The central renin–angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans DOI
Ting Xu, Zhiyi Chen, Xinqi Zhou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(8)

Published: Feb. 13, 2024

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in regulation of cognition and behavior as well neuropathology neurological mental disorders. The II type 1 receptor (AT1R) mediates most functional neuropathology-relevant actions associated with central RAS. However, an overarching comprehension to guide translation utilize therapeutic potential RAS humans is currently lacking. We conducted comprehensive characterization using innovative combination transcriptomic gene expression mapping, image-based behavioral decoding, pre-registered randomized controlled discovery–replication pharmacological resting-state magnetic resonance imaging (fMRI) trials (N = 132) selective AT1R antagonist. exhibited particular dense subcortical network encompassing thalamus, striatum, amygdalo-hippocampal formation. Behavioral decoding map showed association memory, stress, reward, motivational processes. Transient blockade further decreased neural activity systems characterized by high expression, while increasing connectivity cortico-basal ganglia-thalamo-cortical circuitry. Effects on level were specifically signatures dopaminergic, opioid, acetylcholine, corticotropin-releasing hormone signaling systems. robustness results was supported independent fMRI trial. These findings present biologically informed pathways their relevance humans.

Language: Английский

The central renin–angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans DOI
Ting Xu, Zhiyi Chen, Xinqi Zhou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(8)

Published: Feb. 13, 2024

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in regulation of cognition and behavior as well neuropathology neurological mental disorders. The II type 1 receptor (AT1R) mediates most functional neuropathology-relevant actions associated with central RAS. However, an overarching comprehension to guide translation utilize therapeutic potential RAS humans is currently lacking. We conducted comprehensive characterization using innovative combination transcriptomic gene expression mapping, image-based behavioral decoding, pre-registered randomized controlled discovery–replication pharmacological resting-state magnetic resonance imaging (fMRI) trials (N = 132) selective AT1R antagonist. exhibited particular dense subcortical network encompassing thalamus, striatum, amygdalo-hippocampal formation. Behavioral decoding map showed association memory, stress, reward, motivational processes. Transient blockade further decreased neural activity systems characterized by high expression, while increasing connectivity cortico-basal ganglia-thalamo-cortical circuitry. Effects on level were specifically signatures dopaminergic, opioid, acetylcholine, corticotropin-releasing hormone signaling systems. robustness results was supported independent fMRI trial. These findings present biologically informed pathways their relevance humans.

Language: Английский

Citations

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