In vivo production and release of acetylcholine from primary fibroblasts genetically modified to express choline acetyltransferase.

Abstract:

:Primary rat fibroblasts genetically modified to express Drosophila choline acetyltransferase (dChAT) synthesize and release acetylcholine (ACh) in vitro. The ACh produced from the transduced fibroblasts was found to be enhanced by increasing amounts of choline chloride in the culture media. These dChAT-expressing cells were then implanted into the intact hippocampus of adult rats and in vivo microdialysis was performed 7-10 days after grafting to assess the ability of the cells to produce ACh and respond to exogenous choline in vivo. Samples collected from anesthetized rats revealed fourfold higher levels of ACh around dChAT grafts than from either non-grafted or control-grafted hippocampi. Localized choline infusion (200 microM) through the dialysis probes was found to induce a selective twofold increase in ACh release only from the dChAT-expressing fibroblasts. These results indicate not only that dChAT-expressing fibroblasts continue to synthesize and secrete ACh for at least 10 days after intracerebral grafting, but that the levels of ACh can be manipulated in vivo. The ability to regulate products within genetically modified cells in vivo may provide a powerful avenue for exploring the role of discrete substances within the CNS.

journal_name

J Neurochem

authors

Fisher LJ,Schinstine M,Salvaterra P,Dekker AJ,Thal L,Gage FH

doi

10.1111/j.1471-4159.1993.tb13625.x

subject

Has Abstract

pub_date

1993-10-01 00:00:00

pages

1323-32

issue

4

eissn

0022-3042

issn

1471-4159

journal_volume

61

pub_type

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