The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.
Keyphrases
- angiotensin converting enzyme
- angiotensin ii
- sars cov
- coronavirus disease
- signaling pathway
- poor prognosis
- genome wide
- high glucose
- diabetic rats
- metabolic syndrome
- gene expression
- mass spectrometry
- small molecule
- cell proliferation
- induced apoptosis
- replacement therapy
- subarachnoid hemorrhage
- cerebrospinal fluid
- genome wide analysis