scholarly journals Developmental Neurotoxicity: Some Old and New Issues

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Gennaro Giordano ◽  
Lucio G. Costa

The developing central nervous system is often more vulnerable to injury than the adult one. Of the almost 200 chemicals known to be neurotoxic, many are developmental neurotoxicants. Exposure to these compounds in utero or during childhood can contribute to a variety of neurodevelopmental and neurological disorders. Two established developmental neurotoxicants, methylmercury and lead, and two classes of chemicals, the polybrominated diphenyl ether flame retardants and the organophosphorus insecticides, which are emerging as potential developmental neurotoxicants, are discussed in this paper. Developmental neurotoxicants may also cause silent damage, which would manifest itself only as the individual ages, and may contribute to neurodegenerative diseases such as Parkinson’s or Alzheimer’s diseases. Guidelines for developmental neurotoxicity testing have been implemented, but there is still room for their improvement and for searching and validating alternative testing approaches.

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Juárez-Rebollar ◽  
Camilo Rios ◽  
Concepción Nava-Ruíz ◽  
Marisela Méndez-Armenta

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Arash Abdolmaleki ◽  
Sevin Ferdowsi ◽  
Asadollah Asadi ◽  
Yassin Panahi

Context: Neurodegenerative diseases (NDs) are neurological disorders characterized by the degeneration of the central nervous system (CNS). Studies have examined interactions between long non-coding RNAs (lncRNAs) and functioning of the CNS in NDs. In this study, we summarized the role of different lncRNAs in most NDs. Methods: In this study, different papers published between years 2003 and 2020 were reviewed. Results: LncRNAs can play a significant role in the development of brain disorders. Conclusions: The dysregulation of lncRNAs has been shown to affect NDs such as Alzheimer's disease (AD) and Parkinson’s diseases (PD). In this review, we compiled recent findings related to the main lncRNAs associated with brain disorders.


2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ana De Malet ◽  
Sheila Ingerto ◽  
Israel Gañán

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.


2001 ◽  
Vol 75 (17) ◽  
pp. 8268-8282 ◽  
Author(s):  
Seng-Thuon Khuth ◽  
Hideo Akaoka ◽  
Axel Pagenstecher ◽  
Olivier Verlaeten ◽  
Marie-Françoise Belin ◽  
...  

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.


Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1730
Author(s):  
Masashi Fujitani ◽  
Yoshinori Otani ◽  
Hisao Miyajima

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.


2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yang Tian ◽  
Chen Fu ◽  
Yifan Wu ◽  
Yao Lu ◽  
Xuemei Liu ◽  
...  

Exosomes are a type of extracellular vesicles secreted by almost all kinds of mammalian cells that shuttle “cargo” from one cell to another, indicative of its role in cell-to-cell transportation. Interestingly, exosomes are known to undergo alterations or serve as a pathway in multiple diseases, including neurodegenerative diseases. In the central nervous system (CNS), exosomes originating from neurons or glia cells contribute to or inhibit the progression of CNS-related diseases in special ways. In lieu of this, the current study investigated the effect of CNS cell-derived exosomes on different neurodegenerative diseases.


1959 ◽  
Vol 36 (3) ◽  
pp. 501-511
Author(s):  
M. J. WELLS

1. Octopuses blinded by section of the optic nerves were trained by means of 5-10 V. a.c. shocks to reject objects that they would otherwise take. 2. With trials at 3, 5, or 20 min. intervals, in which the test object was always presented to the same arm, animals learned within four or five trials, thereafter rejecting the test object whenever it was presented. 3. When, after a succession of such negative responses, the object was presented to another arm on the other side of the octopus, the result depended upon the rate of training before the change. Thus the object was taken in the trial immediately following the arm change in nineteen out of twenty-six sets of tests with trials at 3 or 5 min. intervals, but in only two out of twelve sets with trials at 20 min. intervals; further experiments in which changes were made between arms on the same side produced similar results. 4. These results are interpreted as showing that changes occurring as a result of experience directly affecting one arm take a period of several hours to spread and become effective in determining the reactions of the rest. This in turn implies the existence of functionally independent neurone fields representing the individual arms, and is discussed in relation to what is already known about the organization of the tactile system of the octopus.


1949 ◽  
Vol 95 (401) ◽  
pp. 826-841 ◽  
Author(s):  
R. K. Freudenberg ◽  
J. P. S. Robertson

This investigation is not concerned with the clinical indications or results of prefrontal leucotomy, but attempts to re-examine changes following the operation, especially in regard to the impairment of some of the manifestations of the highest integrative psychophysiological functions of the central nervous system that may bring about such alterations. Amongst these we were primarily interested in cognitive changes, but the interpretation of apparent cognitive changes led to the consideration of orectic alterations as well. Such changes have so far been impossible to localize exactly, but are considered to be partly related to the phylogenetically more recent parts of the cerebral cortex. Masserman (1946) compared the mechanism of shock treatment and leucotomy with the effects of alcohol and states that “its main actions are those of a cortical depressant,” as manifested by impairment of finer perceptions and discriminations and a “constriction of the integrative field.” He believes that shock therapies and leucotomy partly produce their results by temporary or permanent decorticating effects, “rendering the individual no longer capable of fine spun fantasies or elaborate delusions.” These decorticating effects can be assumed to be reflected in cognitive, conative and emotional alterations following the operation. The interpretation of change following leucotomy presents many difficulties, one of them being that only dysfunction can be related to structural damage of the frontal lobe and not function. Another is that psychotics or severe neurotics operated upon usually do not have a sufficiently intact pre-operative personality to draw conclusions about the normal functions.


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