Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

Download Full-text

Meningitis Caused by Salmonella Newport in a Five-Year-Old Child

Case Reports in Infectious Diseases ◽

10.1155/2016/2145805 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Ana De Malet ◽

Sheila Ingerto ◽

Israel Gañán

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Disorders ◽

Invasive Disease ◽

Salmonella Typhi ◽

Gram Negative ◽

Negative Bacillus ◽

Salmonella Newport ◽

Gram Negative Bacillus ◽

The Central Nervous System

Salmonella Newport is a Gram-negative bacillus belonging to the Enterobacteria family and the nontyphi Salmonella (NTS), usually related to gastroenteritis. Main difference between NTS and Salmonella typhi is that the last one evolves to an invasive disease easier than NTS. These can progress to bacteremias in around 5% of cases and secondary focuses can appear occasionally, as in meningitis. An infection of the central nervous system is uncommon, considering its incidence in 0.6–8% of the cases; most of them are described in developing countries and mainly in childhood, especially neonates. Bacterial meningitis by NTS mostly affects immunosuppressed people in Europe. Prognosis is adverse, with a 50% mortality rate, mainly due to complications of infection: hydrocephalus, ventriculitis, abscesses, subdural empyema, or stroke. Choice antibiotic treatments are cefotaxime, ceftriaxone, or ceftazidime. The aim of this paper is to present a case of meningitis caused by Salmonella Newport diagnosed in a five-year-old girl living in a rural area of the province of Ourense (Spain), with favorable evolution and without neurological disorders.

Download Full-text

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.

Download Full-text

Do Neurotrophins Connect Neurological Disorders and Heart Diseases?

Biomolecules ◽

10.3390/biom11111730 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1730

Author(s):

Masashi Fujitani ◽

Yoshinori Otani ◽

Hisao Miyajima

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cardiovascular Diseases ◽

Cardiac Dysfunction ◽

Neurological Disorders ◽

Direct Evidence ◽

Heart Diseases ◽

Cns Disorders ◽

New Treatment ◽

Pituitary Adrenal Axis

Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called “brain–heart axis”. Recent studies suggest that CNS disorders, including neurodegenerative diseases, stroke, and depression, affect cardiovascular function via various mechanisms, such as hypothalamic–pituitary–adrenal axis augmentation. Although this brain–heart axis has been well studied in humans and mice, the involvement of NT signaling in the axis has not been fully investigated. In the first half of this review, we emphasize the importance of NTs not only in the nervous system, but also in the cardiovascular system from the embryonic stage to the adult state. In the second half, we discuss the involvement of NTs in the pathogenesis of cardiovascular diseases, and then examine whether an alteration in NTs could serve as the mediator between neurological disorders and heart dysfunction. The further investigation we propose herein could contribute to finding direct evidence for the involvement of NTs in the axis and new treatment for cardiovascular diseases.

Download Full-text

Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.789834 ◽

2021 ◽

Vol 13 ◽

Author(s):

Banglian Hu ◽

Shengshun Duan ◽

Ziwei Wang ◽

Xin Li ◽

Yuhang Zhou ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Disorders ◽

Neurological Diseases ◽

Colony Stimulating Factor ◽

Loss Of Function ◽

Axonal Spheroids ◽

The Central Nervous System ◽

Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

Download Full-text

Store-Operated Calcium Channels in Physiological and Pathological States of the Nervous System

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2020.600758 ◽

2020 ◽

Vol 14 ◽

Author(s):

Isis Zhang ◽

Huijuan Hu

Keyword(s):

Nervous System ◽

Calcium Channels ◽

Neurological Disorders ◽

Neurological Diseases ◽

Physiological Role ◽

The Body ◽

Store Operated Calcium Entry ◽

Important Pathway ◽

Molecular Components

Store-operated calcium channels (SOCs) are widely expressed in excitatory and non-excitatory cells where they mediate significant store-operated calcium entry (SOCE), an important pathway for calcium signaling throughout the body. While the activity of SOCs has been well studied in non-excitable cells, attention has turned to their role in neurons and glia in recent years. In particular, the role of SOCs in the nervous system has been extensively investigated, with links to their dysregulation found in a wide variety of neurological diseases from Alzheimer’s disease (AD) to pain. In this review, we provide an overview of their molecular components, expression, and physiological role in the nervous system and describe how the dysregulation of those roles could potentially lead to various neurological disorders. Although further studies are still needed to understand how SOCs are activated under physiological conditions and how they are linked to pathological states, growing evidence indicates that SOCs are important players in neurological disorders and could be potential new targets for therapies. While the role of SOCE in the nervous system continues to be multifaceted and controversial, the study of SOCs provides a potentially fruitful avenue into better understanding the nervous system and its pathologies.

Download Full-text

Diabetic db/db mice exhibit central nervous system and peripheral molecular alterations as seen in neurological disorders

Translational Psychiatry ◽

10.1038/tp.2013.42 ◽

2013 ◽

Vol 3 (5) ◽

pp. e263-e263 ◽

Cited By ~ 31

Author(s):

A Ernst ◽

A N Sharma ◽

K M Elased ◽

P C Guest ◽

H Rahmoune ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Disorders ◽

Molecular Alterations

Download Full-text

Multimodality MRI Findings in Patients with End-Stage Renal Disease

BioMed Research International ◽

10.1155/2015/697402 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Hui Juan Chen ◽

Long Jiang Zhang ◽

Guang Ming Lu

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Renal Disease ◽

End Stage Renal Disease ◽

Neurological Disorders ◽

Neurological Complications ◽

Mri Findings ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Patients with end-stage renal disease (ESRD) suffer from a number of complex neurological complications including vascular damage and cognitive dysfunction. It is of great significance to detect the neurological complications and improve the prognosis of ESRD patients. Many new noninvasive MRI techniques have been steadily used for the diagnosis of occult central nervous system complications in ESRD patients. This gives an opportunity to understand the pathophysiological mechanisms of these neurological disorders. This paper is a review that presents the MRI findings of occult brain damage in ESRD patients, outlines the applications of advanced MRI techniques, and introduces a brief perspective in this study field.

Download Full-text

MicroRNA Signatures in Neurological Disorders

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100009902 ◽

2010 ◽

Vol 37 (2) ◽

pp. 177-185 ◽

Cited By ~ 30

Author(s):

Gowhar Shafi ◽

Nishat Aliya ◽

Anjana Munshi

Keyword(s):

Cell Death ◽

Nervous System ◽

Gene Regulation ◽

Neurological Disorders ◽

Mirna Biogenesis ◽

Neuronal Function ◽

Mrna Targets ◽

Transcriptional Gene Regulation ◽

Therapeutic Tools ◽

Intense Research

A class of small, non-coding transcripts called microRNAs (miRNAs) that play a major role in post-transcriptional gene regulation has recently emerged and become the focus of intense research. MicroRNAs are abundant in the nervous system, where they have key roles in development and are likely to be important mediators of plasticity. A highly conserved pathway of miRNA biogenesis is closely linked to the transport and translatability of mRNAs in neurons. MicroRNAs have been shown to modulate programmed cell death during development. Although there are nearly 750 known human miRNA sequences, each of only approximately 20-25 nucleotides in length that bind to multiple mRNA targets, the accurate prediction of miRNA targets seems to lie just beyond our grasp. Nevertheless, the identification of such targets promises to provide new insights into many facets of neuronal function. In this review, we briefly describe miRNA biogenesis and the principle approaches for studying the function of miRNAs and potential application of miRNAs as biomarkers, diagnostic targets, and potential therapeutic tools of human diseases in general and neurological disorders in particular.

Download Full-text

Amino Acids in the Treatment of Neurological Disorders

10.1093/med/9780190497996.003.0035 ◽

2016 ◽

Author(s):

Adam L. Hartman

Keyword(s):

Amino Acids ◽

Nervous System ◽

Neurological Disorders ◽

Mechanisms Of Action ◽

Membrane Transporters ◽

Carbohydrate Restriction ◽

Neuroprotective Effects ◽

Fat Supplementation ◽

Pathway Activity ◽

Dietary Component

Studies of metabolism- and diet-based therapies in epilepsy and neuroprotection have focused primarily on the quality and quantity of fat supplementation or carbohydrate restriction. However, protein is another key dietary component that has not been as thoroughly studied. A number of amino acids have been shown to stop, terminate, or prevent seizures. In addition, some have been shown to exert neuroprotective effects in other neurological disorders. Amino acids (and their metabolites) may exert their effects by acting at membrane or cytoplasmic receptors, serving as substrates for membrane transporters and as modulators of signaling pathway activity. This chapter highlights examples of each of these mechanisms of action in select nervous system disorders.

Download Full-text