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

ESLICARBAZEPINE AND MEMORY IMPAIRMENT IN TEMPORAL LOBE EPILEPSY: A STUDY ON THE ATTENUATING EFFECT OF NEFIRACETAM

Objectives: The objectives of the present investigation were to evaluate the memory impairment (MI) activity of eslicarbazepine (ESL) in temporal lobe epilepsy (TLE) at a normal and reduced dose, to evaluate the possible protective effect of nefiracetam (NEF) on MI induced by ESL at a normal and reduced dose, and to evaluate the antiepileptic activity of ESL on TLE in the presence and absence of NEF. Methods: MI activity was evaluated by Barnes maze (BM) on lithium-pilocarpine-induced TLE in Wistar albino rats. Rats were trained by releasing from the portable start-up box after keeping sometimes inside, to find the fixed dark escape hole of BM. Mild aversive light overhead was used to motivate the finding. Animals failed to do so were guided manually. Trained animals were taken for the study and checked the escape latency time (ELT) and the error scores (error entry). The treatment was given for 1 month and MI activity was measured on every 7th day and antiepileptic activity on every 8th day. Phenytoin was used as standard antiepileptic drug (AED) to compare the MI extent of ESL. Results: ESL-treated group animals had shown increased ELT and error scores, on comparison with control group, implying the MI as a result treatment of the AED ESL. MI was dose dependent and shown decreased MI in animals treated with half dose of ESL. When NEF was administered with the ESL significantly decreased the MI as well as showed potent anticonvulsant activity when compared to control and ESL alone treated group. The levels of acetylcholinesterase (AChE) in ESL group were observed to be increased against control group. Cotreatment of NEF results in decreased levels of AChE on comparison with control and the group treated with ESL. Conclusion: The reduced dose of ESL and NEF combination was found to have synergized the protecting effect against MI compared to normal ESL and NEF group without altering anticonvulsant activity. However, further studies are required to elicit detailed protective activity of NEF on MI induced by ESL

Effects of Feeding Anti-Stressor and Immunizer to Broiler Chickens on Growth Performance, Meat Yield and Immunity

To examine the influence of anti-stressor and immunizer on the growth of broiler chickens, their meat yield features, and immune response, a total of 360 Cobb-500 day-old commercial broiler chicks were used in a 35-day feeding trial. Experimental birds were randomly assigned to three dietary treatments having six replications each of 20 birds. During the starter and grower periods, corn-soya-based plant protein mash diets were provided. Starter and grower diets were provided in two phases: day-old to 21 days and 22-35 days, respectively. The first group of chicks was treated as control (diet 1), the second group was offered a control diet supplemented with an anti-stressor (diet 2) and the third group received a control diet to which an immunizer was incorporated (diet 3). Growth performance data were recorded weekly. Meat yield traits were determined and blood samples were collected on termination of the experiment. Data were subjected to analysis of variance (ANOVA) in a completely randomized design (CRD). Results showed that significantly higher body weight and lowest FCR values were found in the anti-stressor incorporated group (P [J Bangladesh Agril Univ 2022; 20(2.000): 167-174

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

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

International audienc

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

Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle

The human microbiota comprises trillions of symbiotic microorganisms and is involved in regulating gastrointestinal (GI), immune, nervous system and metabolic homeostasis. Recent observations suggest a bidirectional communication between the gut microbiota and the brain via immune, circulatory and neural pathways, termed the Gut-Brain Axis (GBA). Alterations in gut microbiota composition, such as seen with an increased number of pathobionts and a decreased number of symbionts, termed gut dysbiosis or microbial intestinal dysbiosis, plays a prominent role in the pathogenesis of central nervous system (CNS)-related disorders. Clinical reports confirm that GI symptoms often precede neurological symptoms several years before the development of neurodegenerative diseases (NDDs). Pathologically, gut dysbiosis disrupts the integrity of the intestinal barrier leading to ingress of pathobionts and toxic metabolites into the systemic circulation causing GBA dysregulation. Subsequently, chronic neuroinflammation via dysregulated immune activation triggers the accumulation of neurotoxic misfolded proteins in and around CNS cells resulting in neuronal death. Emerging evidence links gut dysbiosis to the aggravation and/or spread of proteinopathies from the peripheral nervous system to the CNS and defective autophagy-mediated proteinopathies. This review summarizes the current understanding of the role of gut microbiota in NDDs, and highlights a vicious cycle of gut dysbiosis, immune-mediated chronic neuroinflammation, impaired autophagy and proteinopathies, which contributes to the development of neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington’s disease, multiple sclerosis, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We also discuss novel therapeutic strategies targeting the modulation of gut dysbiosis through prebiotics, probiotics, synbiotics or dietary interventions, and faecal microbial transplantation (FMT) in the management of NDDs

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