Observed metabolic changes in male Wistar rats after treatment with an antidepressant implied in undesirable weight gain, or Sutherlandia frutescens for Type II diabetes

Type II diabetes is fast becoming a growing problem in developed countries worldwide. Traditionally the median age for diagnosis was around sixty, but recent surveys have shown that the entire age distribution curve has shifted to the left. Western countries boast the worst statistics in which type II diabetes is being reported in children under the age of ten. At such a young age the disease often goes undiagnosed for long periods of time allowing considerable damage to occur. The incidence of type II diabetes is thought to be parallel with the growing rate of obesity associated with a characteristically unhealthy western diet. Type II diabetes is an extremely expensive disease to manage, and with the rapid growth of this pandemic our country will soon feel the economic burden of this disease. It is for this reason that cheaper medication needs to be investigated in the form of traditional plants, such as Sutherlandia frutescens. Prescription medication, such as tricyclic antidepressants, may also increase body weight or appetite thereby playing a role in obesity. The cause of weight gain in such cases may go unrecognized or lead to cessation of the medication with or without the practitioner’s knowledge or approval. It is therefore necessary to investigate the causative agents responsible for the excessive weight gain. Drinking water containing extracts of the S. frutescens, metformin (a well known type II diabetes medication) and amitriptyline (a common tricyclic antidepressant) was administered to three groups of ten male Wistar rats. The control group received water without any medication. The rat’s weight and food consumption was monitored throughout the trial and their oxygen consumption was also determined. Rats were sacrificed after four months of medicinal compliance and glucose uptake, in the presence and absence of insulin, was tested in epididymal fat, liver and muscle. Fasting plasma glucose levels, lipoprotein, cholesterol and triglyceride concentrations were also determined

Metabolic effects brought about by tricyclic antidepressants and the contribution of a medicinal plant in alleviating high fat diet induced insulin resistance in male wistar rats

Type II diabetes is becoming a growing problem in developed countries worldwide. The median age for diagnosis was around sixty, but recent surveys have shown that the entire age distribution curve shifting left. The incidence of type II diabetes is thought to be parallel with the growing rate of obesity associated with an unhealthy western diet. Type II diabetes is an expensive disease to manage, it is for this reason that cheaper medication needs to be investigated in the form of traditional plants, such as Sutherlandia frutescens. Prescription medication, such as tricyclic antidepressants, may also increase body weight thereby playing a role in obesity. The cause of weight gain in such cases may go unrecognized or lead to cessation of the medication with or without the practitioner’s knowledge or approval. It is therefore necessary to investigate the causative agents responsible for the excessive weight gain. Drinking water containing extracts of S. frutescens or metformin was administered to two groups of eleven insulin resistant male Wistar rats. The insulin resistant control group received water without any medication. Rats were sacrificed after 8 weeks allowing for fasting blood glucose, insulin and tissue glycogen content determination. Glucose uptake was also determined using [3H] deoxyglucose. The effect of the medication and the diet on muscle post receptor insulin signaling proteins was determined through Western blots. Liver proteomics was also performed using 2-D electrophoresis. In a separate experiment 26 male Wistar rats were exposed to strepotozotocin toxin, 7 of these rats received intravenous insulin treatment, 7 rats received S. frutescens extract and 7 rats received a combination of both medications, the remaining 5 received no treatment and served as the control. Rats were sacrificed after 6 days allowing for fasting blood glucose, insulin and tissue glycogen content determination. Two groups of 14 male Wistar rats received amitriptyline or trimipramine (common tricyclic antidepressants) in their drinking water, the control group (30 rats) received water without any medication. The rats’ weight and food consumption was monitored throughout the trial and their oxygen consumption was also determined. Rats were sacrificed after 6 weeks or 14 weeks of medicinal compliance allowing for fasting blood glucose, insulin and tissue glycogen content determination. Glucose uptake was also determined using [3H] deoxyglucose. S. frutescens treatment normalized circulating serum insulin levels and significantly increased the rate of glucose clearance. Certain post receptor insulin signaling proteins were also significantly increased relative to the insulin resistant control group. 2-D electrophoresis identified the normalization of protein levels associated with the urea cycle. S. frutescens was also able to, independently; maintain normoglycaemic levels in the strepotozotocin treated group. The tricyclic antidepressants significantly increased blood glucose levels while significantly reducing tissue glycogen levels for both sacrifice periods. Serum insulin remained unchanged while a significant increase in insulin degradation and insulin degrading enzyme levels were found for both antidepressants. S. frutescens shows promise as a low cost antidiabetic medication for future use. Although the antidepressants did not promote weight gain, the increase in blood glucose levels may be cause for concern in patients with a pre-disposition toward developing diabetes

Initial Investigations of the cranial size and shape of adult Eurasian otters (Lutra lutra) in Great Britain

Three-dimensional (3D) surface scans were carried out in order to determine the shapes of the upper sections of (skeletal) crania of adult Eurasian otters (Lutra lutra) from Great Britain. Landmark points were placed on these shapes using a graphical user interface (GUI) and distance measurements (i.e., the length, height, and width of the crania) were found by using the landmark points. Male otters had significantly larger skulls than females (P < 0.001). Differences in size also occurred by geographical area in Great Britain (P < 0.05). Multilevel Principal Components Analysis (mPCA) indicated that sex and geographical area explained 31.1% and 9.6% of shape variation in “unscaled” shape data and that they explained 17.2% and 9.7% of variation in “scaled” data. The first mode of variation at level 1 (sex) correctly reflected size changes between males and females for “unscaled” shape data. Modes at level 2 (geographical area) also showed possible changes in size and shape. Clustering by sex and geographical area was observed in standardized component scores. Such clustering in a cranial shape by geographical area might reflect genetic differences in otter populations in Great Britain, although other potentially confounding factors (e.g., population age-structure, diet, etc.) might also drive regional differences. This work provides a successful first test of the effectiveness of 3D surface scans and multivariate methods, such as mPCA, to study the cranial morphology of otters

Repetitive Peroxide Exposure Reveals Pleiotropic Mitogen-Activated Protein Kinase Signaling Mechanisms

Oxidative stressors such as hydrogen peroxide control the activation of many interconnected signaling systems and are implicated in neurodegenerative disease etiology. Application of hydrogen peroxide to PC12 cells activated multiple tyrosine kinases (c-Src, epidermal growth factor receptor (EGFR), and Pyk2) and the serine-threonine kinase ERK1/2. Peroxide-induced ERK1/2 activation was sensitive to intracellular calcium chelation and EGFR and c-Src kinase inhibition. Acute application and removal of peroxide allowed ERK1/2 activity levels to rapidly subside to basal serum-deprived levels. Using this protocol, we demonstrated that ERK1/2 activation tachyphylaxis developed upon repeated peroxide exposures. This tachyphylaxis was independent of c-Src/Pyk2 tyrosine phosphorylation but was associated with a progressive reduction of peroxide-induced EGFR tyrosine phosphorylation, EGFR interaction with growth factor receptor binding protein 2, and a redistribution of EGFR from the plasma membrane to the cytoplasm. Our data indicates that components of peroxide-induced ERK1/2 cascades are differentially affected by repeated exposures, indicating that oxidative signaling may be contextually variable

Cortical gene transcription response patterns to water maze training in aged mice

<p>Abstract</p> <p>Background</p> <p>The hippocampus mediates the acquisition of spatial memory, but the memory trace is eventually transferred to the cortex. We have investigated transcriptional activation of pathways related to cognitive function in the cortex of the aged mouse by analyzing gene expression following water maze training.</p> <p>Results</p> <p>We identified genes that were differentially responsive in aged mice with accurate spatial performance during probe trials or repeated swimming sessions, relative to home cage conditions. Effective learners exhibited significantly greater activation of several pathways, such as the mitogen-activated protein kinase and insulin receptor signaling pathways, relative to swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners, relative to swimmers and home cage controls, while the gene encoding Rho GTPase activating protein 32 (GRIT) was downregulated. We explored the regulation of Arc, BDNF, and GRIT expression in greater morphological detail using in situ hybridization. Recall during probe trials enhanced Arc expression across multiple cortical regions involved in the cognitive component of water maze learning, while BDNF expression was more homogeneously upregulated across cortical regions involved in the associational and sensorimotor aspects of water maze training. In contrast, levels of GRIT expression were uniformly reduced across all cortical regions examined.</p> <p>Conclusions</p> <p>These results suggest that cortical gene transcription is responsive to learning in aged mice that exhibit behavioral proficiency, and support a distributed hypothesis of memory storage across multiple cortical compartments.</p

Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted Adaptive Responses

Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations

VENNTURE–A Novel Venn Diagram Investigational Tool for Multiple Pharmacological Dataset Analysis

As pharmacological data sets become increasingly large and complex, new visual analysis and filtering programs are needed to aid their appreciation. One of the most commonly used methods for visualizing biological data is the Venn diagram. Currently used Venn analysis software often presents multiple problems to biological scientists, in that only a limited number of simultaneous data sets can be analyzed. An improved appreciation of the connectivity between multiple, highly-complex datasets is crucial for the next generation of data analysis of genomic and proteomic data streams. We describe the development of VENNTURE, a program that facilitates visualization of up to six datasets in a user-friendly manner. This program includes versatile output features, where grouped data points can be easily exported into a spreadsheet. To demonstrate its unique experimental utility we applied VENNTURE to a highly complex parallel paradigm, i.e. comparison of multiple G protein-coupled receptor drug dose phosphoproteomic data, in multiple cellular physiological contexts. VENNTURE was able to reliably and simply dissect six complex data sets into easily identifiable groups for straightforward analysis and data output. Applied to complex pharmacological datasets, VENNTURE’s improved features and ease of analysis are much improved over currently available Venn diagram programs. VENNTURE enabled the delineation of highly complex patterns of dose-dependent G protein-coupled receptor activity and its dependence on physiological cellular contexts. This study highlights the potential for such a program in fields such as pharmacology, genomics, and bioinformatics

Airborne radar imaging of subaqueous channel evolution in Wax Lake Delta, Louisiana, USA

Shallow coastal regions are among the fastest evolving landscapes but are notoriously difficult to measure with high spatiotemporal resolution. Using Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) data, we demonstrate that high signal‐to‐noise L band synthetic aperture radar (SAR) can reveal subaqueous channel networks at the distal ends of river deltas. Using 27 UAVSAR images collected between 2009 and 2015 from the Wax Lake Delta in coastal Louisiana, USA, we show that under normal tidal conditions, planform geometry of the distributary channel network is frequently resolved in the UAVSAR images, including ~700 m of seaward network extension over 5 years for one channel. UAVSAR also reveals regions of subaerial and subaqueous vegetation, streaklines of biogenic surfactants, and what appear to be small distributary channels aliased by the survey grid, all illustrating the value of fine resolution, low noise, L band SAR for mapping the nearshore subaqueous delta channel network

Multiple Oxygen Tension Environments Reveal Diverse Patterns of Transcriptional Regulation in Primary Astrocytes

The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity