Angiotensin-converting
enzyme 2 receptor (ACE2R) is a transmembrane
protein expressed in various tissues throughout the body that plays
a key role in the regulation of blood pressure. Recently, ACE2R has
gained significant attention due to its involvement in the pathogenesis
of COVID-19, the disease caused by the Severe Acute Respiratory Syndrome
CoronaVirus 2 (SARS-CoV-2). While ACE2 receptors serve as entry points
for the novel coronavirus, Transmembrane Serine Protease 2 (TMPRSS2),
an enzyme located on the cell membrane, is required for SARS-CoV-2
S protein priming. Even though numerous studies have assessed the
effects of COVID-19 on the brain, very little information is available
concerning 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 TMPRSS2
in the brainstem of 18 adult subjects who died due to pneumonia/respiratory
insufficiency. Our findings indicate that ACE2R and TMPRSS2 are expressed
in neuronal and glial cells of the brainstem, particularly at the
level of the vagal nuclei of the medulla and the midbrain tegmentum,
thus confirming the expression and anatomical localization of these
proteins within specific human brainstem nuclei. Furthermore, our
findings help to define anatomically susceptible regions to SARS-CoV-2
infection in the brainstem, advancing knowledge on the neuropathological
underpinnings of neurological manifestations in COVID-19.