ACE2 Receptor and TMPRSS2 Protein Expression Patterns in the Human Brainstem Reveal Anatomical Regions Potentially Vulnerable to SARS-CoV-2 Infection

Angiotensin-convertingenzyme 2 receptor (ACE2R) is a transmembraneprotein expressed in various tissues throughout the body that playsa key role in the regulation of blood pressure. Recently, ACE2R hasgained significant attention due to its involvement in the pathogenesisof COVID-19, the disease caused by the Severe Acute Respiratory SyndromeCoronaVirus 2 (SARS-CoV-2). While ACE2 receptors serve as entry pointsfor the novel coronavirus, Transmembrane Serine Protease 2 (TMPRSS2),an enzyme located on the cell membrane, is required for SARS-CoV-2S protein priming. Even though numerous studies have assessed theeffects of COVID-19 on the brain, very little information is availableconcerning the distribution of ACE2R and TMPRSS2 in the human brain,with particular regard to their topographical expression in the brainstem.In this study, we investigated the expression of ACE2R and TMPRSS2in the brainstem of 18 adult subjects who died due to pneumonia/respiratoryinsufficiency. Our findings indicate that ACE2R and TMPRSS2 are expressedin neuronal and glial cells of the brainstem, particularly at thelevel of the vagal nuclei of the medulla and the midbrain tegmentum,thus confirming the expression and anatomical localization of theseproteins within specific human brainstem nuclei. Furthermore, ourfindings help to define anatomically susceptible regions to SARS-CoV-2infection in the brainstem, advancing knowledge on the neuropathologicalunderpinnings of neurological manifestations in COVID-19.

Automated summary

Angiotensin-converting enzyme 2 receptor (ACE2R) is a transmembrane protein that plays a key role in blood pressure regulation. It has gained attention for its involvement in the pathogenesis of COVID-19. This study investigated the expression of ACE2R and TMPRSS2 in the brainstem and found that they are expressed in neuronal and glial cells, particularly in specific nuclei. These findings help to understand the neurological manifestations of COVID-19.