Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a recent worldwide coronavirus disease-2019 (COVID-19) pandemic. SARS-CoV-2 primarily causes an acute respiratory infection but can progress into significant neurological complications in some. Moreover, patients with severe acute COVID-19 could develop debilitating long-term sequela. Long-COVID is characterized by chronic symptoms that persist months after the initial infection. Common complaints are fatigue, myalgias, depression, anxiety, and “brain fog,” or cognitive and memory impairments. A recent study demonstrated that a mild COVID-19 respiratory infection could generate elevated proinflammatory cytokines and chemokines in the cerebral spinal fluid. This commentary discusses findings from this study, demonstrating that even a mild respiratory SARS-CoV-2 infection can cause considerable neuroinflammation with microglial and macrophage reactivity. Such changes could also be gleaned by measuring chemokines and cytokines in the circulating blood. Moreover, neuroinflammation caused by mild SARS-CoV-2 infection can also impair hippocampal neurogenesis, deplete oligodendrocytes, and decrease myelinated axons. All these changes likely contribute to cognitive deficits in long-COVID syndrome. Therefore, strategies capable of restraining neuroinflammation, maintaining better hippocampal neurogenesis, and preserving oligodendrocyte lineage differentiation and maturation may prevent or reduce the incidence of long-COVID after SARS-CoV-2 respiratory infection.

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

“…Neuroinflammation is an important pathogenesis of PD, and we show that Akk has anti-inflammatory effects in both the striatum and hippocampus; specifically, in these brain regions, Akk treatment significantly reduced the expression of astroglia-specific marker (GFAP) and microglia-specific marker (Iba-1). Hippocampal dentate granule cells in PD patients show abnormal morphogenesis and changes in the expression of differentiation markers [ 49 ], and neuroinflammation has been shown to alter adult neurogenesis [ 18 , 50 , 51 ]. Here, we show that Akk attenuates neuroinflammation in PD mice and increases the expression of DCX and SOX2 markers in the mouse hippocampus DG region, so we reasonably speculate that the improvement of neuroinflammation may be the reason why Akk promotes neurogenesis.…”

Microglia influence immune responses and restrict neurologic disease in response to central nervous system infection by a neurotropic murine coronavirus

“…In addition, evidence of neuronal degeneration and changes in glial cell morphology are also present in some hippocampal tissues derived from COVID-19 patients (Bayat et al, 2022). As indicated above, microglia have been shown to have distinct roles in host defense and disease in response to infection of the murine CNS with JHMV; similarly, microglia are suspected to have some role in neurologic manifestations associated with COVID-19 as well as long COVID (also called Post-Acute Sequelae of COVID, PASC) (Schwabenland et al, 2021;Albornoz et al, 2022;Jeong et al, 2022;Monje and Iwasaki, 2022;Strong, 2023;Thaweethai et al, 2023;Wei et al, 2023). Moreover, animal models of SARS-CoV-2 infection have demonstrated microglial activation and a role in the expression of cytokines/chemokines associated with neuroinflammation (Munoz-Fontela et al, 2020;Amruta et al, 2022;Olivarria et al, 2022).…”