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Accumulating evidence supports the involvement of the gastrointestinal (GI) system in Alzheimer’s disease (AD), however, it is currently unknown whether GI alterations arise as a consequence of central nervous system (CNS) pathology or play a causal role in the pathogenesis of the disease. The GI mucus system is a possible mediator of GI dyshomeostasis in neurological disorders as CNS controls mucus production and secretion via the efferent arm of the brain-gut axis. The aim was to use a brain-first model of sporadic AD induced by intracerebroventricular streptozotocin (STZ-icv) to dissect the efferent (i.e. brain-to-gut) effects of isolated central neuropathology on the GI mucus system. Quantification and morphometric analysis of goblet cell mucigen granules revealed altered GI mucus secretion in the AD model possibly mediated by the insensitivity of AD goblet cells to neurally-evoked mucosal secretion confirmed by ex vivo cholinergic stimulation of isolated duodenal rings. The dysfunctional efferent control of the GI mucus secretion results in altered biochemical composition of the mucus associated with reduced glycoprotein aggregation and binding capacity in vitro. Finally, functional consequences of the reduced barrier-forming capacity of the AD mucus are demonstrated using the in vitro two-compartment caffeine diffusion interference model. Isolated central AD-like neuropathology results in the loss of efferent control of GI homeostasis via the brain-gut axis characterized by the insensitivity to neurally-evoked mucosal secretion, altered mucus constitution, and reduced barrier-forming capacity potentially increasing the susceptibility of STZ-icv rat model of AD to GI and systemic inflammation induced by intraluminal toxins, microorganisms, and drugs.

The gut-brain axis plays an important role in Parkinson’s disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Univariate and multivariate models of redox biomarkers provide solid evidence against the existence of pronounced gastrointestinal redox dyshomeostasis. The results indicate that the dysfunction of the nigro-vagal system and not motor deficit may be a key mediator of gastrointestinal dyshomeostasis in brain-first 6-OHDA-induced rodent models of PD.

Introduction: The Pandemic of COVID-19, an infectious disease caused by SARS-CoV-2 motivated the scientific community to work together in order to gather, organize, process and distribute data on the novel biomedical hazard. Here, we analyzed how the scientific community responded to this challenge by quantifying distribution and availability patterns of the academic information related to COVID-19. The aim of our study was to assess the quality of the information flow and scientific collaboration, two factors we believe to be critical for finding new solutions for the ongoing pandemic. Materials and Methods: The RISmed R package, and a custom Python script were used to fetch metadata on articles indexed in PubMed and published on rXiv preprint server. Scopus was manually searched and the metadata was exported in BibTex file. Publication rate and publication status, affiliation and author count per article, and submission-to-publication time were analysed in R. Biblioshiny application was used to create a world collaboration map. Results: Our preliminary data suggest that COVID-19 pandemic resulted in generation of a large amount of scientific data, and demonstrates potential problems regarding the information velocity, availability, and scientific collaboration in the early stages of the pandemic. More specifically, our results indicate precarious overload of the standard publication systems, delayed adoption of the preprint publishing, significant problems with data availability and apparent deficient collaboration. Conclusion: In conclusion, we believe the scientific community could have used the data more efficiently in order to create proper foundations for finding new solutions for the COVID-19 pandemic. Moreover, we believe we can learn from this on the go and adopt open science principles and a more mindful approach to COVID-19-related data to accelerate the discovery of more efficient solutions. We take this opportunity to invite our colleagues to contribute to this global scientific collaboration by publishing their findings with maximal transparency.

Antioxidant enzyme catalase protects the cells against alcohol-induced oxidative stress by scavenging free radicals and metabolizing alcohol. Concentrations of ethanol present in alcoholic beverages can inhibit catalase and foster oxidative stress and alcohol-induced injury. Non-alcoholic components of pelinkovac counteract the inhibitory effects of high ethanol concentration and acidic pH on catalase in vitro.

Galactose is a ubiquitous monosaccharide with important yet incompletely understood nutritive and physiological roles. Chronic parenteral d-galactose administration is used for modeling aging-related pathophysiological processes in rodents due to its ability to induce oxidative stress (OS). Conversely, chronic oral d-galactose administration prevents and alleviates cognitive decline in a rat model of sporadic Alzheimer’s disease, indicating that galactose may exert beneficial health effects by acting in the gut. The present aim was to explore the acute time-response of intestinal redox homeostasis following oral administration of d-galactose. Male Wistar rats were euthanized at baseline (n = 6), 30 (n = 6), 60 (n = 6), and 120 (n = 6) minutes following orogastric administration of d-galactose (200 mg/kg). The overall reductive capacity, lipid peroxidation, the concentration of low-molecular-weight thiols (LMWT) and protein sulfhydryls (SH), the activity of Mn and Cu/Zn superoxide dismutases (SOD), reduced and oxidized fractions of nicotinamide adenine dinucleotide phosphates (NADPH/NADP), and the hydrogen peroxide dissociation rate were analyzed in duodenum and ileum. Acute oral administration of d-galactose increased the activity of SODs and decreased intestinal lipid peroxidation and nucleophilic substrates (LMWT, SH, NADPH), indicating activation of peroxidative damage defense pathways. The redox system of the small intestine can acutely tolerate even high luminal concentrations of galactose (0.55 M), and oral galactose treatment is associated with a reduction rather than the increment of the intestinal OS. The ability of oral d-galactose to modulate intestinal OS should be further explored in the context of intestinal barrier maintenance, and beneficial cognitive effects associated with long-term administration of low doses of d-galactose.

Scope: Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim is to examine the acute effects of oral galactose on the redox regulatory network (RRN). Methods and Results: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg‒1). No systemic RRN disbalance is observed; however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems is observed in the hippocampus. Galactose-induced increment of reductive capacity is accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. Conclusion: Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects may be inseparable from its pro-oxidative action at the biochemical level.

Galactose is a ubiquitous simple monosaccharide with yet incompletely understood biochemical and physiological role. Most of what we currently know about galactose is based on induction from the research on inherited disorders of galactose metabolism and animal models that exploit galactose-induced oxidative stress to model aging in rodents, however, recent evidence also demonstrates unique properties of galactose to conserve cellular function during the periods of starvation, and prevent and alleviate cognitive deficits in a rat model of sporadic Alzheimer’s disease. Here, we try to understand the molecular background of both detrimental and beneficial effects of galactose by exploring the acute systemic and hippocampal biochemical changes upon oral administration of galactose solution focusing primarily on the components of the redox regulatory network (RRN). Although orogastric gavage of galactose solution (200 mg/kg) was insufficient to induce systemic RRN disbalance in the first two hours upon administration, analysis of hippocampal RRN revealed a mild pro-oxidative shift accompanied by a paradoxical increase in tissue reductive capacity, suggesting overcompensation of endogenous antioxidant systems in the response to the pro-oxidative stimulus. The more thorough analysis revealed that galactose-induced increment of reductive capacity was accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. Based on the observed findings, and in the context of previous work on galactose, we propose a hormetic hypothesis of galactose action suggesting that the protective effects of galactose might be inseparable from its pro-oxidative effects at the biochemical level.

Assessment of neuromuscular function is critical for understanding pathophysiological changes related to motor system dysfunction in many rodent disease models. Among methods used for quantification of grip performance in rodents, gauge-based grip strength meters provide the most reliable results, however, such instruments are unaffordable by many laboratories. Here we demonstrate how to build a rodent grip strength apparatus from scratch using a digital kitchen scale, an empty cage, and a microcontroller, with both hardware and software being completely open-source to enable maximal modularity and flexibility of the instrument in concordance with the principles of open-source bioinstrumentation. Furthermore, we test the griPASTA system for assessment of increased muscular rigidity in the proof-of-concept experiment in the rat model of Parkinson’s disease induced by intrastriatal administration of 6-hydroxydopamine (6-OHDA). Finally, the importance of bioinstrumental customization is demonstrated by utilizing griPASTA for assessment of trial speed from initial-to-maximal deflection time segments and controlling for its potential confounding effects on the grip strength.Significance StatementNeuromuscular function analyzed by grip strength performance tests is an integral part of motor system neuroscience and neurotoxicology. Strain gauge-based grip strength meters provide the most reliable results, however, commercial solutions are unaffordable by many. Consequently, cheap semi-quantitative tests are often used at the expense of precision and reliability. We propose griPASTA – a simple and robust open-source grip strength platform made from an ordinary kitchen scale. griPASTA could improve the quality and reproducibility of grip strength experiments by enabling researchers to obtain quantitative grip strength data in high resolution using a highly customizable platform.

Introduction: A large number of COVID-19 publications has created a need to collect all research-related material in practical and reliable centralized databases. The aim of this study was to evaluate the functionality and quality of the compiled World Health Organisation COVID-19 database and compare it to Pubmed and Scopus. Methods: Article metadata for COVID-19 articles and articles on 8 specific topics related to COVID-19 was exported from the WHO global research database, Scopus and Pubmed. The analysis was conducted in R to investigate the number and overlapping of the articles between the databases and the missingness of values in the metadata. Results: The WHO database contains the largest number of COVID-19 related articles overall but retrieved the same number of articles on 8 specific topics as Scopus and Pubmed. Despite having the smallest number of exclusive articles overall, the highest number of exclusive articles on specific COVID-19 related topics was retrieved from the Scopus database. Further investigation revealed that PubMed and Scopus have more comprehensive structure than the WHO database, and less missing values in the categories searched by the information retrieval systems. Discussion: This study suggests that the WHO COVID-19 database, even though it is compiled from multiple databases, has a very simple and limited structure, and significant problems with data quality. As a consequence, relying on this database as a source of articles for systematic reviews or bibliometric analyses is undesirable.

Highlights • NRP is a rapid, cost-effective and simple method for reductive capacity assessment. • NRP is compatible with high-throughput screening of solid and liquid biological samples. • HistoNRP exploits passive diffusion slice print blotting for reductive capacity spatial analysis., We propose a rapid, simple, and robust method for measurement of the reductive capacity of liquid and solid biological samples based on potassium permanganate reduction followed by trapping of manganese dioxide precipitate on a nitrocellulose membrane. Moreover, we discuss how nitrocellulose redox permanganometry (NRP) can be used for high-throughput analysis of biological samples and present HistoNRP, its modification used for detailed analysis of reductive capacity spatial distribution in tissue with preserved anatomical relations.•NRP is a rapid, cost-effective, and simple method for reductive capacity assessment•NRP is compatible with a high-throughput screening of solid and liquid biological samples•HistoNRP exploits passive diffusion slice print blotting for reductive capacity spatial analysis, Graphical abstract Image, graphical abstract

Widely available low-cost electronics encourage the development of open-source tools for neuroscientific research. In recent years, many neuroscientists recognized the open science movement for its potential to stimulate and encourage science that is less focused on money, and more on robustness, validity, questioning and understanding. Here, we wanted to contribute to this global community by creating a research platform based on a common digital kitchen scale. This everyday ordinary kitchen tool is sometimes used in neuroscience research in various ways; however, its use is limited by sampling rate and inability to store and analyze data. To tackle this problem we developed a Platform for Acoustic STArtle or PASTA. This robust and simple platform enables users to obtain data from kitchen scale load cells at a high sampling rate, store it and analyze it. Here, we used it to analyze acoustic startle and prepulse inhibition sensorimotor gating in rats treated intracerebroventricularly with streptozotocin, but the system can be easily modified and upgraded for other purposes. In accordance with open science principles, we shared complete hardware design with instructions. Furthermore, we also disclose our software codes written for PASTA data acquisition (C++, Arduino) and acoustic startle experimental protocol (Python) and analysis (ratPASTA R package—R-based Awesome Toolbox for PASTA, and pastaWRAP—Python wrapper package for ratPASTA). To further encourage the development of our PASTA platform we demonstrate its sensitivity by using PASTA-gathered data to extract breathing patterns during rat freezing behavior in our experimental protocol.