scholarly journals Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease

2015 ◽  
Vol 291 (4) ◽  
pp. 1905-1920 ◽  
Author(s):  
Brian Spencer ◽  
Rewati Potkar ◽  
Jeff Metcalf ◽  
Ivy Thrin ◽  
Anthony Adame ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Neuropeptide Y ◽  
Targeted Delivery ◽  
Lentiviral Vector ◽  
Receptor Expression ◽  
Neural Precursor ◽  
The Central Nervous System

Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of Aβ. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with Aβ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-Aβ therapeutic.

scholarly journals Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

10.1038/78682 ◽  
2000 ◽  
Vol 6 (8) ◽  
pp. 916-919 ◽  
Author(s):  
Frédérique Bard ◽  
Catherine Cannon ◽  
Robin Barbour ◽  
Rae-Lyn Burke ◽  
Dora Games ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
The Central Nervous System

The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

2019 ◽  
Vol 20 (7) ◽  
pp. 750-758 ◽  
Author(s):  
Yi Wu ◽  
Hengxun He ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropeptide Y ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
Vital Role ◽  
Gut Peptides ◽  
Nonalcoholic Fatty Liver ◽  
The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

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 Promising Nanotechnology Approaches in Treatment of Autoimmune Diseases of Central Nervous System

2020 ◽  
Vol 10 (6) ◽  
pp. 338 ◽  
Author(s):  
Maria Chountoulesi ◽  
Costas Demetzos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Delivery ◽  
Current Treatment ◽  
Autoimmune Encephalomyelitis ◽  
Axon Damage ◽  
The Central Nervous System ◽  
Therapeutic Tools ◽  
High Bioavailability ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic, autoimmune, neurodegenerative disease of the central nervous system (CNS) that yields to neuronal axon damage, demyelization, and paralysis. Although several drugs were designed for the treatment of MS, with some of them being approved in the last few decades, the complete remission and the treatment of progressive forms still remain a matter of debate and a medical challenge. Nanotechnology provides a variety of promising therapeutic tools that can be applied for the treatment of MS, overcoming the barriers and the limitations of the already existing immunosuppressive and biological therapies. In the present review, we explore literature case studies on the development of drug delivery nanosystems for the targeted delivery of MS drugs in the pathological tissues of the CNS, providing high bioavailability and enhanced therapeutic efficiency, as well as nanosystems for the delivery of agents to facilitate efficient remyelination. Moreover, we present examples of tolerance-inducing nanocarriers, being used as promising vaccines for antigen-specific immunotherapy of MS. We emphasize on liposomes, as well as lipid- and polymer-based nanoparticles. Finally, we highlight the future perspectives given by the nanotechnology field toward the improvement of the current treatment of MS and its animal model, experimental autoimmune encephalomyelitis (EAE).

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.

scholarly journals A Japanese Encephalitis Virus Genotype 5 Molecular Clone Is Highly Neuropathogenic in a Mouse Model: Impact of the Structural Protein Region on Virulence

2015 ◽  
Vol 89 (11) ◽  
pp. 5862-5875 ◽  
Author(s):  
Mélissanne de Wispelaere ◽  
Marie-Pascale Frenkiel ◽  
Philippe Desprès
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Viral Clearance ◽  
The Central Nervous System ◽  
Genotype 5

ABSTRACTJapanese encephalitis virus (JEV) strains can be separated into 5 genotypes (g1 to g5) based on sequence similarity. JEV g5 strains have been rarely isolated and are poorly characterized. We report here the full characterization of a g5 virus generated using a cDNA-based technology and its comparison with a widely studied g3 strain. We did not observe any major differences between those viruses when their infectious cycles were studied in various cell linesin vitro. Interestingly, the JEV g5 strain was highly pathogenic when inoculated to BALB/c mice, which are known to be largely resistant to JEV g3 infection. The study of chimeric viruses between JEV g3 and g5 showed that there was a poor viral clearance of viruses that express JEV g5 structural proteins in BALB/c mice blood, which correlated with viral invasion of the central nervous system and encephalitis. In addition, using anin vitromodel of the blood-brain barrier, we were able to show that JEV g5 does not have an enhanced capacity for entering the central nervous system, compared to JEV g3. Overall, in addition to providing a first characterization of the understudied JEV g5, our work highlights the importance of sustaining an early viremia in the development of JEV encephalitis.IMPORTANCEGenotype 5 viruses are genetically and serologically distinct from other JEV genotypes and can been associated with human encephalitis, which warrants the need for their characterization. In this study, we characterized thein vitroandin vivoproperties of a JEV g5 strain and showed that it was more neuropathogenic in a mouse model than a well-characterized JEV g3 strain. The enhanced virulence of JEV g5 was associated with poor viral clearance but not with enhanced crossing of the blood-brain barrier, thus providing new insights into JEV pathogenesis.

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