Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine.

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Research Abstract Details 

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Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Abstract Text:

Amelia Marutle,Masao Ohmitsu,Mats Nilbratt,Nigel H Greig,Agneta Nordberg,Kiminobu Sugaya,

In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) may prevent neuronal differentiation of HNSCs. Thus, successful neuroplacement therapy for AD may require regulating APP expression to favorable levels to enhance neuronal differentiation of HNSCs. Phenserine, a recently developed cholinesterase inhibitor (ChEI), has been reported to reduce APP levels in vitro and in vivo. In this study, we found reductions of APP and glial fibrillary acidic protein (GFAP) levels in the hippocampus of APP23 mice after 14 days treatment with (+)-phenserine (25 mg/kg) lacking ChEI activity. No significant change in APP gene expression was detected, suggesting that (+)-phenserine decreases APP levels and reactive astrocytes by posttranscription regulation. HNSCs transplanted into (+)-phenserine-treated APP23 mice followed by an additional 7 days of treatment with (+)-phenserine migrated and differentiated into neurons in the hippocampus and cortex after 6 weeks. Moreover, (+)-phenserine significantly increased neuronal differentiation of implanted HNSCs in hippocampal and cortical regions of APP23 mice and in the CA1 region of control mice. These results indicate that (+)-phenserine reduces APP protein in vivo and increases neuronal differentiation of HNSCs. Combination use of HNSC transplantation and treatment with drugs such as (+)-phenserine that modulate APP levels in the brain may be a useful tool for understanding mechanisms regulating stem cell migration and differentiation during neurodegenerative conditions in AD.

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Publishing Authors By Initials

A Marutle,M Ohmitsu,M Nilbratt,NH Greig,A Nordberg,K Sugaya,

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Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 12506-11

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

ISSN: 0027-8424

DAY: 17

MONTH: 07

YEAR: 2007

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Keywords Mesh Terms:

KEYWORDS: Stem Cells

MESH TERMS: drug effects

Chemical & Substance for Abstract: Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Information

Substance Name: Physostigmine

Registry Number: 57-47-6

Grant and Affiliation Information for Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine.

AFFILIATION: Biomolecular Sciences Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA. amelia.marutle@ki.se

Country: United States

AGENCY: United States NIA

GRANT: AG 23472

ACRONYM: AG

MEDLINETA: Proc Natl Acad Sci U S A

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