MPP+ decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons

Yuyang Sun, Senthil Selvaraj, Sumali Pandey, Kristen M. Humphrey, James D. Foster, Min Wu, John A. Watt, Brij B. Singh, Joyce E. Ohm

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Parkinson’s disease is a neurodegenerative disorder involving the progressive loss of dopaminergic neurons (DNs), with currently available therapeutics, such as L-Dopa, only able to relieve some symptoms. Stem cell replacement is an attractive therapeutic option for PD patients, and DNs derived by differentiating patient specific stem cells under defined in-vitro conditions may present a viable opportunity to replace dying neurons. We adopted a previously published approach to differentiate Mesenchymal Stem Cells (MSCs) into DN using a 12-day protocol involving FGF-2, bFGF, SHH ligand and BDNF. While MSC-derived DNs have been characterized for neuronal markers and electrophysiological properties, we investigated store-operated calcium entry (SOCE) mechanisms of these DNs under normal conditions, and upon exposure to environmental neurotoxin, 1-methyl, 4-phenyl pyridinium ion (MPP+). Overall, we show that MSC-derived DNs are functional with regard to SOCE mechanisms, and MPP+ exposure dysregulates calcium signaling, making them vulnerable to neurodegeneration. Since in-vitro differentiation of MSCs into DNs is an important vehicle for PD disease modeling and regenerative medicine, the results of this study may help with understanding of the pathological mechanisms underlying PD.

Original languageEnglish
Article number11715
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

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Dopaminergic Neurons
Mesenchymal Stromal Cells
Calcium
Stem Cells
1-Methyl-4-phenylpyridinium
Regenerative Medicine
Calcium Signaling
Brain-Derived Neurotrophic Factor
Environmental Exposure
Neurotoxins
Levodopa
Fibroblast Growth Factor 2
Neurodegenerative Diseases
Parkinson Disease
Ions
Ligands
Neurons
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

MPP+ decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons. / Sun, Yuyang; Selvaraj, Senthil; Pandey, Sumali; Humphrey, Kristen M.; Foster, James D.; Wu, Min; Watt, John A.; Singh, Brij B.; Ohm, Joyce E.

In: Scientific Reports, Vol. 8, No. 1, 11715, 01.12.2018.

Research output: Contribution to journalArticle

Sun, Yuyang ; Selvaraj, Senthil ; Pandey, Sumali ; Humphrey, Kristen M. ; Foster, James D. ; Wu, Min ; Watt, John A. ; Singh, Brij B. ; Ohm, Joyce E. / MPP+ decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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