This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Javier Stern
Georgia State University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The cellular mechanisms underlying cognitive impairments in heart failure (HF) remain unknown. Although HF-induced neuroinflammation and hypoxia in the hippocampus have been reported in humans and rodents, whether and how these processes are causally connected remains unexplored. Here we report that microglial Angiotensin II (AngII) signaling in the hippocampus is a crucial component in HF-induced neuroinflammation. We found microglial-specific upregulation of the AngII receptor AT1a that coincided with a hypoxic state, but preceded cytokine production. In addition to hippocampal apoptotic clusters, HF rats displayed progressive angiogenesis, migration of AT1a-positive microglia to blood vessels, and disruption of BBB integrity. Treatment of HF rats with the AT1 receptor antagonist losartan reversed neuroinflammation (but not hypoxia), apoptosis and cognitive impairments in HF rats. Taken together, we present here a novel mechanism by which microglial AngII signaling triggers a microglia-dependent neuroinflammatory cascade that contributes to neuronal apoptosis, hippocampal structure deterioration and cognitive decline.
Keywords
microglial Angiotensin II, heart failure, cognitive decline
This preprint is available for download as a PDF.
There is NO Competing Interest.
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Oct, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Article
Javier Stern
Georgia State University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 Oct, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The cellular mechanisms underlying cognitive impairments in heart failure (HF) remain unknown. Although HF-induced neuroinflammation and hypoxia in the hippocampus have been reported in humans and rodents, whether and how these processes are causally connected remains unexplored. Here we report that microglial Angiotensin II (AngII) signaling in the hippocampus is a crucial component in HF-induced neuroinflammation. We found microglial-specific upregulation of the AngII receptor AT1a that coincided with a hypoxic state, but preceded cytokine production. In addition to hippocampal apoptotic clusters, HF rats displayed progressive angiogenesis, migration of AT1a-positive microglia to blood vessels, and disruption of BBB integrity. Treatment of HF rats with the AT1 receptor antagonist losartan reversed neuroinflammation (but not hypoxia), apoptosis and cognitive impairments in HF rats. Taken together, we present here a novel mechanism by which microglial AngII signaling triggers a microglia-dependent neuroinflammatory cascade that contributes to neuronal apoptosis, hippocampal structure deterioration and cognitive decline.
This preprint is available for download as a PDF.
There is NO Competing Interest.
Loading...