Neurotropic Properties Research Articles

NEUROTROPIC EFFECTS OF ENDOGENOUS COMPOUNDS – TYRONOME COMPONENTS IN THE CENTRAL NERVOUS SYSTEM

Background. During the last decades, data on potential cytoprotective effects of decarboxylated and deiodinated endogenous compounds – metabolites of thyroid hormones, constituting the thyronome, have been accumulated. The aim of this review is to systematize the biological effects of thyronome components in the central nervous system from the position of their possible role as potential neuroprotectants. Material and methods. English- and Russian-language full-text articles from PubMed, Mendeley, and e-library electronic databases were selected for analysis using query «(thyroid OR thyroid hormone metabolite OR *-iodo-thyronamine OR thyronamine OR TAAR OR thyronome OR T0AM OR T1AM OR thyroacetic acid) AND (brain OR central nervous system OR CNS OR stroke OR neurodegenerat*)». The search depth amounted to 10 years. Results. The review systematizes the most important neurotropic properties of 3-T1AM and other thyronome components, including their influence on behavioral effects, memory, pain threshold level, apoptosis, autophagy, and excitotoxic neuronal death, and describes the role of individual receptors and intracellular signal transduction pathways in the realization of these properties. Conclusion. The components of thyronome, in particular 3-T1AM, demonstrate a wide range of potential neuroprotective properties, and for its potential use in the clinic, it is relevant to find ways to increase local concentration in the brain or permeability to the BBB, as well as the development of more effective synthetic analogues.

Insights into the Phytochemical Profile and Therapeutical Potential of Withania Somnifera (L.) Dunal

Abstract: Withania somnifera (L.) Dunal (W. somnifera) is an herb commonly known by its English name Winter Cherry, and Ashwagandha in Hindi. It has been used as a traditional Rasayana herb for a long time. It is a rich reservoir of bioactive compounds known as withanolides, namely, withaferin-A and withanolide-D. Its current research covers many aspects of human health, which include anti-stress, anti-tumor, 9immuno-modulatory, hypocholesterolemic, hepatoprotective, hypoglycemic, diuretic, anti-convulsant, neurotropic, adaptogenic, and cardioprotective properties. This overview W. somnifera traditional uses, phytochemical, and pharmacological activities. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.

The host cells suppress the proliferation of pseudorabies virus by regulating the PI3K/Akt/mTOR pathway.

PRV, known for its neurotropic properties, is capable of inducing severe neuronal damage. Our study discovered that following PRV infection, the expression of MMP2 was upregulated, leading to the degradation of ZO-1. Furthermore, upon PRV infection in the host, the promoter of TIMP1 is significantly activated, resulting in a significant increase in TIMP1 protein levels. This upregulation of TIMP1 inhibits the proliferation of PRV through the PI3K/Akt signaling pathway. This study elucidated the mechanism through which PRV, including the PRV XJ delgE/gI/TK strains, compromises the blood-brain barrier and identifies the antiviral response characterized by the activation of the PI3K/Akt signaling pathway within infected host cells. These findings provide potential therapeutic targets for the clinical management and treatment of PRV.

Purchasing “Nootropics” Online: Identification and Quantification of Ingredients in Phenibut-Containing Products

Background and Objectives: Phenibut is a central nervous system drug that is registered and used in clinical practice as a prescription medication. In recent decades, the drug has become popular as a “nootropic and cognition enhancer” because of its active marketing as a dietary or food supplement sold online. This has resulted in a growing number of case reports on acute toxicity and withdrawal symptoms and has raised concerns about the quality of phenibut-containing products. Materials and Methods: We used high-performance liquid chromatography with diode-array detection and ultra-performance liquid chromatography–mass spectrometry to investigate the quality of six phenibut-containing samples purchased from three internet suppliers. Results: Substantially lower levels of the active pharmaceutical ingredient than claimed on the packaging were found for three of the supplements tested. A considerably higher level of phenibut was present in one product. All online-purchased phenibut-containing capsules included declared and undeclared ingredients found in various dietary supplements claiming to have metabolic, neurotropic, antioxidant, anti-inflammatory, and neuroprotective properties. Conclusions: The online-purchased phenibut products contained undeclared ingredients and the content of phenibut differed from the declared. The combinations of these additional ingredients with phenibut have not been tested for activity or safety and their use warrants further attention to avoid potential health problems.

H7N7 viral infection elicits pronounced, sex-specific neuroinflammatory responses in vitro.

Influenza A virus (IAV) infection can increase the risk of neuroinflammation, and subsequent neurodegenerative diseases. Certain IAV strains, such as avian H7N7 subtype, possess neurotropic properties, enabling them to directly invade the brain parenchyma and infect neurons and glia cells. Host sex significantly influences the severity of IAV infections. Studies indicate that females of the reproductive age exhibit stronger innate and adaptive immune responses to IAVs compared to males. This heightened immune response correlates with increased morbidity and mortality, and potential neuronal damage in females. Understanding the sex-specific neurotropism of IAV and associated mechanisms leading to adverse neurological outcomes is essential. Our study reveals that primary hippocampal cultures from female mice show heightened interferon-β and pro-inflammatory chemokine secretion following neurotropic IAV infection. We observed sex-specific differences in microglia activation: both sexes showed a transition into a hyper-ramified state, but only male-derived microglia exhibited an increase in amoeboid-shaped cells. These disparities extended to alterations in neuronal morphology. Neurons derived from female mice displayed increased spine density within 24 h post-infection, while no significant change was observed in male cultures. This aligns with sex-specific differences in microglial synaptic pruning. Data suggest that amoeboid-shaped microglia preferentially target postsynaptic terminals, potentially reducing neuronal hyperexcitability. Conversely, hyper-ramified microglia may focus on presynaptic terminals, potentially limiting viral spread. In conclusion, our findings underscore the utility of primary hippocampal cultures, incorporating microglia, as an effective model to study sex-specific, virus-induced effects on brain-resident cells.

The Theoretical Substantiation of the Targeted Search for New DPP4 Inhibitors. Computational Studies of Potential Candidates

Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, in addition to their role in improving glycemic control, help to reduce endothelial dysfunction and have hypolipidemic, anti-atherosclerotic, antitumor, antiviral, and neurotropic properties. This multi-target property may be one of the reasons for repurposing therapeutic treatment strategies with existing agents and the basis for finding new agents to inhibit this target. Based on the structural prerequisites and the evolutionary path of creating DPP4 inhibitors, an inhibitory (R)-β-aminoamide base was used as the basis for constructing potential candidates. It contained a substituted piperazine-2-one derivative and (S)-pyrrolidine-2-carbonitrile fragment, as well as phenyl and diphenyl rings, which were additionally saturated with substituents of various electronic structures, in position 4 of the β-aminoamide chain. The construction of the molecules was carried out taking into account the correspondence of chiral centers to combinations of chiral chains at the DPP4 binding site to possibly prevent a decrease in the inhibitory activity. In silico assessment of the “drug-likeness” and pharmacokinetic profile of the group of compounds studied showed that it had favorable characteristics and could be recommended for further molecular docking in order to predict the likely inhibition of the catalytic activity of DPP4. According to the results of docking, molecules with a moderate and high affinity were found. A detailed analysis of the resulting complexes showed that only nine compounds had a binding mode similar to classical inhibitors. According to the calculated array of values and analysis of the results of docking among the derivatives tested, a hit compound was found as a promising DPP4 inhibitor.

Molecular Docking of Fisetin as a Multi-target drug in the treatment of Alzheimer’s disease

Alzheimer’s disease is a slow deadly form of dementia occurring in almost 70% of the older generation. Throughout the world, there are approximately 47 million people affected. Countries that are mostly affected by Alzheimer’s disease with the highest are Turkey and Lebanon by 57% and 56% respectively. The lowest rates include India, Cambodia, Georgia, and Singapore. This includes symptoms such as disorientation, mood swings, behavioral issues, etc. ultimately leading to death. The primitive appearance of the alpha-beta plaques and neurofibrillary tangles in the different regions of the brain leads to the cause of AD progression. In this present study, Fisetin which is a plant flavonoid having neurotropic and neuroprotective properties is docked with the drug targets of Alzheimer’s disease. The study was focused on analysing the molecular interaction of Fisetin with potential drug targets of Alzheimer’s disease. The docking was performed using AutoDock 4.2. The minimum binding energy studies explain the efficiency of the ligand binding with the therapeutic target proteins. Proteins play a significant role in Alzheimer’s disease as it is responsible for various functions which also are the major attributes of Alzheimer's disease namely amyloid-β production, tau phosphorylation, synaptic function, neurogenesis, and memory which all are influenced by dysregulation of this enzyme. Four proteins were selected based on the action and function they play in the progression of Alzheimer’s disease namely FYN tyrosine kinase, Beta Secretase (BACE 1), Gamma secretase, and Glycogen synthase kinase 3-beta (GSK3-β). The minimum binding energy scores for the following 3D molecular structures were FYN tyrosine kinase = -8.2 kcal/mol, BACE1= -10.67kcal/mol, Gamma secretase = - 10.03kcal/mol, GSK3 Beta = -10.47kcal/mol; No. of hydrogen bonds: 12, 10, 10 and 21 respectively. From the 4 potential Alzheimer’s drug targets, Glycogen synthase kinase 3-beta (GSK3-β) and Beta Secretase, had the best interaction with Fisetin with the lowest binding energy. Along with this Fisetin was analyzed for its molecular properties, drug-likeness, biological activity, and toxicity using the Way2drug bio tool.

Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders

The lack of effective treatments for neurodegenerative diseases (NDs) is an important current concern. Lipid nanoparticles can deliver innovative combinations of active molecules to target the various mechanisms of neurodegeneration. A significant challenge in delivering drugs to the brain for ND treatment is associated with the blood–brain barrier, which limits the effectiveness of conventional drug administration. Current strategies utilizing lipid nanoparticles and cell-penetrating peptides, characterized by various uptake mechanisms, have the potential to extend the residence time and bioavailability of encapsulated drugs. Additionally, bioactive molecules with neurotropic or neuroprotective properties can be delivered to potentially mediate the ND targeting pathways, e.g., neurotrophin deficiency, impaired lipid metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, accumulation of misfolded proteins or peptide fragments, toxic protein aggregates, oxidative stress damage, and neuroinflammation. This review discusses recent advancements in lipid nanoparticles and CPPs in view of the integration of these two approaches into nanomedicine development and dual-targeted nanoparticulate systems for brain delivery in neurodegenerative disorders.

Development of Zika Virus E Variants for Pseudotyping Retroviral Vectors Targeting Glioblastoma Cells.

A fundamental idea for targeting glioblastoma cells is to exploit the neurotropic properties of Zika virus (ZIKV) through its two outer envelope proteins, prM and E. This study aimed to develop envelope glycoproteins for pseudotyping retroviral vectors that can be used for efficient tumor cell infection. Firstly, the retroviral vector pNLlucAM was packaged using wild-type ZIKV E to generate an E-HIVluc pseudotype. E-HIVluc infection rates for tumor cells were higher than those of normal prME pseudotyped particles and the traditionally used vesicular stomatitis virus G (VSV-G) pseudotypes, indicating that protein E alone was sufficient for the formation of infectious pseudotyped particles. Secondly, two envelope chimeras, E41.1 and E41.2, with the E wild-type transmembrane domain replaced by the gp41 transmembrane and cytoplasmic domains, were constructed; pNLlucAM or pNLgfpAM packaged with E41.1 or E41.2 constructs showed infectivity for tumor cells, with the highest rates observed for E41.2. This envelope construct can be used not only as a tool to further develop oncolytic pseudotyped viruses for therapy, but also as a new research tool to study changes in tumor cells after the transfer of genes that might have therapeutic potential.

SYNTHESIS AND PROPERTIES OF NEW 1-HYDRAZINOCARBONYLMETHYL-7-BROMO-5-PHENYL-3-ARYLYDENE-1,2-DIHYDRO-3H-1,4-BENZODIAZEPIN-2-ONES

It is known that 1,4-benzodiazepines have neurotropic properties. Previously, we synthesized a series of 3-arylidene-1,2-dihydro-3H-1,4-benzdiazepin-2-ones 11-18 and showed that they exhibit significant analgesic activity. They also show significant affinity for central benzodiazepine receptors and TSPO receptors CNS. With this in mind, we have previously modified the series of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones by alkylation of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with monobromoacetic acid methyl ester to the first position of the 1,4-diazepine ring to obtain 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26, which showed pronounced analgesic activity. The aim of this work is to synthesize and study the affinity for CBR and TSPO receptors 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 27-31, which have not been previously described in the literature. Compounds 27-31 were synthesized as a result of the reaction of 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26 with hydrazine hydrate while stirring the components in ethanol. The yields of the reaction products were 65-92%. It was shown that the hydrazinolysis technique used provides high yields of the target compounds. The structure of the synthesized compounds was confirmed by mass spectrometry and 1H NMR spectroscopy. The affinity of the synthesized compounds to the central benzodiazepine receptors CNS (CBR) and TSPO receptors CNS was studied. The affinity of compounds 27-31 was determined in vitro by radioligand analysis by their ability to displace the commercial radioligands [3H] flumazenil and [3H]PK11195 from their specific binding sites in the GABAA receptor complex and TSPO receptors of the synaptic and the mitochondrial fractions of the rat brain membranes, respectively. Compound 27 displaces the commercial [3H]flumazenil radioligand from its specific binding sites in the GABAA receptor complex by 80.1%, and simultaneously exhibits a very low affinity for TSPO receptors. Derivative 27 is the most potent CBR ligand among the investigated compounds and it is a promising compound for pharmacological research. It has been established that in the synthesized series of 3-fluorobenzylidene derivatives, varying the position of the fluorine atom in the benzylidene fragment leads to change affinity for TSPO receptors. It has been established that the para- position of the fluorine atom in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule is the most important descriptor that determines their affinity for the TSPO receptors. These data agree with the data available in the literature on the effect of the position of chlorine and bromine atoms in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule on the affinity for the TSPO receptors. It was found that the main structural fragment that determines the affinity of binding of 3-benzylidene derivatives to TSPO receptors is the presence of electronegative substituents in the para-position of the benzylidene fragment: para–Hal>>оrtho–Hal>meta–Hal (affinity for TSPO) (Hal= Br, F) Thus, the expediency of further study of this class of compounds is shown.

Neurotropic properties of high- and low-selective sodium-glucose cotransporter type 2 inhibitors in type 2 diabetic patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Methods: We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Results: The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue; this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue; ciliated cells and goblet cells in bronchial tissue; and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion: Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood–brain barrier via pericytes. Additionally, SARS-CoV-2–induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.

The internal ribosome entry site determines the neurotropic potential of enterovirus A71

The mechanisms underlying tissue-specific replication of enteroviruses are currently unclear. Although enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are both common pathogens that cause hand-foot-mouth disease, they display quite different neurotropic properties. Herein, we characterized the role of the internal ribosome entry site (IRES) in determining neurovirulence using an oral inoculation model of EV-A71. The receptor transgenic (hSCARB2-Tg) mice developed neurological symptoms after being infected with a mouse-adapted EV-A71 strain (MP4) via different administrative routes. Intragastric administration of the MP4 strain caused pathological changes such as neuronal loss and neuropil vacuolation, whereas replacing EV-A71 IRES with CV-A16 abolished the neuropathological phenotypes. The attenuated neurotropic potential of IRES-swapped EV-A71 was observed even in mice that received intraperitoneal and intracerebral inoculations. Fewer chimeric MP4 viral RNAs and proteins were detected in the mouse tissues, regardless of the inoculation route. Tissue-specific replication can be reflected in cell-based characterization. While chimeric MP4 virus replicated poorly in human intestinal C2BBe1 and neuroblastoma SH-SY5Y cells, its replication in susceptible rhabdomyosarcoma cells was not affected. Overall, our results demonstrated that the IRES determined the neurotropic potential of EV-A71 and CV-A16, emphasizing the importance of the IRES in tissue tropism, along with the host receptors.

Hearing screening test in neonates born to COVID-19-positive mothers.

Infection with COVID-19 during pregnancy was not a risk factor for hearing loss, similar to other studies. • The pathogenetic mechanism of the viral-induced impairment of the organ of Corti includes direct damage to the hair cells and indirect damage due to the induction of the innate inflammatory response. • Early data suggested that the SARS-CoV-2 virus also has neurotropic properties with manifestations from the sensory epithelia. • Although the intrauterine infection remains controversial, the expression of the ACE-2 receptor on the placenta and the detection of IgM antibodies, as well as the covid-19 genome in fetuses, make the vertical transmission tenable. • In our study, the newborn hearing screening results indicate that COVID-19 infection during pregnancy is not a risk factor for hearing loss.

Diagnostic Value of Erythropoietin Levels in Umbilical Cord Blood in Hypoxic-Ischemic Brain Injury: Clinical Observational Cross-Sectional Study

Background. In recent years erythropoietin has received particular attention due to the discovery of its important non-haematological effects. Erythropoietin is recognized as a pluripotent glycoprotein, manifesting neurotropic and neuroprotective properties as well as participating in angio-, neuro- and oligodendrogenesis, interferes with the effects of hypoxia-ischemia, oxidative stress and associated with them inflammation and apoptosis in the brain. During fetal hypoxia, the dominant production of erythropoietin switches to the placenta, starting its active synthesis to protect the brain, heart and other vital organs from harmful effects of severe hypoxia.Objectives. The study was aimed at determining the correlation between the severity of hypoxic ischemic brain injury and erythropoietin level in the artery and vein of the umbilical cord.Methods. A clinical observational cross-sectional study was conducted on the basis of the Maternity Hospital, Neonatal Pathology and Pediatric Departments №1 and №2 of the Research Institute of Obstetrics and Pediatrics under the auspices of Rostov State Medical University, Russian Federation. The study included 184 newborns with moderate (group II, n = 78) and severe hypoxic ischemic injury of the central nervous system (group III, n = 42). Group I consisted of 64 children without signs of central nervous system injury in the early neonatal period. Among which, following the maternal medical histories, 40 newborns were allocated to the group with the apparent development of delayed manifestation of neurological pathology. The evaluation of erythropoietin concentration in the umbilical cord blood was conducted separately in the artery and vein with Erythropoietin-EIA-BEST, a set of reagents for the enzyme-linked determination of erythropoietin concentration in the blood serum. Statistical analysis was carried out via MS Excel 2019 (Microsoft, USA), Statistica 12.5, (IBM, USA), SPSS27.001.Results. Erythropoietin concentrations in the blood of the artery and vein of the umbilical cord in the groups of newborns were determined according to the severity of hypoxic-ischemic brain injury. The authors of the study showed the correlation between the “maternal-placental-fetal” blood flow at 36–40 weeks of gestation, which parameters are important antenatal predictors of the central nervous system injury, and the values of erythropoietin in arterial and venous umbilical cord blood as diagnostic markers.Conclusion. The severity of cerebral abnormalities is determined by a high level of erythropoietin, while a decrease in erythropoietin level with severe cerebral deficit can mark a disabling injury.

Vestibular neuronitis in a child with coronavirus disease 2019 infection and review of the literature.

This article presents the case of an adolescent with asymptomatic coronavirus disease 2019 infection who had vestibular neuronitis symptoms. The new coronavirus disease 2019 demonstrates neurotropic properties, apart from airway symptoms. Early in the pandemic, coronavirus disease 2019 infection had been associated with olfactory disturbances. Accumulative evidence supports that both the infection with coronavirus disease 2019 and the vaccination against the virus may induce a condition of vestibular hypofunction, known as vestibular neuronitis. Coronavirus disease 2019 may directly affect the vestibular organs and ganglia, or indirectly damage them via immune-mediated mechanisms. In most cases, complete recovery is achieved with the typical therapeutic approaches for vestibular neuronitis, consisting of supportive measures and corticosteroids. Physicians may expect an increased incidence of vestibular neuronitis during the coronavirus disease 2019 pandemic. Conversely, coronavirus disease 2019 infection should be considered in patients with sudden vestibular symptoms.

Dimethyloxobutylphosphonyl dimethylate (dimephosphone). Pharmacological effects. Neurotropic and cerebroprotective properties

Dimethyloxobutylphosphonyl dimethylate (dimephosphone) is a Russian drug of metabolic action, developed in Kazan in 1952 at the Institute of Organic and Physical Chemistry named after A. E. Arbuzov, Kazan Branch of the Academy of Sciences of the USSR, and at the Department of Pharmacology, Kazan State Medical University. Its novelty and originality are confirmed by patents in many countries. [2] The paper presents a review of the literature, which confirms that dimephosphone is able to restore damaged brain structures, improves cerebral circulation, and has neurotropic and cerebroprotective properties.

ПОСТІНФЕКЦІЙНА, ВИКЛИКАНА COVID-19, ДЕМІЄЛІНІЗУЮЧА ХВОРОБА

SARS-COV-2 is a neurotropic virus that can trigger a large-scale outbreak of neurological complications in the future. SARS-COV-2 virus has neuroinvasive and neurotropic properties allow it to enter the central nervous system (CNS) and infect neurons, accumulate in nervous tissue and promote the development of delayed neurodegenerative processes. Among the neurological complications of SARS-CoV-2 to date, we can distinguish a group of demyelinating lesions of the CNS. The paper describes two cases of severe COVID-19, which were accompanied by neurological disorders and multifocal white matter lesions on MRI, which may correspond to demyelinating CNS disease. Both cases may be a manifestation of an acute infectious demyelinating process associated with COVID-19, as the clinical picture was appropriate, and neuroimaging showed multifocal lesions of the white matter. Other clinical signs confi rming this diagnosis were previously confi rmed acute viral COVID-19 infection and the absence of a history of demyelinating diseases such as multiple sclerosis in both patients. Monitoring such patients can help to understand better and identify factors in the early stages of the disease and to predict its progression. In the future, it will also allow the development of eff ective treatment strategies and the ability to reduce the risk of demyelinating process or its progression during SARS-CoV-2 infection.

The effect of the severity of COVID-19 on the sequelae of the audiovestibular system.

Objectives: The neurotropic and neuroinvasive properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been described. It remains unknown how SARS-CoV-2 affects the audiovestibular system when it causes mild or severe disease. In this study, the sequelae effect of SARS-CoV-2 on the audiovestibular systems of different patient groups was investigated using objective and subjective test batteries. Methods: In this present study, we evaluated vestibulocochlear functions of patients who previously had Coronavirus Disease-2019 (COVID-19) with pure tone audiometry, ocular vestibular-evoked myogenic potential (o-VEMP), and cervical vestibular-evoked myogenic potential (c-VEMP) tests to identify possible sequelae by comparing them with the control group. Results: We found that the amplitude of p13-n23 was lower in both groups of patients than in the control group (p < 0.001). In the results of the left ear c-VEMP, the amplitude of p13-n23 was statistically different between the outpatient, inpatient, and control groups. The amplitude of p13-n23 was lower in both groups of patients than in the control group (p < 0.001). In the evaluation of the o-VEMP in the left ear, we observed a statistically significant difference in the latency of n10 (p = 0.006) and the amplitude of n10-p15 (p < 0.001) between the groups. The n10 latency was prolonged in both groups of patients compared to the control group and there was no statistically significant difference between groups of patients. Furthermore, the amplitude of n10-p15 was lower in both groups of patients compared to the control group and there were no statistically demonstrable differences between the groups of patients. Conclusions: In conclusion, our results suggest that SARS-CoV-2 may affect the vestibulocochlear system. But we could not find a direct relationship according to the severity of the disease.

Picornavirus May Be Linked to Parkinson's Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra.

Parkinson’s disease (PD) is a neurodegenerative disease linked with the loss of dopaminergic neurons in the brain region called substantia nigra and caused by unknown pathogenic mechanisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogenesis of the disease. We investigated formalin-fixed post-mortem brain tissue from 9 patients with Parkinson’s disease and 11 controls for the presence of Ljungan virus (LV) antigen using a polyclonal antibody against the capsid protein of this recently identified picornavirus with neurotropic properties, suspected of being both a human and an animal pathogen. Evidence of viral antigen was found in 7 out of 9 Parkinson’s disease cases and in only 1 out of 11 controls (p = 0.005). The picornavirus antigen was present in dopamine-containing neurons of the substantia nigra. We propose that LV or an LV-related virus initiates the pathological process underlying sporadic PD. LV-related picornavirus antigen has also been reported in patients with Alzheimer’s disease. Potentially successful antiviral treatment in Alzheimer’s disease suggests a similar treatment for Parkinson's disease. Amantadine, originally developed as an antiviral drug against influenza infection, has also been used for symptomatic treatment of patients with PD for more than 50 years and is still commonly used by neurologists today. The fact that amantadine also has an antiviral effect on picornaviruses opens the question of this drug being re-evaluated as potential PD therapy in combination with other antiviral compounds directed against picornaviruses.