DREADDs-Based Chemogenetics Induced Slow Transit Constipation via Inhibition of Enteric Neurons.

ABSTRACT:

Objectives

Designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools are commonly used to activate or silence targeted neurons by the agonistic ligand deschloroclozapine (DCZ). This study aimed to establish a Gi-DREADD-based murine model of slow transit constipation (STC) and elucidate its pathophysiological mechanisms.

Methods

Adeno-associated virus (AAV) 9-hM4Di was injected into the intestinal wall of mice, and colonic motility was evaluated. The efficiency and immunogenicity of AAV9-hM4Di transduction in the enteric nervous system (ENS) were evaluated. Nitric oxide (NO), acetylcholine (ACh), and substance P (SP) in the colonic tissues and serum samples were analyzed. Calcium (Ca²⁺) imaging was performed to evaluate the respo

SUBMITTER: Lu XY 

PROVIDER: S-EPMC12038534 | biostudies-literature | 2025 Jan-Feb

REPOSITORIES: biostudies-literature