Deregulation of ceRNA Networks in Frontal Cortex and Choroid Plexus of Brain during SARS‐CoV‐2 Infection Aggravates Neurological Manifestations: An Insight from Bulk and Single‐Cell Transcriptomic Analyses

Abstract

CSF) of patients with Parkinson's disease (PD) [5] and found to be potent in causing neurodegeneration by invading the neurons. [6] SARS-CoV-2 belongs to the family of these coronaviruses and it was also found to be neuro-invasive. [7] In addition to that, the cytokine storm due to SARS-CoV-2 infection is massively exhibited by a hyperinflammatory response. [8] The chronic neuroinflammation induced by cytokine storm is also being treated as a marker of neurodegenerative diseases like Alzheimer's (AD), PD, and Huntington's disease (HD). [9] During AD progression, pro-inflammatory cytokines like IL-1 and IL-6 inhibit phagocytosis of beta-amyloid (Aβ) by microglia and so its accumulation causes neuroinflammation. [10] Whereas, in CSF of PD patients, tumor necrosis factor (TNF) was reported to be responsible for neuronal death in fatal cases. [11] Intriguingly, neuroinflammation was also found to instigate psychiatric diseases by elicitation of microglial response, altering neuroplasticity, cognition, and behavior. [12] Thus, aggravation of neuroinflammatory responses by cytokine storm of SARS-CoV-2 might cause neurological manifestations in the future.As per reports from the epicenter of COVID-19-Wuhan, China, the most common neurological manifestation of SARS-CoV-2 included dizziness, headache, impaired consciousness, seizures, and acute cerebrovascular disease. [13] A recent report suggested that a COVID-19 patient symptomized by fever and abnormal mental status was diagnosed with acute necrotizing encephalopathy which is characterized by blood-brain barrier (BBB) disruption due to intracranial cytokine storm. [14] Hence, neurological manifestations are emerging as an aftermath of COVID-19. Due to the lack of experimental studies in pandemic situation, in silico studies have been priming COVID-19 research by digging into the utter complexities that might be associated with the comorbidities. [15,16] Several studies with human brain organoids reveal a varying degree of neurotropism for SARS-CoV-2. [17,18] Since the brain is a complex heterogeneous tissue consisting of various cell types like-glial, epithelial, and neural cells, [19] so to understand neurological manifestations of SARS-CoV-2 infection, studies should be conducted at the Although transcriptomic studies of SARS-CoV-2-infected brains have depicted variability in gene expression, the landscape of deregulated cell-specific regulatory circuits has not been elucidated yet. Hence, bulk and single-cell RNA-seq data are analyzed to gain detailed insights. Initially, two ceRNA networks with 19 and 3 differentially expressed (DE) hub lncRNAs are reconstructed in SARS-CoV-2 infected Frontal Cortex (FC) and Choroid Plexus (CP), respectively. Functional and pathway enrichment analyses of downstream mRNAs of deregulated ceRNA axes demonstrate impairment of neurological processes. Mapping of hub lncRNA-mRNA pairs from bulk RNA-seq with snRNA-seq data has indicated that NORAD, NEAT1, and STXBP5-AS1 are downregulated across 4, 4, and 2 FC cell types, respectively. At ...

Associations between brain gene expression perturbations implicated by COVID-19 and psychiatric disorders

“…Moreover, researches also demonstrated SARS-CoV-2 infection damaged the epithelium of choroid plexus and disrupted the blood-cerebrospinal fluid barrier in human brain organoids ( Pellegrini et al, 2020 ), ( Jacob et al, 2020 ), and the single-cell RNA sequencing study identified broad cellular perturbations and inflammation of choroid plexus in severe COVID-19 ( Yang et al, 2021 ). Besides, a recently published study also identified genes, as well as long non-coding RNAs that were dis-regulated in neurons of choroid plexus after SARS-CoV-2 infection ( Das and Podder, 2022 ). It was indicated that neurological complications of COVID-19 might arise more commonly due to aberrant inflammation throughout CNS, which might be relayed by the choroid plexus ( Thompson et al, 2022 ).…”