THE IMPACT OF P-GLYCOPROTEIN ON THE DISPOSITION OF DRUGS TARGETED FOR INDICATIONS OF THE CENTRAL NERVOUS SYSTEM: EVALUATION USING THE MDR1A/1B KNOCKOUT MOUSE MODEL

2004 ◽  
Vol 33 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Angela Doran ◽  
R. Scott Obach ◽  
Bill J. Smith ◽  
Natilie A. Hosea ◽  
Stacey Becker ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Knockout Mouse ◽  
System Evaluation ◽  
Knockout Mouse Model ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
The Impact

scholarly journals The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1372
Author(s):  
Tengrui Shi ◽  
Jianxi Song ◽  
Guanying You ◽  
Yujie Yang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Knockout Mouse Model ◽  
The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

scholarly journals Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System

2020 ◽  
Vol 37 (10) ◽  
Author(s):  
Manting Chiang ◽  
Hyun-moon Back ◽  
Jong Bong Lee ◽  
Sarah Oh ◽  
Tiffany Guo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pharmacokinetic Modeling ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
The Impact

scholarly journals MicroRNA-203 represses selection and expansion of oncogenic Hras transformed tumor initiating cells

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kent Riemondy ◽  
Xiao-jing Wang ◽  
Enrique C Torchia ◽  
Dennis R Roop ◽  
Rui Yi
Keyword(s):  
Cell Division ◽  
Skin Cancer ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Selection Process ◽  
Tumor Initiating Cells ◽  
Knockout Mouse Model ◽  
Active Selection ◽  
The Impact

In many mouse models of skin cancer, only a few tumors typically form even though many cells competent for tumorigenesis receive the same oncogenic stimuli. These observations suggest an active selection process for tumor-initiating cells. Here, we use quantitative mRNA- and miR-Seq to determine the impact of HrasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HrasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 using an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for Hras-initiated tumorigenesis. These targets include critical regulators of the Ras pathway and essential genes required for cell division. This study establishes a role for the loss of microRNA-203 in promoting selection and expansion of Hras mutated cells and identifies a mechanism through which microRNA-203 antagonizes Hras-mediated tumorigenesis.

scholarly journals The variable monoaminergic outcomes of cleaner fish brains when facing different social and mutualistic contexts

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4830 ◽  
Author(s):  
Murilo S. de Abreu ◽  
João P.M. Messias ◽  
Per-Ove Thörnqvist ◽  
Svante Winberg ◽  
Marta C. Soares
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Behaviour ◽  
Visual Assessment ◽  
Physical Contact ◽  
Specific Response ◽  
Dopaminergic Activity ◽  
Cleaner Fish ◽  
The Central Nervous System ◽  
The Impact

The monoamines serotonin and dopamine are important neuromodulators present in the central nervous system, known to be active regulators of social behaviour in fish as in other vertebrates. Our aim was to investigate the region-specific brain monoaminergic differences arising when individual cleaners face a client (mutualistic context) compared to when they are introduced to another conspecific (conspecific context), and to understand the relevance of visual assessment compared to the impact of physical contact with any partner. We demonstrated that serotoninergic activity at the diencephalon responds mostly to the absence of physical contact with clients whereas cerebellar dopaminergic activity responds to actual cleaning engagement. We provide first insights on the brain’s monoaminergic (region-specific) response variations, involved in the expression of cleaner fishes’ mutualistic and conspecific behaviour. These results contribute to a better understanding of the monoaminergic activity in accordance to different socio-behavioural contexts.

scholarly journals Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

2021 ◽  
Vol 11 ◽  
Author(s):  
Lintao Wang ◽  
Zhiguang Ren ◽  
Li Ma ◽  
Yanjie Han ◽  
Wenqiang Wei ◽  
...  
Keyword(s):  
Public Health ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Diseases ◽  
Public Health Problem ◽  
Neurological Complications ◽  
Major Public Health Problem ◽  
The Central Nervous System ◽  
The Impact ◽  
Great Harm

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

scholarly journals Endogenous Cu in the central nervous system fails to satiate the elevated requirement for Cu in a mutant SOD1 mouse model of ALS

Metallomics ◽  
2016 ◽  
Vol 8 (9) ◽  
pp. 1002-1011 ◽  
Author(s):  
J. B. Hilton ◽  
A. R. White ◽  
P. J. Crouch
Keyword(s):  
Central Nervous System ◽  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Mouse Model ◽  
Limited Capacity ◽  
Mutant Sod1 ◽  
The Central Nervous System ◽  
Sod1 Mouse ◽  
Lateral Sclerosis

It is unclear why ubiquitous expression of mutant SOD1 selectively affects the central nervous system in amyotrophic lateral sclerosis. Here we hypothesise that the central nervous system is primarily affected because, unlike other tissues, it has relatively limited capacity to satiate an increased requirement for Cu.

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Onur Akın ◽  
İbrahim Eker ◽  
Mutluay Arslan ◽  
Süleyman Tolga Yavuz ◽  
Sevil Akman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Central Nervous System ◽  
Nervous System ◽  
Healthy Children ◽  
Model Assessment ◽  
Obese Children ◽  
Neurocognitive Functions ◽  
The Central Nervous System ◽  
Biochemical Indices ◽  
The Impact

AbstractBackground:Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children.Methods:Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups.Results:Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IR– groups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessment-insulin resistance (HOMA-IR) values. EEGs showed significantly more frequent ‘slowing during hyperventilation’ (SDHs) in obese children than non-obese children.Conclusions:Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR. An early examination of cognitive functions may help identify and correct such abnormalities in obese children.

HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

2010 ◽  
Vol 16 (10) ◽  
pp. 1173-1177 ◽  
Author(s):  
M. Shahbazi ◽  
H. Ebadi ◽  
D. Fathi ◽  
D. Roshandel ◽  
M. Mohamadhosseni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Promoter Polymorphism ◽  
Exact Test ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Pcr Method ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

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