Repurposing a digital kitchen scale for neuroscience research: a complete hardware and software cookbook for PASTA.

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.

Nine-month follow-up of the insulin receptor signalling cascade in the brain of streptozotocin rat model of sporadic Alzheimer's disease.

Sporadic Alzheimer disease (sAD) is associated with impairment of insulin receptor (IR) signalling in the brain. Rats used to model sAD develop insulin-resistant brain state following intracerebroventricular treatment with a betacytotoxic drug streptozotocin (STZ-icv). Brain IR signalling has been explored usually at only one time point in periods ≤3 months after the STZ-icv administration. We have investigated insulin signalling in the rat hippocampus at five time points in periods ≤9 months after STZ-icv treatment. Male Wistar rats were given vehicle (control)- or STZ (3 mg/kg)-icv injection and killed 0.5, 1, 3, 6 and 9 months afterwards. Insulin-1 (Ins-1), IR, phospho- and total (p/t)-glycogen synthase kinase 3-ß (GSK-3ß), p/t-tau and insulin degrading enzyme (IDE) mRNA and/or protein were measured. Acute upregulation of tau and IR mRNA (p < 0.05) was followed by a pronounced downregulation of Ins-1, IR and IDE mRNA (p < 0.05) in the course of time. Acute decrement in p/t-tau and p/t-GSK-3ß ratios (p < 0.05) was followed by increment in both ratios (3-6 months, p < 0.05) after which p/t-tau ratio demonstrated a steep rise and p/t-GSK-3ß ratio a steep fall up to 9 months (p < 0.05). Acute decline in IDE and IR expression (p < 0.05) was followed by a slow progression of the former and a slow recovery of the latter in 3-9 months. Results indicate a biphasic pattern in time dependency of onset and progression of changes in brain insulin signalling of STZ-icv model (partly reversible acute toxicity and chronic AD-like changes) which should be considered when using this model as a tool in translational sAD research.

Brain catalase in the streptozotocin-rat model of sporadic Alzheimer's disease treated with the iron chelator-monoamine oxidase inhibitor, M30.

Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.

Antioxidant capacity in rat brain after intracerebroventricular treatment with streptozotocin and alloxan--a preliminary study.

Intracerebroventricular (icv) administration of betacytotoxic drug streptozotocin (STZ) produces long-term and progressive cognitive deficits in rats, as well as deficits in cerebral glucose and energy metabolism. These changes resemble those found in the brain of patients with sporadic Alzheimer's disease (sAD), and therefore, STZ-icv treated rats have been proposed as an experimental model of sAD. In this study the antioxidant capacity (AC), using manual oxygen radical absorbance capacity (ORAC) assay, was measured in the rat brain frontoparietal cortex (FC) and brainstem-cerebellum region (BS-CB) after administration of STZ and another betacytotoxic drug alloxan (AL). Region-specific differences of AC were found, which were more expressed when hydroxyl radical (ORAC(-OHo)) generator was used in the assay. AC against ORAC(-OHo) was significantly lower in BS-CB than in FC of the control rats. Furthermore, ORAC(-OHo) significantly decreased in BS-CB 3-months following the icv administration of AL, but significantly increased following the TG+AL combined treatment in comparison with the controls. However, 3-months following the icv treatment of AL combination with a different glucose transport inhbitor, 3-O-methyl-D-glucose, ORAC(-OHo) values in BS-CB and ORAC(-ROOo) values in FC were significantly decreased in comparison to the controls. Our results suggest that betacytotoxic-icv treatment alters antioxidant defense systems in the brain, which particularly regarding the STZ-icv treatment, could be a useful tool in search for possible new antioxidant treatments of the neurodegenerative disorders such as sAD.

Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach.

A growing body of evidence implicates impairments in brain insulin signaling in early sporadic Alzheimer disease (sAD) pathology. However, the most widely accepted hypothesis for AD aetiology stipulates that pathological aggregations of the amyloid beta (Abeta) peptide are the cause of all forms of Alzheimer's disease. Streptozotocin-intracerebroventricularly (STZ-icv) treated rats are proposed as a probable experimental model of sAD. The current work reviews evidence obtained from this model indicating that central STZ administration induces brain pathology and behavioural alterations resembling those in sAD patients. Recently, alterations of the brain insulin system resembling those in sAD have been found in the STZ-icv rat model and are associated with tau protein hyperphosphorylation and Abeta-like aggregations in meningeal vessels. In line with these findings the hypothesis has been proposed that insulin resistance in the brain might be the primary event which precedes the Abeta pathology in sAD.

Brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer's disease and diabetes mellitus.

It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer's disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly (STZ-icv) treated rats, in which antioxidant capacity against peroxyl (ORAC(-ROO)*) and hydroxyl (ORAC(-OH)*) free radical was measured in three different brain regions (hippocampus, cerebellum, and brain stem) by means of oxygen radical absorbance capacity (ORAC) assay. In the brain of both STZ-induced diabetic and STZ-icv treated rats decreased antioxidant capacity has been found demonstrating regionally specific distribution. In the diabetic rats these abnormalities were not associated with the development of peripheral diabetic neuropathy. Also, these abnormalities were not prevented by the icv pretreatment of glucose transport inhibitor 5-thio-D-glucose in the STZ-icv treated rats, suggesting different mechanism for STZ-induced central effects from those at the periphery. Similarities in the oxidative stress alterations in the brain of STZ-icv rats and humans with sAD could be useful in the search for new drugs in the treatment of sAD that have antioxidant activity.

Central administration of alloxan impairs glucose tolerance in rats.

By means of oral glucose tolerance test (OGTT), we investigated glucose tolerance in rats pre-treated with intracerebroventricular and subcutaneous non-diabetogenic dose of betacytotoxic drug alloxan 7 days before OGTT. Being normoglycemic and normoinsulinemic pre-OGTT, at 30 minutes post-OGTT, alloxan intracerebroventricularly-treated rats had a lower glucose and a higher insulin plasma levels in comparison with controls or alloxan subcutaneously treated animals. Centrally administered alloxan seems to have brain related effect on the regulation of peripheral glucose tolerance and insulin secretion.

Intracerebroventricular administration of betacytotoxics alters expression of brain monoamine transporter genes.

Intracerebroventricular (icv) administration of betacytotoxics alters brain monoamine neurotransmission, without producing hyperglycemia. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline and serotonin transporter (DAT, NAT, 5-HTT, respectively) mRNAs, in the brain of alloxan- and streptozotcin-icv treated rats. DAT1 mRNA expression is increased in 1-week alloxan-icv treated rats in arcuate nucleus (+51%) and ventral medial bundle /VMB/ (+32%), and decrease in VMB of 4-week alloxan- (-53%) and streptozotocin- (-9%) icv treated rats, respectively. NAT1 mRNA expression in locus coeruleus is decreased in 4-week alloxan-icv treated rats (-35%) and increased in A1 cell group of 1- (+19%) and 4- (+14%) week streptozotocin-icv treated rats. 5-HTT mRNA expression in dorsal raphe nucleus is increased in 1- (+13%) and 4- (+21%) week alloxan-icv treated rats. Observed changes may suggest altered response to antidepressants in streptozotocin-icv treated rats, used as an animal model of sporadic Alzheimer's disease.

Usage of the Internet pharmacology resources among European pharmacologists: a preliminary investigation.

The Internet is becoming an ever more important source of information in pharmacology and medicine. Little is known, however, about which Internet pharmacology resources are actually used by the pharmacologists - and to what extent - and how they estimate the Internet information quality and evaluation. This pilot study used an anonymous questionnaire, distributed among 250 mostly European (220/250) pharmacologists from 30 European countries attending The 2nd European Congress of Pharmacology, held in Budapest, Hungary, in 1999. According to study results, 93% of all participants use the Internet pharmacology resources: 56%, 35% and 9% of them on a daily, weekly and monthly basis, respectively. Among 56 pharmacological/medical free online databases offered, the general scientific databases were found to greatly prevail (Pub Med 60%, Evaluated MEDLINE 37%, Internet Grateful Med 29%, etc.), while drug monographs or toxicological databases were less used [e.g. ECDIN, RxList, National Toxicology Programme (NTP) < 10%]. Some 80% of the participants estimated the quality of the pharmacological information on the Internet as good or very good, while 20% thought the quality should be improved. Also, 35% of participants felt the need for improvement of the Internet pharmacological information evaluation, which should be the goal of pharmacology professional.

[Chemical warfare agents]. / Bojni otrovi.

In this article a chemical weapons are reviewed. Most important groups and some of the agents are presented as well as the mechanism of their action, symptoms and therapy.