scholarly journals Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages, Alters Metabolic Pathways, and Elevates Cell Death Pathways: A Single-Cell Analysis

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1297
Author(s):  
Meng Niu ◽  
Brenda Morsey ◽  
Benjamin G. Lamberty ◽  
Katy Emanuel ◽  
Fang Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Hiv Infection ◽  
Single Cell ◽  
Metabolic Pathways ◽  
Drugs Of Abuse ◽  
Expression Patterns ◽  
Cns Infection ◽  
Brain Macrophages ◽  
Cell Death Pathways ◽  
The Brain

Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.

scholarly journals Alternative Cell Death Pathways and Cell Metabolism

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Simone Fulda
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Mammalian Cells ◽  
Cell Metabolism ◽  
Environmental Cues ◽  
Cell Death Pathways ◽  
Mitochondrial Signaling ◽  
Transduction Mechanisms ◽  
Cell Death Signaling ◽  
Critical Components

While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases.

scholarly journals Altering cell death pathways as an approach to cure HIV infection

2013 ◽  
Vol 4 (7) ◽  
pp. e718-e718 ◽  
Author(s):  
A D Badley ◽  
A Sainski ◽  
F Wightman ◽  
S R Lewin
Keyword(s):  
Cell Death ◽  
Hiv Infection ◽  
Cell Death Pathways

scholarly journals A gut feeling about stroke reveals gut-brain axis’ active role in homeostasis and dysbiosis

2020 ◽  
Vol 40 (5) ◽  
pp. 1132-1134 ◽  
Author(s):  
Brooke Bonsack ◽  
Rays HY Jiang ◽  
Cesar V Borlongan
Keyword(s):  
Cell Death ◽  
Regenerative Medicine ◽  
Neurological Disorders ◽  
Paradigm Shift ◽  
Potential Application ◽  
Inflammatory Responses ◽  
Active Role ◽  
Cell Death Pathways ◽  
Therapeutic Outcomes ◽  
The Brain

Peripheral inflammatory responses accompany many neurological disorders, including stroke. The gut-brain axis opens new avenues in our understanding of stroke progression and abrogation of secondary cell death. Certain microbiomes, especially those related to inflammation, appear to closely reflect the homeostasis and dysbiosis of both the brain and the gut, suggesting their potential application as biomarkers and therapeutic targets. A paradigm shift from purely central towards incorporating peripheral sequestration of cell death pathways may improve stroke therapeutic outcomes. Recognizing this gut-brain axis as key to disease pathology and treatment is likely to usher innovative approaches in cell-based regenerative medicine for stroke.

scholarly journals Characterization of the brain functional architecture of psychostimulant withdrawal using single-cell whole brain imaging

2019 ◽  
Author(s):  
Adam Kimbrough ◽  
Lauren C. Smith ◽  
Marsida Kallupi ◽  
Sierra Simpson ◽  
Andres Collazo ◽  
...  
Keyword(s):  
Single Cell ◽  
Brain Imaging ◽  
Drugs Of Abuse ◽  
Brain Regions ◽  
Functional Architecture ◽  
Whole Brain ◽  
Similarities And Differences ◽  
Drug Dependent ◽  
The Brain

AbstractNumerous brain regions have been identified as contributing to addiction-like behaviors, but unclear is the way in which these brain regions as a whole lead to addiction. The search for a final common brain pathway that is involved in addiction remains elusive. To address this question, we used male C57BL/6J mice and performed single-cell whole-brain imaging of neural activity during withdrawal from cocaine, methamphetamine, and nicotine. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modularity, with a shift from a cortical- to subcortical-driven network, including a decrease in total hub brain regions. These results demonstrate that psychostimulant withdrawal produces the drug-dependent remodeling of functional architecture of the brain and suggest that the decreased modularity of brain functional networks and not a specific set of brain regions may represent the final common pathway that leads to addiction.Significance StatementA key aspect of treating drug abuse is understanding similarities and differences of how drugs of abuse affect the brain. In the present study we examined how the brain is altered during withdrawal from psychostimulants. We found that each drug produced a unique pattern of activity in the brain, but that brains in withdrawal from cocaine and methamphetamine shared similar features. Interestingly, we found the major common link between withdrawal from all psychostimulants, when compared to controls, was a shift in the broad organization of the brain in the form of reduced modularity. Reduced modularity has been shown in several brain disorders, including traumatic brain injury, and dementia, and may be the common link between drugs of abuse.

Development and Challenges of Nanotherapeutic Formulations for Targeting Mitochondrial Cell Death Pathways in Lung and Brain Degenerative Diseases

2020 ◽  
Vol 48 (3) ◽  
pp. 137-152
Author(s):  
Marko Manevski ◽  
Dinesh Devadoss ◽  
Ruben Castro ◽  
Lauren Delatorre ◽  
Adriana Yndart ◽  
...  
Keyword(s):  
Cell Death ◽  
Degenerative Diseases ◽  
Cell Death Pathways

Biological response of the organism to the introduction of metal nanocomposites

2020 ◽  
pp. 761-762
Author(s):  
L. M. Sosedova ◽  
V. S. Rukavishnikov ◽  
E. A. Titov
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Biological Response ◽  
Brain Cell ◽  
Metal Nanocomposites ◽  
The Brain

The results of a study on rats toxicity of nanoparticles of metals bismuth, gadolinium and silver encapsulated in a natural biopolymer matrix arabinogalactan are presented. When intake of nanocomposite of silver revealed the readiness of the brain cell to apoptosis. The effect of bismuth and gadolinium nanocomposites did not cause an increase in the process of programmed cell death.

Neurometabolic Diseases in Children: Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Features

2019 ◽  
Vol 15 (3) ◽  
pp. 255-268
Author(s):  
Direnç Özlem Aksoy ◽  
Alpay Alkan
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Metabolic Pathways ◽  
Wide Spectrum ◽  
Demyelinating Diseases ◽  
Resonance Spectroscopy ◽  
Resonance Imaging ◽  
Neurometabolic Disorders ◽  
Brain Involvement ◽  
The Brain

Background: Neurometabolic diseases are a group of diseases secondary to disorders in different metabolic pathways, which lead to white and/or gray matter of the brain involvement. </P><P> Discussion: Neurometabolic disorders are divided in two groups as dysmyelinating and demyelinating diseases. Because of wide spectrum of these disorders, there are many different classifications of neurometabolic diseases. We used the classification according to brain involvement areas. In radiological evaluation, MRI provides useful information for these disseases. Conclusion: Magnetic Resonance Spectroscopy (MRS) provides additional metabolic information for diagnosis and follow ups in childhood with neurometabolic diseases.

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