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.

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.

Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive parameters in a rat model of sAD. Adult male Wistar rats were randomized to a control (CTR), an sAD-model group induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg), a CTR+SGLTI, or an STZ-icv+SGLTI group. Two-month-long oral (gavage) SGLTI treatment (10 mg/kg) was initiated 1 month after STZ-icv and cognitive performance tested prior to sacrifice. SGLTI treatment significantly decreased plasma glucose levels only in the CTR group and failed to correct STZ-icv-induced cognitive deficit. In both the CTR and STZ-icv groups, SGLTI treatment diminished weight gain, decreased amyloid beta (Aβ) 1-42 in duodenum, and decreased the plasma levels of total glucagon-like peptide 1 (GLP-1), while the levels of active GLP-1, as well as both total and active glucose-dependent insulinotropic polypeptide, remained unchanged, compared to their respective controls. The increment in GLP-1 levels in the cerebrospinal fluid and its effect on Aβ 1-42 in duodenum could be one of the molecular mechanisms by which SGLTIs indirectly induce pleiotropic beneficial effects.

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.