZ-derived 
      cells. Interestingly, 6mo YAC128 SVZ-derived cells showed increased intracellular 
      Ca(2+) levels in response to KCl, which was potentiated by BDNF, evidencing the 
      presence of differentiated neurons. In contrast, KCl depolarization-induced 
      intracellular Ca(2+) increase in 10mo YAC128 SVZ-derived cells was shown to be 
      increased only in BDNF-treated YAC128 SVZ-derived cells, suggestive of decreased 
      differentiation capacity. In addition, BDNF-untreated NSPC from 10mo YAC128 mice 
      exhibited lower mitochondrial membrane potential and increased mitochondrial 
      Ca(2+) accumulation, in relation with NSPC from 6mo YAC128 mice. Data evidence 
      age-dependent reduced migration and decreased acquisition of a neuronal 
      phenotype, accompanied by decreased mitochondrial membrane potential in 
      SVZ-derived cells from YAC128 mice through HD symptomatic phases.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Silva, Ana C
AU  - Silva AC
AD  - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 
      Coimbra, Portugal.
FAU - Ferreira, Ildete L
AU  - Ferreira IL
AD  - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 
      Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University 
      of Coimbra, Portugal.
FAU - Hayden, Michael R
AU  - Hayden MR
AD  - Centre for Molecular Medicine and Therapeutics, Child and Family Research 
      Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
FAU - Ferreiro, Elisabete
AU  - Ferreiro E
AD  - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 
      Coimbra, Portugal; Institute for Interdisciplinary Research (IIIUC), University 
      of Coimbra, Portugal.
FAU - Rego, A Cristina
AU  - Rego AC
AD  - CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 
      Coimbra, Portugal; FMUC-Faculty of Medicine, University of Coimbra, 3000-548 
      Coimbra, Portugal. Electronic address: acrego@cnc.uc.pt.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170920
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Htt protein, mouse)
RN  - 0 (Huntingtin Protein)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - Huntingtin Protein/genetics
MH  - Huntington Disease/genetics/*pathology
MH  - Lateral Ventricles/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Neural Stem Cells/*pathology
MH  - Severity of Illness Index
OTO - NOTNLM
OT  - BDNF
OT  - Calcium handling
OT  - Mitochondrial membrane potential
OT  - Mutant huntingtin
OT  - Neurospheres
OT  - Subventricular zone
OT  - YAC128 mice
EDAT- 2017/09/25 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/09/24 06:00
PHST- 2017/02/06 00:00 [received]
PHST- 2017/09/02 00:00 [revised]
PHST- 2017/09/12 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
AID - S0925-4439(17)30324-1 [pii]
AID - 10.1016/j.bbadis.2017.09.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):34-44. doi: 
      10.1016/j.bbadis.2017.09.009. Epub 2017 Sep 20.