scholarly journals An open-source pipeline for analysing changes in microglial morphology

Open Biology ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 210045
Author(s):  
Devin Clarke ◽  
Hans S. Crombag ◽  
Catherine N. Hall
Keyword(s):  
Dimensionality Reduction ◽  
Open Source ◽  
High Fat Diet ◽  
Training Data ◽  
Morphology Analysis ◽  
Inflammatory State ◽  
Microglial Morphology ◽  
Automated Image Processing ◽  
The Brain ◽  
Microglia Morphology

Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters describing microglial morphology. It then compares control and ‘inflammation’ training data and uses dimensionality reduction to generate a single metric of morphological change (an ‘inflammation index’). This index can then be calculated for test data to assess inflammation, as we demonstrate by investigating the effect of short-term high-fat diet consumption in heterozygous Cx3CR1-GFP mice, finding no significant effects of diet. Our pipeline represents the first open-source microglia morphology pipeline combining semi-automated image processing and dimensionality reduction. It uses free software (ImageJ and R) and can be applied to a wide variety of experimental paradigms. We anticipate it will enable others to more easily take advantage of the powerful insights microglial morphology analysis provides.

scholarly journals An Open-Source Pipeline for Analyzing Changes In Microglial Morphology

2021 ◽  
Author(s):  
Devin Clarke ◽  
Hans S. Crombag ◽  
Catherine N. Hall
Keyword(s):  
Dimensionality Reduction ◽  
Open Source ◽  
High Fat Diet ◽  
Training Data ◽  
Morphology Analysis ◽  
Inflammatory State ◽  
Microglial Morphology ◽  
Automated Image Processing ◽  
The Brain ◽  
Microglia Morphology

ABSTRACTChanges in microglial morphology are powerful indicators of the inflammatory state of the brain. Here we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters describing microglial morphology. It then compares control and “inflammation” training data and uses dimensionality reduction to generate a single metric of morphological change (an ‘inflammation index’). This index can then be calculated for test data to assess inflammation, as we demonstrate by investigating the effect of short-term high fat diet consumption in heterozygous Cx3CR1-GFP mice, finding no significant effects of diet. Our pipeline represents the first open-source microglia morphology pipeline combining semi-automated image processing and dimensionality reduction. It uses free software (ImageJ and R) and can be applied to a wide variety of experimental paradigms. We anticipate it will enable others to more easily take advantage of the powerful insights microglial morphology analysis provides.

scholarly journals High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

2021 ◽  
Vol 22 (7) ◽  
pp. 3746
Author(s):  
Ilaria Zuliani ◽  
Chiara Lanzillotta ◽  
Antonella Tramutola ◽  
Eugenio Barone ◽  
Marzia Perluigi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Mitochondrial Activity ◽  
High Fat ◽  
Hexosamine Biosynthetic Pathway ◽  
Neurodegenerative Process ◽  
The Brain

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

scholarly journals Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun Lim ◽  
Seolsong Kim ◽  
Eun-Kyoung Kim
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Fat ◽  
Selective Autophagy ◽  
Induced Stress ◽  
Hypothalamic Cells ◽  
The Brain ◽  
Main Region

AbstractPalmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism. Interestingly, hypothalamic palmitate level is also increased under starvation, urging the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, we show that ER-phagy (ER-targeted selective autophagy) is required for progress of ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that, unlike the induction of ER stress under nutrient-rich conditions, palmitate protects hypothalamic cells from starvation-induced stress by inhibiting ER-phagy.

scholarly journals Effect of selective expression of dominant-negative PPARγ in pro-opiomelanocortin neurons on the control of energy balance

2016 ◽  
Vol 48 (7) ◽  
pp. 491-501 ◽  
Author(s):  
Madeliene Stump ◽  
Deng-Fu Guo ◽  
Ko-Ting Lu ◽  
Masashi Mukohda ◽  
Xuebo Liu ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
High Fat Diet ◽  
Control Diet ◽  
Cre Recombinase ◽  
Dominant Negative ◽  
High Fat ◽  
Pparγ Agonist ◽  
The Brain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

scholarly journals The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Kira V. Derkach ◽  
Vera M. Bondareva ◽  
Oxana V. Chistyakova ◽  
Lev M. Berstein ◽  
Alexander O. Shpakov
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Brain Serotonin ◽  
Serotonin Level ◽  
High Fat ◽  
Brain Serotonin Level ◽  
The Brain

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation byβ-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

scholarly journals Generalization-Based Acquisition of Training Data for Motor Primitive Learning by Neural Networks

2021 ◽  
Vol 11 (3) ◽  
pp. 1013
Author(s):  
Zvezdan Lončarević ◽  
Rok Pahič ◽  
Aleš Ude ◽  
Andrej Gams
Keyword(s):  
Neural Networks ◽  
Dimensionality Reduction ◽  
Gaussian Process Regression ◽  
Search Space ◽  
Robot Learning ◽  
Training Data ◽  
Practical Applications ◽  
Latent Space ◽  
Real Robot ◽  
Low Dimensional

Autonomous robot learning in unstructured environments often faces the problem that the dimensionality of the search space is too large for practical applications. Dimensionality reduction techniques have been developed to address this problem and describe motor skills in low-dimensional latent spaces. Most of these techniques require the availability of a sufficiently large database of example task executions to compute the latent space. However, the generation of many example task executions on a real robot is tedious, and prone to errors and equipment failures. The main result of this paper is a new approach for efficient database gathering by performing a small number of task executions with a real robot and applying statistical generalization, e.g., Gaussian process regression, to generate more data. We have shown in our experiments that the data generated this way can be used for dimensionality reduction with autoencoder neural networks. The resulting latent spaces can be exploited to implement robot learning more efficiently. The proposed approach has been evaluated on the problem of robotic throwing at a target. Simulation and real-world results with a humanoid robot TALOS are provided. They confirm the effectiveness of generalization-based database acquisition and the efficiency of learning in a low-dimensional latent space.

Involvement of Nuclear Related Factor 2 Signaling Pathway in the Brain of Obese Rats and Obesity-Resistant Rats Induced by High-Fat Diet

2016 ◽  
Vol 19 (4) ◽  
pp. 404-409 ◽  
Author(s):  
Wei-Wei Ma ◽  
Bing-Jie Ding ◽  
Li-Jing Wang ◽  
Yi Shao ◽  
Rong Xiao
Keyword(s):  
Signaling Pathway ◽  
High Fat Diet ◽  
Related Factor ◽  
High Fat ◽  
Obese Rats ◽  
The Brain
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