The use of rodent models to better characterize the relationship among epilepsy, sleep, and memory

Diet and nutrition are intricately related to cancer prevention, growth, and treatment response. Preclinical rodent models are a cornerstone to biomedical research and remain instrumental in our understanding of the relationship between cancer and diet and in the development of effective therapeutics. However, the success rate of translating promising findings from the bench to the bedside is suboptimal. Well-designed rodent models will be crucial to improving the impact basic science has on clinical treatment options. This review discusses essential experimental factors to consider when designing a preclinical cancer model with an emphasis on incorporating these models into studies interrogating diet, nutrition, and metabolism. The aims of this review are to ( a) provide insight into relevant considerations when designing cancer models for obesity, nutrition, and metabolism research; ( b) identify common pitfalls when selecting a rodent model; and ( c) discuss strengths and limitations of available preclinical models. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Does Diacylglycerol Accumulation in Fatty Liver Disease Cause Hepatic Insulin Resistance?

BioMed Research International ◽

10.1155/2015/104132 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 25

Author(s):

Brian N. Finck ◽

Angela M. Hall

Keyword(s):

Insulin Resistance ◽

Fatty Liver Disease ◽

Large Body ◽

Lipid Mediators ◽

Hepatic Insulin Resistance ◽

Rodent Models ◽

Metabolic Abnormalities ◽

Kinase C ◽

The Relationship ◽

Compare And Contrast

Numerous studies conducted on obese humans and various rodent models of obesity have identified a correlation between hepatic lipid content and the development of insulin resistance in liver and other tissues. Despite a large body of the literature on this topic, the cause and effect relationship between hepatic steatosis and insulin resistance remains controversial. If, as many believe, lipid aggregation in liver drives insulin resistance and other metabolic abnormalities, there are significant unanswered questions as to which lipid mediators are causative in this cascade. Several published papers have now correlated levels of diacylglycerol (DAG), the penultimate intermediate in triglyceride synthesis, with development of insulin resistance and have postulated that this occurs via activation of protein kinase C signaling. Although many studies have confirmed this relationship, many others have reported a disconnect between DAG content and insulin resistance. It has been postulated that differences in methods for DAG measurement, DAG compartmentalization within the cell, or fatty acid composition of the DAG may explain these discrepancies. The purpose of this review is to compare and contrast some of the relevant findings in this area and to discuss a number of unanswered questions regarding the relationship between DAG and insulin resistance.

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The Relationship between Diabetes Mellitus Type II and Intervertebral Disc Degeneration in Diabetic Rodent Models: A Systematic and Comprehensive Review

Cells ◽

10.3390/cells9102208 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2208

Author(s):

Mohamed Mahmoud ◽

Maria Kokozidou ◽

Alexander Auffarth ◽

Gundula Schulze-Tanzil

Keyword(s):

Diabetes Mellitus ◽

Intervertebral Disc ◽

Diabetes Mellitus Type ◽

Diabetic Patients ◽

Rodent Models ◽

Disc Disease ◽

Diabetes Mellitus Type Ii ◽

Glycation End Products ◽

The Relationship

The number of diabetic patients grows constantly worldwide. Many patients suffer simultaneously from diabetes mellitus type 2 (T2DM) and intervertebral disc disease (IVDD), suggesting a strong link between T2DM and IVDD. T2DM rodent models provide versatile tools to study this interrelation. We hypothesized that the previously achieved studies in rodents approved it. Performing a search in the publicly available electronic databases according to our inclusion (e.g., experimental study with clearly outlined methods investigating IVDD in diabetic rodent models) and exclusion (e.g., non-experimental) criteria, we included 23 studies from 1992 to 2020 analyzing different aspects of IVDD in diabetic rodents, such as on pathogenesis (e.g., effects of hyperglycemia on IVD cells, sirtuin (SIRT)1/p53 axis in the interrelation between T2DM and IVDD), risk factors (e.g., high content of advanced glycation end-products (AGEs) in modern diets), therapeutical approaches (e.g., insulin-like growth factor (IGF-I)), and prophylaxis. Regarding their quality, 12 studies were classified as high, six as moderate, and five as low. One strong, 18 moderate, and three mild evidences of the link between DM and IVDD in rodents were found, while only one study has not approved this link. We concluded that T2DM has a devastating effect on IVD, particularly in advanced cases, which needs to be further evaluated.

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Direct relationship between increased expression and mistrafficking of the Charcot–Marie–Tooth–associated protein PMP22

Journal of Biological Chemistry ◽

10.1074/jbc.ac120.014940 ◽

2020 ◽

Vol 295 (34) ◽

pp. 11963-11970 ◽

Cited By ~ 1

Author(s):

Justin T. Marinko ◽

Bruce D. Carter ◽

Charles R. Sanders

Keyword(s):

Dermal Fibroblasts ◽

Rodent Models ◽

Chromosome Fragment ◽

Peripheral Myelin Protein 22 ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Cell Flow Cytometry ◽

Endoplasmic Reticulum Quality Control ◽

The Relationship ◽

Tooth Disease

Charcot–Marie–Tooth disease (CMT) is a neuropathy of the peripheral nervous system that afflicts ∼1:2500 people. The most common form of this disease (CMT1A, 1:4000) is associated with duplication of chromosome fragment 17p11.2-12, which results in a third WT PMP22 allele. In rodent models overexpressing the PMP22 (peripheral myelin protein 22) protein and in dermal fibroblasts from patients with CMT1A, PMP22 aggregates have been observed. This suggests that overexpression of PMP22 under CMT1A conditions overwhelms the endoplasmic reticulum quality control system, leading to formation of cytotoxic aggregates. In this work, we used a single-cell flow-cytometry trafficking assay to quantitatively examine the relationship between PMP22 expression and trafficking efficiency in individual cells. We observed that as expression of WT or disease variants of PMP22 is increased, the amount of intracellular PMP22 increases to a greater extent than the amount of surface-trafficked protein. This was true for both transiently transfected cells and PMP22 stable expressing cells. Our results support the notion that overexpression of PMP22 in CMT1A leads to a disproportionate increase in misfolding and mistrafficking of PMP22, which is likely a contributor to disease pathology and progression.

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pS421 huntingtin modulates mitochondrial phenotypes and confers neuroprotection in an HD hiPSC model

Cell Death and Disease ◽

10.1038/s41419-020-02983-z ◽

2020 ◽

Vol 11 (9) ◽

Author(s):

Xiaohong Xu ◽

Bryan Ng ◽

Bernice Sim ◽

Carola I. Radulescu ◽

Nur Amirah Binte Mohammad Yusof ◽

...

Keyword(s):

Pluripotent Stem Cells ◽

Neurodegenerative Disorder ◽

Protective Role ◽

Neural Cells ◽

Rodent Models ◽

Form And Function ◽

And Function ◽

The Relationship ◽

Genetic Context

Abstract Huntington disease (HD) is a hereditary neurodegenerative disorder caused by mutant huntingtin (mHTT). Phosphorylation at serine-421 (pS421) of mHTT has been shown to be neuroprotective in cellular and rodent models. However, the genetic context of these models differs from that of HD patients. Here we employed human pluripotent stem cells (hiPSCs), which express endogenous full-length mHTT. Using genome editing, we generated isogenic hiPSC lines in which the S421 site in mHTT has been mutated into a phospho-mimetic aspartic acid (S421D) or phospho-resistant alanine (S421A). We observed that S421D, rather than S421A, confers neuroprotection in hiPSC-derived neural cells. Although we observed no effect of S421D on mHTT clearance or axonal transport, two aspects previously reported to be impacted by phosphorylation of mHTT at S421, our analysis revealed modulation of several aspects of mitochondrial form and function. These include mitochondrial surface area, volume, and counts, as well as improved mitochondrial membrane potential and oxidative phosphorylation. Our study validates the protective role of pS421 on mHTT and highlights a facet of the relationship between mHTT and mitochondrial changes in the context of human physiology with potential relevance to the pathogenesis of HD.

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The Role of 5-HT1B/1D Receptors in the Treatment of Migraine

CNS Spectrums ◽

10.1017/s1092852900006313 ◽

1998 ◽

Vol 3 (8) ◽

pp. 30-39 ◽

Cited By ~ 2

Author(s):

Christian Waeber

Keyword(s):

Sensory Neurons ◽

Rodent Models ◽

The One ◽

The Relationship

AbstractOf all known neurotransmitters, 5-HT is the one most frequently mentioned in the pathophysiology of migraine. This review focuses on the relationship between the efficacy of sumatriptan and other migraine agents and their effects on specific 5-HT receptors in rodent models. These agents are seen to have effects on vascular constriction and the release of vasoactive and inflammatory peptides from trigeminovascular sensory neurons. Specific subtypes of the 5-HT1 receptors appear to mediate these effects.

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Interstellar gas in the central region of the Galaxy

Symposium - International Astronomical Union ◽

10.1017/s0074180900101032 ◽

1967 ◽

Vol 31 ◽

pp. 239-251 ◽

Cited By ~ 3

Author(s):

F. J. Kerr

Keyword(s):

Central Region ◽

Galactic Plane ◽

Neutral Hydrogen ◽

Continuum Emission ◽

Galactic Centre ◽

Interstellar Gas ◽

Hydrogen Recombination ◽

The Galaxy ◽

Centre Region ◽

The Relationship

A review is given of information on the galactic-centre region obtained from recent observations of the 21-cm line from neutral hydrogen, the 18-cm group of OH lines, a hydrogen recombination line at 6 cm wavelength, and the continuum emission from ionized hydrogen.Both inward and outward motions are important in this region, in addition to rotation. Several types of observation indicate the presence of material in features inclined to the galactic plane. The relationship between the H and OH concentrations is not yet clear, but a rough picture of the central region can be proposed.

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The relationship of the scleractinian corals to the rugose corals

Paleobiology ◽

10.1017/s0094837300025707 ◽

1980 ◽

Vol 6 (02) ◽

pp. 146-160 ◽

Cited By ~ 29

Author(s):

William A. Oliver

Keyword(s):

Critical Points ◽

Scleractinian Corals ◽

Convincing Evidence ◽

Early Triassic ◽

Rugose Corals ◽

History Of ◽

The Subject ◽

Relationship Of ◽

The Relationship ◽

Biologic Factors

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.

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Choosing a Markov blanket

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002632 ◽

2020 ◽

Vol 43 ◽

Author(s):

Thomas Parr

Keyword(s):

Markov Blanket ◽

Target Article ◽

The Relationship

Abstract This commentary focuses upon the relationship between two themes in the target article: the ways in which a Markov blanket may be defined and the role of precision and salience in mediating the interactions between what is internal and external to a system. These each rest upon the different perspectives we might take while “choosing” a Markov blanket.

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