|LETTER TO THE EDITOR
|Year : 2021 | Volume
| Issue : 3 | Page : 218-219
The downregulation of angiotensin-converting enzyme 2 expression may be associated with depression and anxiety among patients with severe acute respiratory syndrome Coronavirus 2
Chidiebere Emmanuel Okechukwu
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
|Date of Submission||02-May-2021|
|Date of Decision||10-May-2021|
|Date of Acceptance||13-May-2021|
|Date of Web Publication||05-Jul-2021|
Dr. Chidiebere Emmanuel Okechukwu
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Okechukwu CE. The downregulation of angiotensin-converting enzyme 2 expression may be associated with depression and anxiety among patients with severe acute respiratory syndrome Coronavirus 2. Curr Med Issues 2021;19:218-9
|How to cite this URL:|
Okechukwu CE. The downregulation of angiotensin-converting enzyme 2 expression may be associated with depression and anxiety among patients with severe acute respiratory syndrome Coronavirus 2. Curr Med Issues [serial online] 2021 [cited 2021 Oct 27];19:218-9. Available from: https://www.cmijournal.org/text.asp?2021/19/3/218/320657
According to a study conducted in Brazil, anxiety, and depression were the most prevalent psychiatric symptoms of coronavirus disease 2019 (COVID-19) in the general population. Several patients with COVID-19 often battle with depression and anxiety., Depression and anxiety are associated with noncompliance to medical treatment., A positive correlation was found between depression, anxiety, and perceived stress among hospitalized patients with COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19. The angiotensin-converting enzyme 2 (ACE2), is the entry receptor for SARS-CoV-2. SARS-CoV-2 competes with angiotensin II (Ang II) for ACE2. The SARS-CoV-2 penetrates the host cell through communicating with the ACE2 receptor through its spike protein, followed by the downregulation of ACE2 expression which eventually upregulates Ang II. The Ang II is a product of the renin-angiotensin system formed by the cleavage of Ang I by the enzyme ACE. The upregulated Ang II interacts with its receptor Ang II receptor type 1 (AT1R) and modifies the gene expression of several inflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells signaling. This Ang II/AT1R interaction also effects the macrophage activation that in turn produces the inflammatory cytokines, thus inducing acute respiratory distress syndrome. However, some metalloproteases (e.g., A disintegrin and metalloprotease 17) breaks down proinflammatory cytokines and ACE2 receptors to the soluble form which facilitates loss of the protective function of surface ACE2 and may increase SARS-CoV-2 pathogenesis. The binding of SARS-CoV-2 with ACE2, and the subsequent downregulation of ACE2 activities, significantly reduce the expression of ACE2 in the cell membranes.
The interactions between angiotensin and dopamine receptors have been observed in cells containing both angiotensin and dopamine receptors in peripheral tissues,, and in the basal ganglia, where counterregulatory interaction between dopamine and angiotensin receptors were observed in the striatum and substantia nigra. The receptor-mediated interactions may be responsible for the modulation of dopamine-mediated behavioral responses by antagonists of the AT1R and inhibitors of ACE. Ang II type 2 receptor stimulation reduced dopamine synthesis in the rat striatum. Animals with genetic alterations in the expression of ACE2 develop a distinct pattern of phenotypes which include behavioral dysfunctions, impairments in serotonin synthesis, and neurogenesis.
ACE2 and dopa decarboxylase (DDC) co-express and co-regulate in non-neuronal cell types. Reduction in ACE2 expression may also decrease DDC expression, thus altering the biosynthesis of dopamine and serotonin, because DDC catalyzes the biosynthesis of dopamine and serotonin. The possible biological mechanism linking ACE2 down-regulation with concomitant downregulation of DDC remains unclear. Low levels of serotonin and dopamine are associated with depression and anxiety. SARS-CoV-2 induced altered expression of ACE2 may as well induce DDC dysfunction, which could possibly decrease the levels of monoamine neurotransmitters in patients with COVID-19.
This is supported by studies in ACE2 knockout mice which showed that these mice produced significantly lower levels of serotonin. This demonstrates that the reduction of ACE2 may possibly decrease brain serotonin levels. According to the multi experiment matrix, an advanced web tool that integrates and merge relationship ties between messenger RNA levels across human microarray datasets, the gene that presented the most statistically significant co-expression relationship with ACE2 is the DDC gene.
DDC as a key enzyme of the dopamine and the serotonin pathways converts L-3,4-dihydroxyphenylalanine to dopamine and L-5-hydroxytryptophan to serotonin. ACE2 potential coregulation with DDC could signify a possible biological association between the ACE2-mediated synthesis of angiotensin (1–7) and the DDC-mediated synthesis of dopamine and serotonin. Although, dopamine and angiotensin systems directly counterregulate each other in renal cells.
In conclusion, SARS-CoV-2 downregulation of ACE2 expression may possibly reduce DDC expression, because ACE2 and DDC co-express and co-regulate in several cell types, which could decrease the levels of serotonin and dopamine in patients with COVID-19, resulting to depression and anxiety. However, further studies are needed to substantiate the biological relationship between the SARS-CoV-2 induced downregulation of ACE2, and the prevalence of depression and anxiety among patients with COVID-19.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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