Evidence of neuronal degeneration in C57Bl/6 mice infected with the LP-BM5 leukemia retrovirus mixture

: Alzheimer’s disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically it is described by cognitive impairment, and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of the AD in recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities such as anti-amyloidogenic, anticholinesterase, and antioxidant. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.

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Diabetes, Diabetic Complications, and Phosphate Toxicity: A Scoping Review

Current Diabetes Reviews ◽

10.2174/1573399815666191104113236 ◽

2020 ◽

Vol 16 (7) ◽

pp. 674-689 ◽

Cited By ~ 4

Author(s):

Ronald B. Brown

Keyword(s):

Scoping Review ◽

Diabetic Complications ◽

Inorganic Phosphate ◽

Dietary Intervention ◽

Neuronal Degeneration ◽

Ectopic Calcification ◽

Treatment And Prevention ◽

Research Findings ◽

Serum Inorganic Phosphate ◽

Prevention Of Diabetes

This article presents a scoping review and synthesis of research findings investigating the toxic cellular accumulation of dysregulated inorganic phosphate—phosphate toxicity—as a pathophysiological determinant of diabetes and diabetic complications. Phosphorus, an essential micronutrient, is closely linked to the cellular metabolism of glucose for energy production, and serum inorganic phosphate is often transported into cells along with glucose during insulin therapy. Mitochondrial dysfunction and apoptosis, endoplasmic reticulum stress, neuronal degeneration, and pancreatic cancer are associated with dysregulated levels of phosphate in diabetes. Ectopic calcification involving deposition of calcium-phosphate crystals is prevalent throughout diabetic complications, including vascular calcification, nephropathy, retinopathy, and bone disorders. A low-glycemic, low-phosphate dietary intervention is proposed for further investigations in the treatment and prevention of diabetes and related diabetic pathologies.

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Functional Characterization of the Adenylyl Cyclase Genesgs-1by Analysis of a Mutational Spectrum inCaenorhabditis elegans

Genetics ◽

10.1093/genetics/161.1.133 ◽

2002 ◽

Vol 161 (1) ◽

pp. 133-142 ◽

Cited By ~ 4

Author(s):

Celine Moorman ◽

Ronald H A Plasterk

Keyword(s):

Life Span ◽

Adenylyl Cyclase ◽

Neuronal Degeneration ◽

Functional Characterization ◽

Adenylyl Cyclases ◽

Loss Of Function ◽

C Elegans ◽

Larval Stages ◽

Pharyngeal Pumping

AbstractThe sgs-1 (suppressor of activated Gαs) gene encodes one of the four adenylyl cyclases in the nematode C. elegans and is most similar to mammalian adenylyl cyclase type IX. We isolated a complete loss-of-function mutation in sgs-1 and found it to result in animals with retarded development that arrest in variable larval stages. sgs-1 mutant animals exhibit lethargic movement and pharyngeal pumping and (while not reaching adulthood) have a mean life span that is >50% extended compared to wild type. An extensive set of reduction-of-function mutations in sgs-1 was isolated in a screen for suppressors of a neuronal degeneration phenotype induced by the expression of a constitutively active version of the heterotrimeric Gαs subunit of C. elegans. Although most of these mutations change conserved residues within the catalytic domains of sgs-1, mutations in the less-conserved transmembrane domains are also found. The sgs-1 reduction-of-function mutants are viable and have reduced locomotion rates, but do not show defects in pharyngeal pumping or life span.

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Effect of Yuzu (Citrus junos) Seed Limonoids and Spermine on Intestinal Microbiota and Hypothalamic Tissue in the Sandhoff Disease Mouse Model

Medical Sciences ◽

10.3390/medsci9010017 ◽

2021 ◽

Vol 9 (1) ◽

pp. 17

Author(s):

Mayumi Minamisawa ◽

Takuma Suzumura ◽

Sudeep Bose ◽

Tetsuyuki Taniai ◽

Gota Kawai ◽

...

Keyword(s):

Mouse Model ◽

Intestinal Microbiota ◽

Neuronal Degeneration ◽

Sandhoff Disease ◽

Short Chain Fatty Acids ◽

Rrna Gene ◽

Wild Type ◽

Degrading Bacteria ◽

Citrus Junos ◽

Hypothalamic Tissue

The effect of limonoids and spermine (Spm) extracted from yuzu (Citrus junos) seeds on the gut and the brain in a mouse model with Sandhoff disease (SD) was investigated. Wild-type and SD mice were fed a normal diet, or a diet supplemented with limonoid, Spm, or limonoid + Spm for 14–18 weeks, and then 16S rRNA gene amplicon sequencing with extracted DNA from their feces was executed. For SD control mice, intestinal microbiota was mostly composed of Lactobacillus and linked to dysbiosis. For SD and wild-type mice fed with limonoids + Spm or limonoids alone, intestinal microbiota was rich in mucin-degrading bacteria, including Bacteroidetes, Verrucomicrobia, and Firmicutes, and displayed a higher production of short-chain fatty acids and immunoglobulin A. Additionally, SD mice fed with limonoids + Spm or limonoids alone had less inflammation in hypothalamic tissues and displayed a greater number of neurons. Administration of limonoids and/or Spm improved the proportions of beneficial intestinal microbiota to host health and reduced neuronal degeneration in SD mice. Yuzu seed limonoids and Spermine may help to maintain the homeostasis of intestinal microbiota and hypothalamic tissue in the SD mouse model.

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Diffusion tensor imaging analysis in scrub typhus meningoencephalitis to determine the alteration of microstructural subcortical white-matter integrity

The Neuroradiology Journal ◽

10.1177/1971400920980311 ◽

2020 ◽

pp. 197140092098031

Author(s):

Pranjal Phukan ◽

Kalyan Sarma ◽

Aman Yusuf Khan ◽

Bhupen Barman ◽

Md Jamil ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Scrub Typhus ◽

Diffusion Tensor ◽

Neuronal Degeneration ◽

Central Nervous System Involvement ◽

Subcortical White Matter ◽

White Matter Integrity ◽

Conventional Mri ◽

Significant Difference

Background and purpose Magnetic resonance imaging (MRI) of the brain in scrub typhus meningoencephalitis is non-specific, and in the majority of the cases, conventional MRI fails to detect any abnormality. However, autopsy reports depict central nervous system involvement in almost all patients. There is therefore a need for research on the quantitative assessment of brain parenchyma that can detect microstructural abnormalities. The study aimed to assess the microstructural integrity changes of scrub typhus meningoencephalitis by using different diffusion tensor imaging (DTI) parameters. Methods This was a retrospective analysis of scrub typhus meningoencephalitis. Seven patients and seven age- and sex-matched healthy controls were included. Different DTI parameters such as apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), trace, volume ratio (VR) and geodesic anisotropy (GA) were obtained from six different regions of subcortical white matter at the level of the centrum semiovale. Intergroup significant difference was determined by one-way analysis of variance followed by Tukey’s post hoc test. Receiver operating characteristic curves were constructed to determine the accuracy of the DTI matrices. Results There was a significant decrease in FA, RA and GA as well as an increase in ADC and VR in the subcortical white matter in patients with scrub typhus meningoencephalitis compared to controls ( p < 0.001). The maximum sensitivity of the DTI parameters was 85.7%, and the maximum specificity was 81%. Conclusion There was an alteration of subcortical white-matter integrity in scrub typhus meningoencephalitis that represents the axonal degeneration, myelin breakdown and neuronal degeneration. DTI may be a useful tool to detect white-matter abnormalities in scrub typhus meningoencephalitis in clinical practice, particularly in patients with negative conventional MRI.

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