Immunization with 674–685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice

Lykhmus, Olena; Kalashnyk, Olena; Koval, Lyudmyla; Krynina, O. I.; Komisarenko, Serhiy; Skok, Maryna

doi:10.1016/j.bbrc.2022.07.016

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…Our results confirmed these findings, where we showed a deterioration in memory and spatial learning abilities in diabetics exposed to SARS-CoV-2 spike protein. Our findings were in agreement with Lykhmus et al, who showed that fragment of SARS-CoV-2 spike protein induces neuroinflammation and impairs episodic memory of mice [33].…”

Section: Discussionsupporting

confidence: 94%

SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation

Burnett,

Coucha,

Bolduc

et al. 2023

IJMS

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Diabetics are more vulnerable to SARS-CoV-2 neurological manifestations. The molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetes are unclear. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebrovascular oxidative stress and inflammation via activation of the destructive arm of the renin–angiotensin-aldosterone system (RAAS) and Toll-like receptor (TLR) signaling. SARS-CoV-2 spike protein was injected in humanized ACE2 transgenic knock-in mice. Cognitive functions, cerebral blood flow, cerebrovascular architecture, RAAS, and TLR signaling were used to determine the effect of SARS-CoV-2 spike protein in diabetes. Studies were mirrored in vitro using human brain microvascular endothelial cells treated with high glucose-conditioned media to mimic diabetic conditions. Spike protein exacerbated diabetes-induced cerebrovascular oxidative stress, inflammation, and endothelial cell death resulting in an increase in vascular rarefaction and diminished cerebral blood flow. SARS-CoV-2 spike protein worsened cognitive dysfunction in diabetes compared to control mice. Spike protein enhanced the destructive RAAS arm at the expense of the RAAS protective arm. In parallel, spike protein significantly exacerbated TLR signaling in diabetes, aggravating inflammation and cellular apoptosis vicious circle. Our study illustrated that SAR-CoV-2 spike protein intensified RAAS and TLR signaling in diabetes, increasing cerebrovascular damage and cognitive dysfunction.

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Section: Discussionsupporting

confidence: 94%

SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation

Burnett,

Coucha,

Bolduc

et al. 2023

IJMS

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“…The activation of microglia appeared to be mediated by persistently elevated levels of a molecule called C-C motif chemokine 11 (CCL11). CCL11 has been associated with ageing and with inhibition of neurogenesis [ 177 , 178 ], as well as allergies and the recruitment of eosinophils [ 179 ].…”

Section: Evidence Of ‘Spikeopathy’—spike Protein Pathogenicitymentioning

confidence: 99%

“…Another study looked at the toxin-like domain of the RBG on S1, which binds to α7 nAChR, increasing levels of IL-1b and TNF α in the brain and impaired episodic memory in mice [ 178 ]. As discussed above, the blocking of this receptor with the spike protein could cause very high levels of inflammation since it regulates pro-inflammatory cytokine production.…”

Section: Evidence Of ‘Spikeopathy’—spike Protein Pathogenicitymentioning

confidence: 99%

‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA

Parry,

Lefringhausen,

Turni

et al. 2023

Biomedicines

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The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of ‘safe and effective’ vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the ‘safe and effective’ narrative attached to these new technologies. Spike protein pathogenicity, termed ‘spikeopathy’, whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a ‘synthetic virus’, is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that ‘spikeopathy’ can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely.

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“…The experimental results concerning a possible interaction of the nAChR with the S protein fragments have appeared only very recently. In one publication [ 258 ], it was found that the immunization of mice with peptide 674–685 bound to hemocyanin resulted in decreased levels of α7 nAChRs and in higher levels of TNF-α and IL-1β. In more detail, the effects of the Y674-R685 peptide on α7 nAChRs were analyzed in [ 259 ].…”

Section: α7- and α9-containing Nachrs As Targets In Viral Infectionmentioning

confidence: 99%

α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain

Shelukhina

Siniavin

Kasheverov

et al. 2023

IJMS

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Nicotinic acetylcholine receptors (nAChRs) present as many different subtypes in the nervous and immune systems, muscles and on the cells of other organs. In the immune system, inflammation is regulated via the vagus nerve through the activation of the non-neuronal α7 nAChR subtype, affecting the production of cytokines. The analgesic properties of α7 nAChR-selective compounds are mostly based on the activation of the cholinergic anti-inflammatory pathway. The molecular mechanism of neuropathic pain relief mediated by the inhibition of α9-containing nAChRs is not fully understood yet, but the role of immune factors in this process is becoming evident. To obtain appropriate drugs, a search of selective agonists, antagonists and modulators of α7- and α9-containing nAChRs is underway. The naturally occurring three-finger snake α-neurotoxins and mammalian Ly6/uPAR proteins, as well as neurotoxic peptides α-conotoxins, are not only sophisticated tools in research on nAChRs but are also considered as potential medicines. In particular, the inhibition of the α9-containing nAChRs by α-conotoxins may be a pathway to alleviate neuropathic pain. nAChRs are involved in the inflammation processes during AIDS and other viral infections; thus they can also be means used in drug design. In this review, we discuss the role of α7- and α9-containing nAChRs in the immune processes and in pain.

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Immunization with 674–685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice

Cited by 9 publications

References 28 publications

SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation

SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation

‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA

α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain

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