Longitudinal Characterization of the Brain Proteomes for the Tg2576 Amyloid Mouse Model Using Shotgun Based Mass Spectrometry

2012 ◽  
Vol 11 (12) ◽  
pp. 6159-6174 ◽  
Author(s):  
Ganna Shevchenko ◽  
Magnus Wetterhall ◽  
Jonas Bergquist ◽  
Kina Höglund ◽  
Lars I. Andersson ◽  
...  
2021 ◽  
Author(s):  
Amal Yousfan ◽  
Noelia Rubio Carrero ◽  
Mohamad Al-Ali ◽  
Abdul Hakim Nattouf ◽  
Houmam Kafa

In this work we describe the preparation and characterization of lecithin-chitosan nanoparticles (L10Ci+), and investigate their ability to deliver the anti-epileptic drug phenytoin (PHT) to mouse brain following intranasal (IN)...


Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 185 ◽  
Author(s):  
Kosuke Saito ◽  
Kotaro Hattori ◽  
Tomohiro Andou ◽  
Yoshinori Satomi ◽  
Masamitsu Gotou ◽  
...  

Cerebrospinal fluid (CSF) metabolites reflect biochemical diffusion/export from the brain and possibly serve as biomarkers related to brain disease severity, pathophysiology, and therapeutic efficacy/toxicity. Metabolomic studies using blood matrices have demonstrated interindividual and preanalytical variation of blood metabolites, whereas those of CSF metabolites remain unclear. In this study, we aimed to delineate the postprandial effects on CSF metabolites because fasting of patients with brain-related disorders is challenging. We collected pre- and postprandial (1.5, 3, and 6 h) plasma and CSF from nine healthy subjects. Using a mass-spectrometry-based global metabolomics approach, 150 and 130 hydrophilic metabolites and 263 and 340 lipids were detected in CSF and plasma, respectively. Principal component analysis of CSF hydrophilic metabolites and lipids primarily classified individual subjects at any time point, suggesting that the postprandial effects had a lower impact than interindividual variations on CSF metabolites. Individually, less than 10% of the CSF metabolites were putatively altered by postprandial effects (with either significant differences or over 2-fold changes, but not both) at any time point. Thus, global CSF metabolite levels are not directly associated with food intake, and except for several putatively altered CSF metabolites, postprandial effects are not a major concern when applying CSF metabolomics to screen biomarkers.


2019 ◽  
Author(s):  
Lukasz Piszczek ◽  
Simone Memoli ◽  
Angelo Raggioli ◽  
José Viosca ◽  
Jeanette Rientjes ◽  
...  

AbstractGenetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioural traits we set out to develop a mouse model of the human 5-HTT- LPR. Here we describe the creation and characterization of a set of mouse lines with single copy human transgenes carrying the short and long 5-HTT-LPR variants.


2019 ◽  
Vol 15 ◽  
pp. P1297-P1297
Author(s):  
Jukka Puoliväli ◽  
Juho Oksman ◽  
Kimmo Lehtimäki ◽  
Tuulia Huhtala ◽  
Jussi Rytkönen ◽  
...  

Author(s):  
Aarti Tripathi ◽  
Arup Banerjee ◽  
Sudhanshu Vrati

A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3-4 weeks old C57BL/6 mice. The blood-brain barrier leakage was evident in JEV-S3 infected mice, where viral antigens and RNA were consistently demonstrated in the brain and infiltration of activated immune cells as evidenced by an increased level of CD45+CD11b+ cell population. Histopathology studies showed the presence of perivascular cuffing, haemorrhage and necrotic foci in the virus-infected brain conforming to the pathological changes seen in the brain of JEV-infected patients. Mass spectrometry studies characterized the molecular events leading to brain inflammation in the infected mice. Notably, a significant induction of inflammatory cytokines such as IFN-γ, Il-6, TNF-α, and TGF-β was observed. Further, genome sequencing of the JEV-S3 isolate identified the mutations selected during the mouse passage of the virus. Overall, we present an in-depth characterization of a robust and reproducible mouse model of JEV infection. The JEV-S3 isolate will be a useful tool to screen antivirals and study the virus pathogenesis in the adolescent mouse model.


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