Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells.

Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Research Abstract Details 

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Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Abstract Text:

Stem cells have been widely assumed to be capable of replacing lost or damaged cells in a number of diseases, including Parkinson's disease (PD), in which neurons of the substantia nigra (SN) die and fail to provide the neurotransmitter, dopamine (DA), to the striatum. We report that undifferentiated human neural stem cells (hNSCs) implanted into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Parkinsonian primates survived, migrated, and had a functional impact as assessed quantitatively by behavioral improvement in this DA-deficit model, in which Parkinsonian signs directly correlate to reduced DA levels. A small number of hNSC progeny differentiated into tyrosine hydroxylase (TH) and/or dopamine transporter (DAT) immunopositive cells, suggesting that the microenvironment within and around the lesioned adult host SN still permits development of a DA phenotype by responsive progenitor cells. A much larger number of hNSC-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells. These hNSCs, which express DA-protective factors, were therefore well positioned to influence host TH+ cells and mediate other homeostatic adjustments, as reflected in a return to baseline endogenous neuronal number-to-size ratios, preservation of extant host nigrostriatal circuitry, and a normalizing effect on alpha-synuclein aggregation. We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD.

Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Publishing Authors By Initials

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Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 12175-80

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 22

MONTH: 06

YEAR: 2007

Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Keywords Mesh Terms:

KEYWORDS: Stem Cells

MESH TERMS: cytology

Chemical & Substance for Abstract: Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Information

Substance Name: Dopamine

Registry Number: 51-61-6

Grant and Affiliation Information for Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells.

AFFILIATION: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32GM08666

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE: Proc Natl Acad Sci U S A. 2007 Jul 17;10

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