Early Expression of Neuronal Dopaminergic Markers in a Parkinson's Disease Model in Rats Implanted with Enteric Stem Cells (ENSCs)

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BACKGROUND: Parkinson's Disease (PD) is a common neurodegenerative disorder affecting the dopaminergic (DAergic) system. Replacement therapy is a promising alternative aimed at reconstructing the cytoarchitecture of affected brain regions in PD. Experimental approaches, such as the replacement of DAergic neurons with cells obtained from the Enteric Nervous System (ENS) has yet to be explored.

OBJECTIVE: To establish and characterize a cell replacement strategy with ENS Cells (ENSCs) in a PD model in rats.

METHODS: Since ENSCs can develop mature DAergic phenotypes, here we cultured undifferentiated cells from the myenteric plexus of newborn rats, establishing that they exhibit multipotential characteristics. These cells were characterized and further implanted in the Substantia nigra pars compacta (SNpc) of adult rats previously lesioned by a retrograde degenerative model produced by intrastriatal injection of 6-Hydroxydopamine (6-OHDA). DAergic markers were assessed in implants to validate their viability and possible differentiation once implanted.

RESULTS: Cell cultures were viable, exhibited stem cell features and remained partially undifferentiated until the time of implant. The retrograde lesion induced by 6-OHDA produced DAergic denervation, reducing the number of fibers and cells in the SNpc. Implantation of ENSCs in the SNpc of 6-OHDAlesioned rats was tracked after 5 and 10 days post-implant. During that time, the implant increased selective neuronal and DAergic markers, Including Microtubule-Associated Protein 2 (MAP-2), Dopamine Transporter (DAT), and Tyrosine Hydroxylase (TH).

CONCLUSION: Our novel results suggest that ENSCs possess a differentiating, proliferative and restorative potential that may offer therapeutic modalities to attenuate neurodegenerative events with the inherent demise of DAergic neurons.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

CNS & neurological disorders drug targets - 19(2020), 2 vom: 01., Seite 148-162

Sprache:

Englisch

Beteiligte Personen:

Parra-Cid, Carmen [VerfasserIn]
Orozco-Castillo, Eduardo [VerfasserIn]
García-López, Julieta [VerfasserIn]
Contreras-Figueroa, Elena [VerfasserIn]
Ramos-Languren, Laura E [VerfasserIn]
Ibarra, Clemente [VerfasserIn]
Carreón-Rodríguez, Alfonso [VerfasserIn]
Aschner, Michael [VerfasserIn]
Königsberg, Mina [VerfasserIn]
Santamaría, Abel [VerfasserIn]

Links:

Volltext

Themen:

6-hydroxydopamine
8HW4YBZ748
Dopamine
Dopaminergicmarkers.
EC 1.14.16.2
Enteric nervous system
Journal Article
Oxidopamine
Parkinson’s disease
Replacement therapy
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Stem cells.
Tyrosine 3-Monooxygenase
VTD58H1Z2X

Anmerkungen:

Date Completed 14.06.2021

Date Revised 14.06.2021

published: Print

Citation Status MEDLINE

doi:

10.2174/1871527319666200417123948

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308879899