Effects of Varying Glucose Concentrations on ACE2′s Hypothalamic Expression and Its Potential Relation to COVID-19-Associated Neurological Dysfunction

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted millions of lives, despite several vaccine interventions and strict precautionary measures. The main causative organism of this disease is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which infects the host via two key players: the angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2). Some reports revealed that patients with glycemic dysregulation could have increased susceptibility to developing COVID-19 and its related neurological complications. However, no previous studies have looked at the involvement of these key molecules within the hypothalamus, which is the central regulator of glucose in the brain. By exposing embryonic mouse hypothalamic neurons to varying glucose concentrations, we aimed to investigate the expression of ACE2 and TMPRSS2 using quantitative real time polymerase chain reaction and western blotting. A significant and time-dependent increase and decrease was observed on the viability of hypothalamic neurons with increasing and decreasing glucose concentrations, respectively (p < 0.01 and p < 0.001, respectively). Under the same increasing and decreasing glucose conditions, the expression of hypothalamic ACE2 also revealed a significant and time-dependent increase (p < 0.01). These findings suggest that SARS-CoV-2 invades the hypothalamic circuitry. In addition, it highlights the importance of strict glycemic control for COVID-19 in diabetic patients.