Does COVID-19 contribute to development of neurological disease?

Background: Although coronavirus disease 2019 (COVID-19) has been associated primarily with pneumonia, recent data show that the causative agent of COVID-19, the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect a large number of vital organs beyond the lungs, such as the heart, kidneys, and the brain. Thus, there is evidence showing possible retrograde transmission of the virus from the olfactory epithelium to regions of the brain stem. Methods: This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on COVID-19 repercussion on the central nervous system (CNS). Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results: The angiotensin-converting enzyme 2 (ACE2) receptors being the receptor for the virus, the threat to the central nervous system is expected. Neurons and glial cells express ACE2 receptors in the CNS, and recent studies suggest that activated glial cells contribute to neuroinflammation and the devastating effects of SARS-CoV-2 infection on the CNS. The SARS-CoV-2-induced immune-mediated demyelinating disease, cerebrovascular damage, neurodegeneration, and depression are some of the neurological complications discussed here. Conclusion: This review correlates present clinical manifestations of COVID-19 patients with possible neurological consequences in the future, thus preparing healthcare providers for possible future consequences of COVID-19

Sleep Deprivation and Neurological Disorders

Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin proteins like α-synuclein, amyloid-β, and tau which are involved in major neurodegenerative diseases like Alzheimer\u27s disease and Parkinson\u27s disease. In addition, SD is also shown to affect the glymphatic system, a glial-dependent metabolic waste clearance pathway, causing accumulation of misfolded faulty proteins in synaptic compartments resulting in cognitive decline. Also, SD affects the immunological and redox system resulting in neuroinflammation and oxidative stress. Hence, it is important to understand the molecular and biochemical alterations that are the causative factors leading to these pathophysiological effects on the neuronal system. This review is an attempt in this direction. It provides up-to-date information on the alterations in the key processes, pathways, and proteins that are negatively affected by SD and become reasons for neurological disorders over a prolonged period of time, if left unattended

Sleep deprivation and neurological disorders

Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin proteins like α-synuclein, amyloid-β, and tau which are involved in major neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. In addition, SD is also shown to affect the glymphatic system, a glial-dependent metabolic waste clearance pathway, causing accumulation of misfolded faulty proteins in synaptic compartments resulting in cognitive decline. Also, SD affects the immunological and redox system resulting in neuroinflammation and oxidative stress. Hence, it is important to understand the molecular and biochemical alterations that are the causative factors leading to these pathophysiological effects on the neuronal system. This review is an attempt in this direction. It provides up-to-date information on the alterations in the key processes, pathways, and proteins that are negatively affected by SD and become reasons for neurological disorders over a prolonged period of time, if left unattended

Telmisartan Protects Mitochondrial Function, Gait, and Neuronal Apoptosis by Activating the Akt/GSK3β/PGC1α Pathway in an MPTP-Induced Mouse Model of Parkinson's Disease

Background: Mitochondrial dysfunction is one of the major hallmarks of Parkinson’s disease (PD). Recently, angiotensin II type 1 and type 2 receptors (AT1R, AT2R) were reported to be present on the mitochondrial membrane. Both are crucial players in the brain renin-angiotensin system (RAS). Current evidence indicates that blockade of brain AT1R protects dopaminergic neurons in PD. Methods: Thus, the current study was aimed to explore the effects of Telmisartan (Tel), a selective AT1R blocker, on mitochondrial function and a mouse model by exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [250 mg/kg body weight (10 divided i.p. injections, each 25 mg/kg body weight at 3.5 days interval) + Probenecid 250 mg/kg]. Gait function was assessed by beam walk, and mice were euthanized on the 35th day and their brain tissues isolated for Western blot analysis. Results: Pretreatment with Tel significantly protected motor functions during the beam walk in MPTP-treated mice. Tel attenuated the increased levels of AT1R, α-syn, and inflammatory markers such as inducible nitric oxide synthase (iNOS) and ionized calcium-binding adaptor molecule 1 (IBA1) in MPTP-treated mice. In addition, Tel preserved the expression of AT2R, tyrosine hydroxylase (TH), p-Akt/Akt, and p-GSK3β (Ser-9)/GSK3β, as well as protecting mitofusin protein 1 (MFN1) and Peroxisome proliferator-activated receptor-gamma coactivator-α (PGC1α), a critical activator of mitochondrial biogenesis. Conclusion: These results indicate that Tel protects mitochondrial function and gait in a mouse model of PD by modulating the Akt/GSK3β/PGC1α pathway

“Janus-Faced” α-Synuclein: Role in Parkinson’s Disease

International audienc

Does COVID-19 contribute to development of neurological disease?

Background: Although coronavirus disease 2019 (COVID-19) has been associated primarily with pneumonia, recent data show that the causative agent of COVID-19, the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect a large number of vital organs beyond the lungs, such as the heart, kidneys, and the brain. Thus, there is evidence showing possible retrograde transmission of the virus from the olfactory epithelium to regions of the brain stem. Methods: This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on COVID-19 repercussion on the central nervous system (CNS). Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results: The angiotensin-converting enzyme 2 (ACE2) receptors being the receptor for the virus, the threat to the central nervous system is expected. Neurons and glial cells express ACE2 receptors in the CNS, and recent studies suggest that activated glial cells contribute to neuroinflammation and the devastating effects of SARS-CoV-2 infection on the CNS. The SARS-CoV-2-induced immune-mediated demyelinating disease, cerebrovascular damage, neurodegeneration, and depression are some of the neurological complications discussed here. Conclusion: This review correlates present clinical manifestations of COVID-19 patients with possible neurological consequences in the future, thus preparing healthcare providers for possible future consequences of COVID-19

SLEEP, BRAIN VASCULAR HEALTH AND AGEING

Sleep maintains the function of the entire body through homeostasis. Chronic sleep deprivation (CSD) is a prime health concern in the modern world. Previous reports have shown that CSD has profound negative effects on brain vasculature at both the cellular and molecular levels, and that this is a major cause of cognitive dysfunction and early vascular ageing. However, correlations among sleep deprivation (SD), brain vascular changes and ageing have barely been looked into. This review attempts to correlate the alterations in the levels of major neurotransmitters (acetylcholine, adrenaline, GABA and glutamate) and signalling molecules (Sirt1, PGC1α, FOXO, P66shc, PARP1) in SD and changes in brain vasculature, cognitive dysfunction and early ageing. It also aims to connect SD-induced loss in the number of dendritic spines and their effects on alterations in synaptic plasticity, cognitive disabilities and early vascular ageing based on data available in scientific literature. To the best of our knowledge, this is the first article providing a pathophysiological basis to link SD to brain vascular ageing

Mitochondrial and Organellar Crosstalk in Parkinson’s Disease

Mitochondrial dysfunction is a well-established pathological event in Parkinson’s disease (PD). Proteins misfolding and its impaired cellular clearance due to altered autophagy/mitophagy/pexophagy contribute to PD progression. It has been shown that mitochondria have contact sites with endoplasmic reticulum (ER), peroxisomes and lysosomes that are involved in regulating various physiological processes. In pathological conditions, the crosstalk at the contact sites initiates alterations in intracellular vesicular transport, calcium homeostasis and causes activation of proteases, protein misfolding and impairment of autophagy. Apart from the well-reported molecular changes like mitochondrial dysfunction, impaired autophagy/mitophagy and oxidative stress in PD, here we have summarized the recent scientific reports to provide the mechanistic insights on the altered communications between ER, peroxisomes, and lysosomes at mitochondrial contact sites. Furthermore, the manuscript elaborates on the contributions of mitochondrial contact sites and organelles dysfunction to the pathogenesis of PD and suggests potential therapeutic targets

Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus–pituitary–adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut–brain axis (GBA) for the effective management of depressive behavior and anxiety

Does COVID-19 contribute to development of neurological disease?

Background: Although coronavirus disease 2019 (COVID-19) has been associated primarily with pneumonia, recent data show that the causative agent of COVID-19, the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect a large number of vital organs beyond the lungs, such as the heart, kidneys, and the brain. Thus, there is evidence showing possible retrograde transmission of the virus from the olfactory epithelium to regions of the brain stem. Methods: This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on COVID-19 repercussion on the central nervous system (CNS). Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. Results: The angiotensin-converting enzyme 2 (ACE2) receptors being the receptor for the virus, the threat to the central nervous system is expected. Neurons and glial cells express ACE2 receptors in the CNS, and recent studies suggest that activated glial cells contribute to neuroinflammation and the devastating effects of SARS-CoV-2 infection on the CNS. The SARS-CoV-2-induced immune-mediated demyelinating disease, cerebrovascular damage, neurodegeneration, and depression are some of the neurological complications discussed here. Conclusion: This review correlates present clinical manifestations of COVID-19 patients with possible neurological consequences in the future, thus preparing healthcare providers for possible future consequences of COVID-19