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内容記述 |
The chemogenetic technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), offers a means to reversibly control the activity of a target cell population expressing a designer receptor by systemic administration of an inert actuators. While muscarinic-based DREADDs, such as hM3Dq (excitatory) and hM4Di (inhibitory), are widely used in rodent studies, their application in primate models is less documented. Understanding the temporal patterns of DREADD expression is crucial for planning long-term experiments in monkeys, as the effectiveness of chemogenetic control depends on the levels of DREADD expression. In this study, we longitudinally quantified in vivo DREADD expression in macaque monkeys using positron emission tomography with the DREADD-selective tracer [11C]deschloroclozapine (DCZ), complemented by functional studies. Twenty macaque monkeys were evaluated after being injected with adeno-associated virus vectors expressing the DREADDs hM4Di or hM3Dq, whose expression was quantified as changes in [11C]DCZ binding potential from baseline levels. Expression levels of both hM4Di and hM3Dq peaked around 60 days post-injection, remained stable for about 1.5 years, and declined gradually after two years. Significant chemogenetic control of neural activity and behavior persisted for about two years. Virus titer and the presence of protein tags significantly influenced expression levels, with co-expressed protein tags reducing overall expression levels. These findings provide valuable insights and guidelines for optimizing the use of DREADDs in long-term primate studies and potential therapeutic applications. |
