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

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.

Complications of COVID-19 on the Central Nervous System: Mechanisms and Potential Treatment for Easing Long COVID.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades human cells by binding to the angiotensin-converting-enzyme-2 (ACE-2) using a spike protein and leads to Coronavirus disease-2019 (COVID-19). COVID-19 primarily causes a respiratory infection that can lead to severe systemic inflammation. It is also common for some patients to develop significant neurological and psychiatric symptoms. The spread of SARS-CoV-2 to the CNS likely occurs through several pathways. Once spread in the CNS, many acute symptoms emerge, and such infections could also transpire into severe neurological complications, including encephalitis or ischemic stroke. After recovery from the acute infection, a significant percentage of patients develop "long COVID," a condition in which several symptoms of COVID-19 persist for prolonged periods. This review aims to discuss acute and chronic neurological problems after SARS-CoV-2 infection. The potential mechanisms by which SARS-CoV-2 enters the CNS and causes neuroinflammation, neuropathological changes observed in post-mortem brains of COVID-19 patients, and cognitive and mood problems in COVID-19 survivors are discussed in the initial part. The later part of the review deliberates the causes of long COVID, approaches for noninvasive tracking of neuroinflammation in long COVID patients, and the potential therapeutic strategies that could ease enduring CNS symptoms observed in long COVID.

Can mild cognitive impairment and Alzheimer's disease be diagnosed by monitoring a miRNA triad in the blood?

Objectively diagnosing age-related cognitive impairment (ACI), mild cognitive impairment (MCI), and early-stage Alzheimer's disease (AD) is a difficult task, as most cognitive impairment is clinically established via questionnaires, history, and physical examinations. A recent study has suggested that monitoring a miRNA triad, miR-181a-5p, miR-146a-5p, and miR-148a-3p can identify ACI and its progression to MCI and AD (Islam et al., EMBO Mol Med. 13: e14997, 2021). This commentary deliberates findings from this article, such as elevated levels of the miRNA triad in the brain impairing neural plasticity and cognitive function, the efficiency of measuring the miRNA triad in the circulating blood diagnosing MCI and AD, and the promise for improving cognitive function in MCI and AD by inhibiting this miRNA triad. Additional studies required prior to employing this miRNA triad in clinical practice are also discussed.

Treating Parkinson's disease by astrocyte reprogramming: Progress and challenges.

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is typified by both motor and nonmotor symptoms. The current medications provide symptomatic relief but do not stimulate the production of new dopaminergic neurons in the substantia nigra. Astrocyte reprogramming has recently received much attention as an avenue for increasing functional dopaminergic neurons in the mouse PD brain. By targeting a microRNA (miRNA) loop, astrocytes in the mouse brain could be reprogrammed into functional dopaminergic neurons. Such in vivo astrocyte reprogramming in the mouse model of PD has successfully added new dopaminergic neurons to the substantia nigra and increased dopamine levels associated with axonal projections into the striatum. This review deliberates the astrocyte reprogramming methods using specific transcription factors and mRNAs and the progress in generating dopaminergic neurons in vivo. In addition, the translational potential, challenges, and potential risks of astrocyte reprogramming for an enduring alleviation of parkinsonian symptoms are conferred.