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Impact of Muscarinic Receptor Activation on Neural Stem Cell Differentiation

Ge, Shufan
http://rave.ohiolink.edu/etdc/view?acc_num=mco1291827018

Abstract Details

2010, Master of Science in Pharmaceutical Science (MSP), University of Toledo, College of Pharmacy.
Since neurogenesis was demonstrated in adult mammalian brain, the field of neural stem cell (NSC) research has been in a state of rapid growth. However, it is still not very clear when and how NSCs begin to differentiate into other cell types and express different proteins. Recent studies suggest that some neurotransmitters such as acetylcholine (Ach) are involved in the proliferation as well as the differentiation process of NSCs. The aim of the present study was to determine the role of muscarinic receptors in the process of differentiation in NSCs. In the present studies, we used NSCs from the hippocampus of the adult rat brain and cultured them in differentiation media. The expression of different protein markers such as nestin and GFAP was observed by cell imaging. There was a strong expression of both nestin and GFAP in astrocytes, but not in cells developing in neuronal pathways. The expression of GFAP was significantly increased after NSCs were differentiated into astrocytes. A study was then done to understand the effects of muscarinic receptor activation on NSCs during differentiation. The expression of mRNA for the five muscarinic receptor subtypes was determined using the RT-PCR technique in different types of cells. The m3 mAChR mRNA was the only subtype detected in each cell type. Carbachol was used as a cholinergic agonist to stimulate muscarinic receptors in NSCs in the present studies. Under the conditions we used, carbachol had no significant effect on the expression of nestin or GFAP in the process of differentiation, which suggests that carbachol does not promote differentiation into neuronal or astrocytic cells in NSCs. Since extracellular signal-regulated kinase (Erk 1/2) phosphorylated after treatment with carbachol, and it is a marker for proliferation in many cell types, we examined the stimulation of ERK1/2 by carbachol in neural stem cells and astrocytes. Through immunoblotting and immunohistochemistry, we observed a rapid phosphorylation of ERK1/2 in stem cells as well as astrocytes after carbachol treatment for 5 minutes. The maximal stimulation was achieved at 0.1 mM carbachol in both cell types, accompanied by a decrease in total ERK(1/2) expression. Additional studies are necessary to understand the physiological significance of inducing ERK(1/2) activation.
William Messer (Committee Chair)
Surya Nauli (Committee Member)
Youssef Sari (Committee Member)
54 p.
Pharmacology
muscarinic receptors; neural stem cells; differentiation

Recommended Citations

Citations

  • Ge, S. (2010). Impact of Muscarinic Receptor Activation on Neural Stem Cell Differentiation [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1291827018

    APA Style (7th edition)

  • Ge, Shufan. Impact of Muscarinic Receptor Activation on Neural Stem Cell Differentiation. 2010. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1291827018.

    MLA Style (8th edition)

  • Ge, Shufan. "Impact of Muscarinic Receptor Activation on Neural Stem Cell Differentiation." Master's thesis, University of Toledo, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1291827018

    Chicago Manual of Style (17th edition)

mco1291827018
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© 2010, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.