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Alexander H Tuttle, Mark J Molinaro, Jasmine F Jethwa, Susana G Sotocinal, Juan C Prieto, Martin A Styner, Jeffrey S Mogil, Mark J Zylka
Grimace scales quantify characteristic facial expressions associated with spontaneous pain in rodents and other mammals. However, these scales have not been widely adopted largely because of the time and effort required for highly trained humans to manually score the images. Convoluted neural networks were recently developed that distinguish individual humans and objects in images. Here, we trained one of these networks, the InceptionV3 convolutional neural net, with a large set of human-scored mouse images...
January 2018: Molecular Pain
Andrea J Santamaría, Juan P Solano, Francisco D Benavides, James D Guest
Cell transplant-mediated tissue repair of the damaged spinal cord is being tested in several clinical trials. The current candidates are neural stem cells, stromal cells, and autologous Schwann cells (aSC). Due to their peripheral origin and limited penetration of astrocytic regions, aSC are transplanted intralesionally as compared to neural stem cells that are transplanted into intact spinal cord. Injections into either location can cause iatrogenic injury, and thus technical precision is important in the therapeutic risk-benefit equation...
2018: Methods in Molecular Biology
Adriana E Brooks, Gagani Athauda, Mary Bartlett Bunge, Aisha Khan
Cell-based therapies have become a major focus in preclinical research that leads to clinical application of a therapeutic product. Since 1990, scientists at the Miami Project to Cure Paralysis have generated extensive data demonstrating that Schwann cell (SC) transplantation supports spinal cord repair in animals with spinal cord injury. After preclinical efforts in SC transplantation strategies, efficient methods for procuring large, essentially pure populations of SCs from the adult peripheral nerve were developed for rodent and pig studies...
2018: Methods in Molecular Biology
Kristine M Ravelo, Natalia D Andersen, Paula V Monje
To date, magnetic-activated cell sorting (MACS) remains a powerful method to isolate distinct cell populations based on differential cell surface labeling. Optimized direct and indirect MACS protocols for cell immunolabeling are presented here as methods to divest Schwann cell (SC) cultures of contaminating cells (specifically, fibroblast cells) and isolate SC populations at different stages of differentiation. This chapter describes (1) the preparation of single-cell suspensions from established human and rat SC cultures, (2) the design and application of cell selection strategies using SC-specific (p75NGFR , O4, and O1) and fibroblast-specific (Thy-1) markers, and (3) the characterization of both the pre- and post-sorting cell populations...
2018: Methods in Molecular Biology
Natalia D Andersen, Paula V Monje
Adult Schwann cell (SC) cultures are usually derived from nerves subjected to a lengthy step of pre-degeneration to facilitate enzymatic digestion and recovery of viable cells. To overcome the need for pre-degeneration, we developed a method that allows the isolation of adult rat sciatic nerve SCs immediately after tissue harvesting. This method combines the advantages of implementing a rapid enzymatic dissociation of the nerve fibers and a straightforward separation of cells versus myelin that improves both cell yield and viability...
2018: Methods in Molecular Biology
Rhona Mirsky, Kristjan R Jessen
Schwann cell precursors are the first defined stage in the generation of Schwann cells from the neural crest and represent the glial cell of embryonic nerves. Highly pure cultures of these cells can be obtained by enzymatic dissociation of nerves dissected from the limbs of 14- or 12-day-old rat and mouse embryos, respectively. Since Schwann cell precursors, unlike Schwann cells, are acutely dependent on axonal signals for survival, they require addition of trophic factors, typically β-neuregulin-1, for maintenance in cell culture...
2018: Methods in Molecular Biology
Cyndya A Shibao, Jorge E Celedonio, Robyn Tamboli, Reem Sidani, Latisha Love-Gregory, Terri Pietka, Yanhua Xiong, Yan Wei, Naji N Abumrad, Nada A Abumrad, Charles Robb Flynn
Context: Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism but whether it has similar actions in humans is unknown. We examined impact of a coding single-nucleotide polymorphism in CD36 on post-prandial hormone and bile acid (BA) responses. Objective: To examine if the minor allele (G) of coding CD36 variant rs3211938 (G/T) which reduces CD36 level by approximately 50% influences hormonal responses to a high-fat meal (HFM)...
March 12, 2018: Journal of Clinical Endocrinology and Metabolism
Jung-Heun Ha, Caglar Doguer, Shireen R L Flores, Tao Wang, James F Collins
Background: Consumption of a high-iron diet causes copper deficiency in weanling rodents; however, the minimum amount of dietary iron that disrupts copper homeostasis has not been established. Objective: We tested the hypothesis that dietary iron at only several-fold above physiologic requirements would cause copper depletion. Methods: Weanling male Sprague-Dawley rats (n = 6/group) were fed AIN-93G-based diets with adequate (88 µg Fe/g = 1×), or excessive (4×, 9...
March 1, 2018: Journal of Nutrition
Dorothy W Gietzen, Sarah H Lindström, James W Sharp, Pok Swee Teh, Michael J Donovan
Background: Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. Objective: We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. Methods: In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for ≥7 d, and tested for seizures using various stimuli...
March 1, 2018: Journal of Nutrition
Jianming Luo, Yuetong Li, Jinli Xie, Lijuan Gao, Liu Liu, Shiyi Ou, Long Chen, Xichun Peng
Bacterial interactions in the biological network affect the growth of Bifidobacterium. In the present study, five habitats were constructed by changing animals, their health statuses and their diets. In each of these habitats, different networks of Bifidobacterium were outlined through correlation analysis of the 50 most dominant microbes. Thirty-eight bacterial genera directly correlated with the growth of Bifidobacterium, including 23 genera with a positive correlation and 15 genera with a negative correlation...
March 13, 2018: FEMS Microbiology Letters
Meng-Lin Liu, Meng-Long Wang, Jing-Jun Lv, Jie Wei, Jun Wan
Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, little is known about the role of Gli in ADR-induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR-induced cardiotoxicity in rats...
April 2018: Experimental and Therapeutic Medicine
Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
Luba Sominsky, Christine L Jasoni, Hannah Twigg, Sarah J Spencer
The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adult function established postnatally, and maintained throughout adult life. The perinatal period is highly susceptible to environmental insults that, by disrupting critical developmental processes, can set the tone for the establishment of adult functionality...
March 15, 2018: Journal of Endocrinology
Daniel E O'Brien, Douglas M Shaw, Hyekyung P Cho, Alan J Cross, Steven S Wesolowski, Andrew S Felts, Jonas Bergare, Charles S Elmore, Craig W Lindsley, Colleen M Niswender, P Jeffrey Conn
Allosteric modulation of metabotropic glutamate receptor 2 (mGlu2) has demonstrated efficacy in preclinical rodent models of several brain disorders, leading to industry and academic drug discovery efforts. Although the pharmacology and binding sites of some mGlu2 allosteric modulators have been characterized previously, questions remain about the nature of the allosteric mechanism of cooperativity with glutamate and whether structurally diverse allosteric modulators bind in an identical manner to specific allosteric sites...
March 15, 2018: Molecular Pharmacology
Laura B Tucker, Alexander G Velosky, Joseph T McCabe
Acquired traumatic brain injury (TBI) is frequently accompanied by persistent cognitive symptoms, including executive function disruptions and memory deficits. The Morris Water Maze (MWM) is the most widely-employed laboratory behavioral test for assessing cognitive deficits in rodents after experimental TBI. Numerous protocols exist for performing the test, which has shown great robustness in detecting learning and memory deficits in rodents after infliction of TBI. We review applications of the MWM for the study of cognitive deficits following TBI in pre-clinical studies, describing multiple ways in which the test can be employed to examine specific aspects of learning and memory...
March 12, 2018: Neuroscience and Biobehavioral Reviews
Carolyn M Bauer, Loreto A Correa, Luis A Ebensperger, L Michael Romero
The Common Degu (Octodon degus) is a small rodent endemic to central Chile. It has become an important model for comparative vertebrate endocrinology because of several uncommon life-history features - it is diurnal, shows a high degree of sociality, practices plural breeding with multiple females sharing natal burrows, practices communal parental care, and can easily be studied in the laboratory and the field. Many studies have exploited these features to make contributions to comparative endocrinology. This review summarizes contributions in four major areas...
March 12, 2018: General and Comparative Endocrinology
Charles V Vorhees, Jenna N Sprowles, Samantha L Regan, Michael T Williams
High throughput screens for developmental neurotoxicity (DN) will facilitate evaluation of chemicals and can be used to prioritize those designated for follow-up. DN is evaluated under different guidelines. Those for drugs generally include peri- and postnatal studies and juvenile toxicity studies. For pesticides and commercial chemicals, when triggered, include developmental neurotoxicity studies (DNT) and extended one-generation reproductive toxicity studies. Raffaele et al. (2010) reviewed 69 pesticide DNT studies and found two of the four behavioral tests underperformed...
March 12, 2018: Toxicology and Applied Pharmacology
Peyton W Weems, Michael N Lehman, Lique M Coolen, Robert L Goodman
Work over the last 15 years on the control of pulsatile LH secretion has focused largely on a set of neurons in the arcuate nucleus (ARC) that contains two stimulatory neuropeptides, critical for fertility in humans (kisspeptin and neurokinin B (NKB)) and the inhibitory endogenous opioid peptide (EOP), dynorphin, and are now known as KNDy (kisspeptin-NKB-dynorphin) neurons. In this review, we consider the role of each of the KNDy peptides in the generation of GnRH pulses and the negative feedback actions of ovarian steroids, with an emphasis on NKB and dynorphin...
2018: Vitamins and Hormones
Santosh R Alluri, Patrick J Riss
We report the synthesis, radiosynthesis, and characterization of a radioligand for poly(ADP-ribose) polymerase (PARP). PARP is of central importance in cell homeostasis, neuroplasticity, and neurodegeneration in the brain. A radiolabeled PARP inhibitor was developed and used for autoradiographic quantification of PARP protein concentration in wild-type and transgenic rodent brains ex vivo in high resolution. The binding of [3 H]rucaparib was found to be confined to PARP-expressing domains, for example, cerebellar cortex or hippocampal regions in both models...
March 16, 2018: ACS Chemical Neuroscience
Ken W S Ashwell, Boaz Shulruf
We have used an unbiased statistical approach to compare the pace of development in the main and accessory olfactory systems in monotremes and metatherians with that in rodents and humans. We hypothesized that if metatherians and monotremes, which are born at small body size, use olfaction to locate the pouch and/or teat/milk field, then olfactory structures should reach structural maturity in metatherians and monotremes at a smaller size than eutherians like humans and rodents. The achievement of key structural milestones in the development of the main and accessory olfactory systems (11 and 7 milestones, respectively) was scored for 354 specimens and compared against a measure of general somatic growth (body length)...
March 15, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
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