Imaging in vivo acetylcholine release in the peripheral nervous system with a fluorescent nanosensor.

Autor:	Xia J; Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA 02115., Yang H; Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA 02115., Mu M; Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA 02115., Micovic N; Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA 02115., Poskanzer KE; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143.; Kavli Insititute for Fundamental Neuroscience, San Francisco, CA 94143., Monaghan JR; Department of Biology, College of Science, Northeastern University, Boston, MA 02115., Clark HA; Department of Bioengineering, College of Engineering, Northeastern University, Boston, MA 02115; h.clark@northeastern.edu.; Department of Chemistry and Chemical Biology, College of Science, Northeastern University, Boston, MA 02115.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Apr 06; Vol. 118 (14).
DOI:	10.1073/pnas.2023807118
Abstrakt:	The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological diseases. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose dependent, reversible, and we observe a reduction of ∼76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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