SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

Marinescu, Ileana; Marinescu, D.; Mogoantă, Laurențiu; Efrem, Ion Cristian; Stovicek, Puiu Olivian

doi:10.47162/rjme.61.4.03

Cited by 10 publications

(12 citation statements)

References 152 publications

(160 reference statements)

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“…Moreover, our proteomic analysis of hamsters’ brains in vivo compared to human single‐cell RNA sequencing datasets corroborates the importance of the metabolic and energetic imbalance of glutamate/glutamine that may take place in the brain of neurological COVID‐19 patients. Our data bring attention not only to the physiology of the COVID‐19 brain, but also suggest that glutamate/glutamine signaling is pivotal, and may be considered either a prognostic factor or a target of specific therapies in patients that develop the neurological impairments observed during long‐covid and PASC, as memory loss and cognitive decline, and as already discussed elsewhere (Figure 7; Marinescu et al, 2020).…”

Section: Discussionsupporting

confidence: 74%

SARS‐CoV‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

Oliveira

Angelo

Yamamoto

et al. 2022

Journal of Neurochemistry

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COVID‐19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID‐19. Here we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS‐CoV‐2 infected Syrian hamsters. We show that SARS‐CoV‐2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real‐time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro . SARS‐CoV‐2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID‐19, as memory loss, confusion, and cognitive impairment.

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Section: Discussionsupporting

confidence: 74%

SARS‐CoV‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

Oliveira

Angelo

Yamamoto

et al. 2022

Journal of Neurochemistry

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“…Clinical and animal studies have confirmed associations of decreased hippocampal volume and weight and apoptosis with depression. Hippocampal injury (hippocampal volume reduction and excessive neuronal death) is considered an important marker of the pathogenesis of depression [ 5 , 6 ]. Numerous studies have linked apoptosis to hippocampus damage.…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Helicid Improves Lipopolysaccharide‐Induced Apoptosis of C6 Cells by Regulating SH2D5 DNA Methylation via the CytC/Caspase9/Caspase3 Signaling Pathway

Zhang

Wang

Zhang

et al. 2022

Contrast Media & Molecular Imaging

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DNA methylation is reportedly associated with stress responses and depression. Treatment with antidepressants can regulate DNA methylation and, subsequently, gene expression in the hippocampus. Hence, DNA methylation is a potential target for treatment of depression. Screening of high-throughput data of a rat model of chronic unpredictable mild stress revealed relatively low expression of SH2 domain-containing 5 (SH2D5). SH2D5 can be overexpressed by treatment with helicid. Therefore, in order to further explore the role of SH2D5 in depression and whether helicid mediates the DNA methylation of SH2D5 as a potential antidepressant role, SH2D5 was overexpressed in C6 cells as a lipopolysaccharides (LPS)-induced model of depression. The expression levels of Bax, Bcl-2, Bad, and Daxx, and changes to the CytC/caspase9/caspase3 signal pathway were detected by qRT-PCR and Western blot analyses. After treatment with helicid or silencing of SH2D5, the above indices were detected. The results showed that helicid regulated the CytC/caspase9/caspase3 signaling pathway and improved the apoptosis indices of C6 cells through the overexpression of SH2D5. Interestingly, silencing of SH2D5 reversed the effects of helicid on the above indices. Then, in order to study the underlying mechanism, the cells were administered to helicid or 5-aza-2′-deoxycytidine (5-AzaD) and expression of SH2D5 was detected by qRT-PCR and Western blot analyses, while to assess the DNA methylation level of SH2D5 using bisulfite sequencing/PCR. The results showed that SH2D5 was hypermethylated with low expression in LPS-induced C6 cells, which was reversed by helicid and 5-AzaD. These results suggest that helicid may affect the CytC/caspase9/caspase3 apoptosis signaling pathway and improve the apoptosis indices by mediating DNA methylation of SH2D5.

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“…In vitro experiments illustrated that memantine inhibits the SARS-CoV-2 E protein which is necessary for pathogenesis and viral proliferation (Matsunaga et al 2018 ). As well, NMDA antagonists like memantine and amantadine could be used as prophylactic agents and reduce neuropsychiatric complications in COVID-19 patients (Marinescu et al 2020 ). Memantine also reduced HCoV‐OC43 replication in the CNS, indicating that it could be utilized as an anti-viral agent and improve neurological diseases.…”

Section: Role Of Nachr Agonists/antagonists In Covid-19mentioning

confidence: 99%

“…So, memantine could be effective against the development of symptomatic COVID-19. As well, memantine can provide protection for olfactory neurocircuits, decrease the aggressiveness of NMDA receptor hyperactivity, alveolar protection, and regulate cytokine mechanisms (Marinescu et al 2020 ).…”

Section: Role Of Nachr Agonists/antagonists In Covid-19mentioning

confidence: 99%

Cholinergic dysfunction in COVID-19: frantic search and hoping for the best

Nadwa

Al-Kuraishy

Al-Gareeb

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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A novel coronavirus known as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a potential cause of acute respiratory infection called coronavirus disease 2019 (COVID-19). The binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2) induces a series of inflammatory cellular events with cytopathic effects leading to cell injury and hyperinflammation. Severe SARS-CoV-2 infection may lead to dysautonomia and sympathetic storm due to dysfunction of the autonomic nervous system (ANS). Therefore, this review aimed to elucidate the critical role of the cholinergic system (CS) in SARS-CoV-2 infection. The CS forms a multi-faceted network performing diverse functions in the body due to its distribution in the neuronal and non-neuronal cells. Acetylcholine (ACh) acts on two main types of receptors which are nicotinic receptors (NRs) and muscarinic receptors (MRs). NRs induce T cell anergy with impairment of antigen-mediated signal transduction. Nicotine through activation of T cell NRs inhibits the expression and release of the pro-inflammatory cytokines. NRs play important anti-inflammatory effects while MRs promote inflammation by inducing the release of pro-inflammatory cytokines. SARS-CoV-2 infection can affect the morphological and functional stability of CS through the disruption of cholinergic receptors. SARS-CoV-2 spike protein is similar to neurotoxins, which can bind to nicotinic acetylcholine receptors (nAChR) in the ANS and brain. Therefore, cholinergic receptors mainly nAChR and related cholinergic agonists may affect the pathogenesis of SARS-CoV-2 infection. Cholinergic dysfunction in COVID-19 is due to dysregulation of nAChR by SARS-CoV-2 promoting the central sympathetic drive with the development of the sympathetic storm. As well, nAChR activators through interaction with diverse signaling pathways can reduce the risk of inflammatory disorders in COVID-19. In addition, nAChR activators may mitigate endothelial dysfunction (ED), oxidative stress (OS), and associated coagulopathy in COVID-19. Similarly, nAChR activators may improve OS, inflammatory changes, and cytokine storm in COVID-19. Therefore, nAChR activators like varenicline in virtue of its anti-inflammatory and anti-oxidant effects with direct anti-SARS-CoV-2 effect could be effective in the management of COVID-19.

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SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

Cited by 10 publications

References 152 publications

SARS‐CoV‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

SARS‐CoV‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

[Retracted] Helicid Improves Lipopolysaccharide‐Induced Apoptosis of C6 Cells by Regulating SH2D5 DNA Methylation via the CytC/Caspase9/Caspase3 Signaling Pathway

Cholinergic dysfunction in COVID-19: frantic search and hoping for the best

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