A genetic mouse model of adult-onset, pervasive central nervous system demyelination with robust remyelination

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.

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Microglia control small vessel calcification via TREM2

Science Advances ◽

10.1126/sciadv.abc4898 ◽

2021 ◽

Vol 7 (9) ◽

pp. eabc4898

Author(s):

Yvette Zarb ◽

Sucheta Sridhar ◽

Sina Nassiri ◽

Sebastian Guido Utz ◽

Johanna Schaffenrath ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mouse Model ◽

Vascular Calcification ◽

Neurovascular Unit ◽

Small Vessel ◽

Vascular Pathology ◽

Cns Development ◽

Brain Calcification

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

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Omega-3 Index, fish consumption, use of fish oil supplements and first clinical diagnosis of central nervous system demyelination

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2021.103210 ◽

2021 ◽

pp. 103210

Author(s):

Alison Daly ◽

Christopher Martin ◽

Jill Sherriff ◽

Trevor A Mori ◽

Gavin Pereira ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Fish Oil ◽

Clinical Diagnosis ◽

Fish Consumption ◽

Omega 3 ◽

Central Nervous System Demyelination

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A neonatal mouse model of central nervous system infections caused by Coxsackievirus B5

Emerging Microbes & Infections ◽

10.1038/s41426-018-0186-y ◽

2018 ◽

Vol 7 (1) ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Qunying Mao ◽

Xiaotian Hao ◽

Yalin Hu ◽

Ruixiao Du ◽

Shuhui Lang ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mouse Model ◽

Neonatal Mouse ◽

Central Nervous System Infections

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Stress response in the central nervous system of a transgenic mouse model of bovine spongiform encephalopathy

The Veterinary Journal ◽

10.1016/j.tvjl.2007.06.002 ◽

2008 ◽

Vol 178 (1) ◽

pp. 126-129 ◽

Cited By ~ 11

Author(s):

Raül Tortosa ◽

Enric Vidal ◽

Carme Costa ◽

Elia Alamillo ◽

Juan Maria Torres ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Stress Response ◽

Mouse Model ◽

Bovine Spongiform Encephalopathy ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Spongiform Encephalopathy ◽

The Central Nervous System

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Morbillivirus Infection of the Mouse Central Nervous System Induces Region-Specific Upregulation of MMPs and TIMPs Correlated to Inflammatory Cytokine Expression

Journal of Virology ◽

10.1128/jvi.75.17.8268-8282.2001 ◽

2001 ◽

Vol 75 (17) ◽

pp. 8268-8282 ◽

Cited By ~ 36

Author(s):

Seng-Thuon Khuth ◽

Hideo Akaoka ◽

Axel Pagenstecher ◽

Olivier Verlaeten ◽

Marie-Françoise Belin ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mouse Model ◽

Neurological Disorders ◽

Dynamic Balance ◽

Brain Structures ◽

Cytokine Expression ◽

Tissue Inhibitors Of Metalloproteinases ◽

Cns Infection ◽

Necrosis Factor Alpha

ABSTRACT Viral infection of the central nervous system (CNS) can result in perturbation of cell-to-cell communication involving the extracellular matrix (ECM). ECM integrity is maintained by a dynamic balance between the synthesis and proteolysis of its components, mainly as a result of the action of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). An MMP/TIMP imbalance may be critical in triggering neurological disorders, in particular in virally induced neural disorders. In the present study, a mouse model of brain infection using a neurotropic strain of canine distemper virus (CDV) was used to study the effect of CNS infection on the MMP/TIMP balance and cytokine expression. CDV replicates almost exclusively in neurons and has a unique pattern of expression (cortex, hypothalamus, monoaminergic nuclei, hippocampus, and spinal cord). Here we show that although several mouse brain structures were infected, they exhibited a differential pattern in terms of MMP, TIMP, and cytokine expression, exemplified by (i) a large increase in pro-MMP9 levels, in particular in the hippocampus, which occurred mainly in neurons and was associated with in situ gelatinolytic activity, (ii) specific and significant upregulation of MT1-MMP mRNA expression in the cortex and hypothalamus, (iii) an MMP/TIMP imbalance, suggested by the upregulation of TIMP-1 mRNA in the cortex, hippocampus, and hypothalamus and of TIMP-3 mRNA in the cortex, and (iv) a concomitant region-specific large increase in expression of Th1-like cytokines, such as gamma interferon, tumor necrosis factor alpha, and interleukin 6 (IL-6), contrasting with weaker induction of Th2-like cytokines, such as IL-4 and IL-10. These data indicate that an MMP/TIMP imbalance in specific brain structures, which is tightly associated with a local inflammatory process as shown by the presence of immune infiltrating cells, differentially impairs CNS integrity and may contribute to the multiplicity of late neurological disorders observed in this viral mouse model.

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