PMID- 31250384
OWN - NLM
STAT- MEDLINE
DCOM- 20200402
LR  - 20210110
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 12
DP  - 2019 Dec
TI  - Neurotrophic Factors Mediated Activation of Astrocytes Ameliorate Memory Loss by 
      Amyloid Clearance after Transplantation of Lineage Negative Stem Cells.
PG  - 8420-8434
LID - 10.1007/s12035-019-01680-z [doi]
AB  - Alzheimer's disease (AD) is one of the untreatable neurodegenerative disorders 
      with associated societal burden. Current therapies only provide symptomatic 
      relief without altering the rate of disease progression as reported by Lanctot et 
      al. (Therapeutic Advances in Neurological Disorders 2 (3):163-180, 2009). The 
      increased number of failed clinical trials in last two decades indicates the 
      imperative need to explore alternative therapies for AD as reported by Tuszynski 
      et al. (Nature Medicine 11 (5):551-555, 2005) and Liyanage et al. (Alzheimer's & 
      Dementia 4:628-635, 2005). In this study, we aimed to decipher the role of 
      neurotrophic factors in the reversal of memory loss by transplantation of lineage 
      negative (Lin-ve) stem cells in a male mouse model of cognitive impairment 
      induced by intrahippocampal injection of amyloid beta-42 (Abeta-42). The efficacy of 
      human umbilical cord blood (hUCB) derived Lin-ve stem cells were analyzed by 
      neurobehavioral parameters, i.e., Morris water maze and passive avoidance after 
      bilateral intra-hippocampal transplantation using stereotaxic surgery. Real-time 
      PCR and immunohistochemistry was carried out in brain tissues in order to analyze 
      the expression of neurotrophic factors, apoptotic, astrocytic, and other neuronal 
      cell markers. The transplantation of Lin-ve stem cells led to reversal of memory 
      loss associated with reduction of Abeta-42 deposition from the brains. The molecular 
      analysis revealed increase in neurotrophic factors, i.e., glial derived 
      neurotrophic factor (GDNF), ciliary derived neurotrophic factor (CNTF), and 
      Brain-derived neurotrophic factor (BDNF) after transplantation. The 
      administration of ANA-12, a TrkB inhibitor, reversed the behavioral and molecular 
      effects of stem cell transplantation suggesting involvement of BDNF-TrkB pathway 
      in the rescue of memory loss. We believe that the amyloid clearance results from 
      activation of astrocytes and anti-apoptotic pathways added by neurotrophic 
      factors.
FAU - Bali, P
AU  - Bali P
AD  - Department of Biophysics, Panjab University, Chandigarh, 160014, India.
AD  - Neuroscience Research Lab, Department of Neurology, Post Graduated Institute of 
      Medical Education and Research, Chandigarh, 160012, India.
FAU - Banik, A
AU  - Banik A
AD  - Department of Pharmacology and Chemical Biology, Emory University School of 
      Medicine, Rollins Research Center, Atlanta, GA, 30322, USA.
FAU - Nehru, B
AU  - Nehru B
AD  - Department of Biophysics, Panjab University, Chandigarh, 160014, India.
FAU - Anand, Akshay
AU  - Anand A
AUID- ORCID: 0000-0001-9003-3532
AD  - Neuroscience Research Lab, Department of Neurology, Post Graduated Institute of 
      Medical Education and Research, Chandigarh, 160012, India. 
      akshay1anand@rediffmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190627
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Amyloid)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Nerve Growth Factors)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Amyloid/*metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Astrocytes/metabolism/*pathology
MH  - Behavior, Animal
MH  - Brain/pathology
MH  - *Cell Lineage
MH  - Cell Proliferation
MH  - Conditioning, Classical
MH  - Fear
MH  - Fetal Blood/cytology
MH  - Humans
MH  - Male
MH  - Maze Learning
MH  - Memory Disorders/*therapy
MH  - Mice
MH  - Models, Biological
MH  - Nerve Growth Factors/metabolism
MH  - Receptor, trkB/metabolism
MH  - *Stem Cell Transplantation
MH  - Stem Cells/*cytology/metabolism
MH  - Swimming
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid injury
OT  - BDNF
OT  - Lineage negative stem cells
OT  - Memory loss
OT  - Neurotrophic factor
OT  - Umbilical cord blood
EDAT- 2019/06/30 06:00
MHDA- 2020/04/03 06:00
CRDT- 2019/06/29 06:00
PHST- 2019/03/02 00:00 [received]
PHST- 2019/06/14 00:00 [accepted]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/04/03 06:00 [medline]
PHST- 2019/06/29 06:00 [entrez]
AID - 10.1007/s12035-019-01680-z [pii]
AID - 10.1007/s12035-019-01680-z [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Dec;56(12):8420-8434. doi: 10.1007/s12035-019-01680-z. Epub 
      2019 Jun 27.