PMID- 36228967
OWN - NLM
STAT- MEDLINE
DCOM- 20221130
LR  - 20221229
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 123
DP  - 2022 Dec
TI  - BDNF-modified human umbilical cord mesenchymal stem cells-derived 
      dopaminergic-like neurons improve rotation behavior of Parkinson's disease rats 
      through neuroprotection and anti-neuroinflammation.
PG  - 103784
LID - S1044-7431(22)00090-2 [pii]
LID - 10.1016/j.mcn.2022.103784 [doi]
AB  - Parkinson's disease (PD) is a neurodegenerative disease still without any cure. 
      Brain-derived neurotrophic factor (BDNF) has shown therapeutic potential in PD, 
      which is limited by its short half-life and inability to penetrate the 
      blood-brain barrier. Stem cells not only present migration, differentiation and 
      neurotrophy characteristics, but also can be used as delivery vectors for BDNF. 
      This study aimed to investigate the therapeutic effects and possible mechanisms 
      of BDNF-modified human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived 
      dopaminergic (DAergic)-like neurons in the PD rats. Results showed that 
      transplantation of BDNF-modified hUC-MSCs-derived DAergic-like neurons improved 
      the apomorphine induced rotation behavior of PD rats, increased the dopamine 
      concentration and the expression of glial fibrillary acidic protein (GFAP) and 
      ionized calcium-binding adaptor molecule-1 (Iba-1) in the striatum, promoted the 
      expression of tyrosine hydroxylase (TH), nuclear receptor-related factor 1 
      (Nurr1), pituitary homeobox 3 (Pitx3), BDNF, tyrosine kinase B (TrkB), 
      phosphatidylinositol-3-hydroxykinase (PI3K), phosphorylated protein kinase B 
      (p-Akt), heat shock protein 60 (Hsp60), toll-like receptor 4 (TLR4) and myeloid 
      differentiation factor 88 (MyD88) and inhibited the neural apoptosis in the 
      substantia nigra (SN) and striatum. Results suggest that BDNF-modified 
      hUC-MSCs-derived DAergic-like neurons improve the rotation of PD rats might 
      through neuroprotection and anti-neuroinflammation by regulating the 
      BDNF-TrkB-PI3K/Akt and Hsp60-TLR4/MyD88 signaling pathways, respectively.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Jiang, Zhi
AU  - Jiang Z
AD  - Department of Geriatrics, The Second Affiliated Hospital, Key Laboratory for 
      Aging & Disease, Nanjing Medical University, Nanjing 210011, China; Department of 
      Neurology, The Second People's Hospital of NanTong, Nantong 226006, China.
FAU - Wang, Jie
AU  - Wang J
AD  - Department of Geriatrics, The Second Affiliated Hospital, Key Laboratory for 
      Aging & Disease, Nanjing Medical University, Nanjing 210011, China; Department of 
      Neurology, The Affiliated Jiangning Hospital of Nanjing Medical University, 
      Nanjing 211100, China.
FAU - Sun, Gaohui
AU  - Sun G
AD  - Department of Geriatrics, The Second Affiliated Hospital, Key Laboratory for 
      Aging & Disease, Nanjing Medical University, Nanjing 210011, China.
FAU - Feng, Meijiang
AU  - Feng M
AD  - Department of Geriatrics, The Second Affiliated Hospital, Key Laboratory for 
      Aging & Disease, Nanjing Medical University, Nanjing 210011, China. Electronic 
      address: mjfeng416@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221011
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - VTD58H1Z2X (Dopamine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - *Parkinson Disease/therapy/metabolism
MH  - Dopamine/metabolism
MH  - *Mesenchymal Stem Cell Transplantation/methods
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Neuroprotection
MH  - *Neurodegenerative Diseases/metabolism
MH  - Myeloid Differentiation Factor 88/metabolism/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Rats, Sprague-Dawley
MH  - *Mesenchymal Stem Cells
MH  - Neurons/metabolism
MH  - Umbilical Cord/metabolism
MH  - Dopaminergic Neurons/metabolism
OTO - NOTNLM
OT  - Anti-neuroinflammation
OT  - Brain-derived neurotrophic factor
OT  - Dopaminergic-like neurons
OT  - Human umbilical cord mesenchymal stem cells
OT  - Neuroprotection
OT  - Parkinson's disease
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/10/14 06:00
MHDA- 2022/12/01 06:00
CRDT- 2022/10/13 19:37
PHST- 2022/08/11 00:00 [received]
PHST- 2022/10/04 00:00 [revised]
PHST- 2022/10/07 00:00 [accepted]
PHST- 2022/10/14 06:00 [pubmed]
PHST- 2022/12/01 06:00 [medline]
PHST- 2022/10/13 19:37 [entrez]
AID - S1044-7431(22)00090-2 [pii]
AID - 10.1016/j.mcn.2022.103784 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2022 Dec;123:103784. doi: 10.1016/j.mcn.2022.103784. Epub 2022 
      Oct 11.