Identification of angiotensin II-responsive circadian clock gene expression in adrenal zona glomerulosa cells and human adrenocortical H295R cells

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

The mammalian circadian timing system is organized in a hierarchy, with the master clock residing suprachiasmatic nucleus (SCN) of hypothalamus and subsidiary peripheral clocks tissues. Because diversity tissues cell-types body, existence autonomous identification its potential entrainment signals need to be empirically defined on cell type-by-cell type basis. In this study, we characterized basic properties adrenal zona glomerulosa cells, or ZG cells. Using isolated explants from Per2 Luc mice, dissociated cells Per2-dluc rats, related human adrenocortical line H295R, showed that possess genetically-encoded, self-sustained cell-autonomous clock. As signals, angiotensin II (Ang II) caused phase-dependent phase-shifts cultured slices. Ang treatment also drove initiation (or reset) gene expression H295R associated immediate up-regulation PER1 E4BP4 mRNA expression. We found I receptor blocker CV11974, one most widely used clinical drugs for hypertensive diseases, attenuation phase resetting Our vitro data provide basis understand argue gland as component entrainable clocks.

Language: Английский

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Longitudinal assessment of DREADD expression and efficacy in the monkey brain

Published: April 2, 2025

Designer Receptors Exclusively Activated by Drugs (DREADDs) offer a powerful means for reversible control of neuronal activity through systemic administration inert actuators. Because chemogenetic relies on DREADD expression levels, understanding and quantifying the temporal dynamics their is crucial planning long-term experiments in monkeys. In this study, we longitudinally quantified vivo macaque monkeys using positron emission tomography with DREADD-selective tracer [ 11 C]deschloroclozapine (DCZ), complemented functional studies. Twenty were evaluated after being injected adeno-associated virus vectors expressing DREADDs hM4Di or hM3Dq, whose was as changes C]DCZ binding potential from baseline levels. Expression levels both hM3Dq peaked around 60 days post-injection, remained stable about 1.5 years, declined gradually two years. Significant neural behavior persisted Virus titer presence protein tags significantly influenced co-expressed reducing overall These findings provide valuable insights guidelines optimizing use primate studies therapeutic applications.

Language: Английский

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Longitudinal assessment of DREADD expression and efficacy in the monkey brain

Published: April 2, 2025

Designer Receptors Exclusively Activated by Drugs (DREADDs) offer a powerful means for reversible control of neuronal activity through systemic administration inert actuators. Because chemogenetic relies on DREADD expression levels, understanding and quantifying the temporal dynamics their is crucial planning long-term experiments in monkeys. In this study, we longitudinally quantified vivo macaque monkeys using positron emission tomography with DREADD-selective tracer [ 11 C]deschloroclozapine (DCZ), complemented functional studies. Twenty were evaluated after being injected adeno-associated virus vectors expressing DREADDs hM4Di or hM3Dq, whose was as changes C]DCZ binding potential from baseline levels. Expression levels both hM3Dq peaked around 60 days post-injection, remained stable about 1.5 years, declined gradually two years. Significant neural behavior persisted Virus titer presence protein tags significantly influenced co-expressed reducing overall These findings provide valuable insights guidelines optimizing use primate studies therapeutic applications.

Language: Английский

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Longitudinal assessment of DREADD expression and efficacy in the monkey brain

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Abstract Designer Receptors Exclusively Activated by Drugs (DREADDs) offer a powerful means for reversible control of neuronal activity through systemic administration inert actuators. Because chemogenetic relies on DREADD expression levels, understanding and quantifying the temporal dynamics their is crucial planning long-term experiments in monkeys. In this study, we longitudinally quantified vivo macaque monkeys using positron emission tomography with DREADD-selective tracer [ 11 C]deschloroclozapine (DCZ), complemented functional studies. Twenty were evaluated after being injected adeno-associated virus vectors expressing DREADDs hM4Di or hM3Dq, whose was as changes C]DCZ binding potential from baseline levels. Expression levels both hM3Dq peaked around 60 days post-injection, remained stable about 1.5 years, declined gradually two years. Significant neural behavior persisted Virus titer presence protein tags significantly influenced co-expressed reducing overall These findings provide valuable insights guidelines optimizing use primate studies therapeutic applications.

Language: Английский

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