scholarly journals Macaque monkeys learn and perform a non-match-to-goal task using an automated home cage training procedure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefano Sacchetti ◽  
Francesco Ceccarelli ◽  
Lorenzo Ferrucci ◽  
Danilo Benozzo ◽  
Emiliano Brunamonti ◽  
...  
Keyword(s):  
High Performance ◽  
Home Cage ◽  
Training Procedure ◽  
Macaque Monkeys ◽  
Challenging Tasks ◽  
Electrophysiological Studies ◽  
Stable Performance ◽  
The Brain ◽  
High Performance Level ◽  
Made In

AbstractIn neurophysiology, nonhuman primates represent an important model for studying the brain. Typically, monkeys are moved from their home cage to an experimental room daily, where they sit in a primate chair and interact with electronic devices. Refining this procedure would make the researchers’ work easier and improve the animals’ welfare. To address this issue, we used home-cage training to train two macaque monkeys in a non-match-to-goal task, where each trial required a switch from the choice made in the previous trial to obtain a reward. The monkeys were tested in two versions of the task, one in which they acted as the agent in every trial and one in which some trials were completed by a “ghost agent”. We evaluated their involvement in terms of their performance and their interaction with the apparatus. Both monkeys were able to maintain a constant involvement in the task with good, stable performance within sessions in both versions of the task. Our study confirms the feasibility of home-cage training and demonstrates that even with challenging tasks, monkeys can complete a large number of trials at a high performance level, which is a prerequisite for electrophysiological studies of monkey behavior.

Pharmacokinetics and Tissue Distribution Study of Ferruginol in Wistar Rat by High-performance Liquid Chromatography

2018 ◽  
Vol 15 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Guiyun Cao ◽  
Suqiao Han ◽  
Keke Li ◽  
Li Shen ◽  
Xiaohong Wang ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Mobile Phase ◽  
High Performance ◽  
Wistar Rat ◽  
Freezing And Thawing ◽  
Promising Candidate ◽  
Distribution Study ◽  
Substance Loss ◽  
Tissue Distribution Study ◽  
The Brain

Background: Ferruginol (FRGN) exhibits a broad range of pharmacological properties which make it a promising candidate for chemoprevention. However, little is known about its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: A rapid, sensitive and specific HPLC-DAD method was established to quantify FRGN in the plasma and tissues of Wistar rats. After extraction of FRGN with ethyl acetate (EtOAc), chromatographic separation was performed on a YMC ODS C18 column (250 × 4.6 mm I.D., 5 µm) with a mobile phase consisting of methanol-water (92:8, v/v) at a flow rate of 0.9 mL/min. Detection was conducted with a wavelength of 273 nm at 25 °C. Results: The calibration curves for FRGN were linear in the concentration range of 0.5-20 µg/mL for plasma, 0.5-10 µg/mL for heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle. After three cycles of freezing and thawing, the concentration variations were within ± 7% of nominal concentrations, indicating no significant substance loss during repeated thawing and freezing. The assay was applied to pharmacokinetic and tissue distribution study in rats. Results suggested that lung, heart, liver, spleen and kidney were the major distribution tissues of FRGN in rats, and FRGN could permeate the blood-brain barrier to distribute in the brain of rats. Conclusion: The information provided by this research is very useful for gaining knowledge of the pharmacokinetic process and tissue distribution of FRGN.

scholarly journals A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Changpeng Wang ◽  
Siwei Zhang ◽  
Yuefei Zou ◽  
Hongzhao Ma ◽  
Donglang Jiang ◽  
...  
Keyword(s):  
High Performance ◽  
Specific Activity ◽  
High Accumulation ◽  
Metabolic Kinetics ◽  
Thiamine Metabolism ◽  
Pet Tracer ◽  
The Status ◽  
The Brain

Abstract Background Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed. Methods A novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated. Results The 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015). Conclusion The 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

scholarly journals Brain Levels of Prostaglandins, Endocannabinoids, and Related Lipids Are Affected by Mating Strategies

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Jordyn M. Stuart ◽  
Jason J. Paris ◽  
Cheryl Frye ◽  
Heather B. Bradshaw
Keyword(s):  
Sexual Differentiation ◽  
Home Cage ◽  
Mating Strategies ◽  
Spectrometric Analysis ◽  
Tandem Mass ◽  
Reproductive Behaviors ◽  
Tandem Mass Spectrometric Analysis ◽  
Tandem Mass Spectrometric ◽  
Endogenous Cannabinoids ◽  
The Brain

Background. Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. Likewise, prostaglandins (PGs) drive sexual differentiation and initiation of ovulation. Here, we use lipidomics strategies to test the hypotheses that mating immediately activates the biosynthesis and/or metabolism of eCBs and PGs and that specific mating strategies differentially regulate these lipids in the brain.Methods. Lipid extractions and tandem mass spectrometric analysis were performed on brains from proestrous rats that had experienced one of two mating strategies (paced or standard mating) and two nonmated groups (chamber exposed and home cage controls). Levels of PGs (PGE2 and PGF2alpha), eCBs (AEA and 2-AG,N-arachidonoyl glycine), and 4 related lipids (4N-acylethanolamides) were measured in olfactory bulb, hypothalamus, hippocampus, thalamus, striatum, midbrain, cerebellum, and brainstem.Results. Overall, levels of these lipids were significantly lower among paced compared to standard mated rats with the most dramatic decreases observed in brainstem, hippocampus, midbrain, and striatum. However, chamber exposed rats had significantly higher levels of these lipids compared to home cage controls and paced mated wherein the hippocampus showed the largest increases.Conclusions. These data demonstrate that mating strategies and exposure to mating arenas influence lipid signaling in the brain.

scholarly journals Motivational system modulates brain responses during exploratory decision-making

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chia-Wei Li ◽  
Carol Yeh-Yun Lin ◽  
Ting-Ting Chang ◽  
Nai-Shing Yen ◽  
Danchi Tan
Keyword(s):  
Decision Making ◽  
High Performance ◽  
Behavioral Activation ◽  
Motivational Orientation ◽  
Performance Group ◽  
Reward Seeking ◽  
Brain Responses ◽  
Low Performance ◽  
Risk Choice ◽  
The Brain

AbstractManagers face risk in explorative decision-making and those who are better at such decisions can achieve future viability. To understand what makes a manager effective at explorative decision-making requires an analysis of the manager’s motivational characteristics. The behavioral activation/inhibition system (BAS/BIS), fitting the motivational orientation of “approach” or “avoidance,” can affect individual decision-making. However, very little is known about the neural correlates of BAS/BIS orientation and their interrelationship with the mental activity during explorative decision-making. We conducted an fMRI study on 111 potential managers to investigate how the brain responses of explorative decision-making interact with BAS/BIS. Participants were separated into high- and low-performance groups based on the median exploration-score. The low-performance group showed significantly higher BAS than that of the high-performance group, and its BAS had significant negative association with neural networks related to reward-seeking during explorative decision-making. Moreover, the BIS of the low-performance group was negatively correlated with the activation of cerebral regions responding to risk-choice during explorative decision-making. Our finding showed that BAS/BIS was associated with the brain activation during explorative decision-making only in the low-performance group. This study contributed to the understanding of the micro-foundations of strategically relevant decision-making and has an implication for management development.

Krešimir Krnjević (1927–2021) and GABAergic inhibition: a lifetime dedication

2021 ◽  
pp. 1-4
Author(s):  
Yehezkel Ben-Ari ◽  
Enrico Cherubini ◽  
Massimo Avoli
Keyword(s):  
Canadian Journal ◽  
Chief Editor ◽  
Aminobutyric Acid ◽  
Gabaergic Inhibition ◽  
Inhibitory Neurotransmitter ◽  
Neuroscience Research ◽  
Personal Interactions ◽  
The Brain ◽  
Made In

After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Krešimir Krnjević (1927–2021), a pioneer and leader in neuroscience, we briefly highlight the fundamental contributions he made in identifying GABA as an inhibitory neurotransmitter in the brain and our personal interactions with him. Of note, between 1972 and 1978 Dr. Krnjević was a highly reputed Chief Editor of the Canadian Journal of Physiology and Pharmacology.

Abstract 306: Alamandine but not angiotensin-(1-7) produces cardiovascular effects in the Insular Cortex

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fernanda R Marins ◽  
Aline C Oliveira ◽  
Fatimunnisa Qadri ◽  
Natalia Alenina ◽  
Michael Bader ◽  
...  
Keyword(s):  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Equimolar Dose ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

In the course of experiments aimed to evaluate the immunofluorescence distribution of MrgD receptors we observed the presence of immunoreactivity for the MrgD protein in the Insular Cortex. In order to evaluate the functional significance of this finding, we investigated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Urethane (1.4g/kg) anesthetized rats were instrumented for measurement of MAP, HR and renal sympathetic nerve activity (RSNA). Unilateral microinjection of alamandine (40 pmol/100nl), Angiotensin-(1-7) (40pmol/100nl), Mas/MrgD antagonista D-Pro7-Ang-1-7 (50pmol/100nl), Mas agonist A779 (100 pmol/100nl) or vehicle (0,9% NaCl) were made in different rats (N=4-6 per group) into posterior insular cortex (+1.5mm rostral to the bregma). Microinjection of alamandine in this region produced a long-lasting (> 18 min) increase in MAP (Δ saline= -2±1 vs. alamandine= 12±2 mmHg, p< 0.05) associated to increases in HR (Δ saline= 2±2 vs. alamandine= 35±5 bpm; p< 0.05) and in the amplitude of renal nerve discharges (Δ saline = -2±1 vs. alamandine= 35±5.5 % of the baseline; p< 0.05). Strikingly, an equimolar dose of angiotensin-(1-7) did not produce any change in MAP or HR (Δ MAP=-0.5±0.3 mmHg and +2.7±1.2 bpm, respectively; p> 0.05) and only a slight increase in RSNA (Δ =7.3±3.2 %) . In keeping with this observation the effects of alamandine were not significantly influenced by A-779 (Δ MAP=+13± 2.5 mmHg, Δ HR= +26±3.6 bpm; Δ RSNA = 25± 3.4%) but completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7) (Δ MAP=+0 ± 1 mmHg Δ HR= +4±2.6 bpm; Δ RSNA = 0.5± 2.2 %). Therefore, we have identified a brain region in which alamandine/MrgD receptors but not Ang-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to Ang-(1-7) in the brain.

Febrile Convulsions, by J. Gordon Millichap, M.D., M.R.C.P. New York: The Macmillan Company, 1968, 239 pp., $7.95

PEDIATRICS ◽  
1968 ◽  
Vol 42 (2) ◽  
pp. 381-382
Author(s):  
Randolph K. Byers
Keyword(s):  
New York ◽  
Relevant Literature ◽  
Febrile Seizures ◽  
Cerebral Injury ◽  
Extensive Review ◽  
Cerebral Disease ◽  
Febrile Convulsions ◽  
The Individual ◽  
The Brain ◽  
Made In

This rather modest-looking monograph deals not only with the large experiences of the author in relation to febrile seizures, but also presents an extensive review of the modern relevant literature (266 references in the bibliography). The most useful point made in the book, it seems to me, is that febrile convulsions are just that: i.e., convulsions coinciding with fever, the result of illness not directly involving the brain or its meninges. Such a seizure may be an isolated occurrence in the life of the individual, or it may recur a few times with fever; it may be the first sign of idiopathic chronic epilepsy, or it may be evidence of more or less apparent cerebral injury of a static sort; or, it may be the presenting symptom heralding progressive cerebral disease.

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