The neurological toxicity of heavy metals: A fish perspective Green, Adrian J.; Planchart, Antonio
Comparative biochemistry and physiology. Part C, Toxicology & pharmacology/Comparative biochemistry and physiology. Toxicology & pharmacology,
June 2018, 2018-Jun, 2018-06-00, Volume:
208
Journal Article
Peer reviewed
Open access
The causes of neurodegenerative diseases are complex with likely contributions from genetic susceptibility and environmental exposures over an organism's lifetime. In this review, we examine the role ...that aquatic models, especially zebrafish, have played in the elucidation of mechanisms of heavy metal toxicity and nervous system function over the last decade. Focus is applied to cadmium, lead, and mercury as significant contributors to central nervous system morbidity, and the application of numerous transgenic zebrafish expressing fluorescent reporters in specific neuronal populations or brain regions enabling high-resolution neurodevelopmental and neurotoxicology research.
Uncaria rhynchophylla (Miq.) Jacks (Rubinaceae), a common herbal medicine known as Gou-teng in Chinese, is commonly used in Chinese medicine practice for the treatment of convulsions, hypertension, ...epilepsy, eclampsia and other cerebral diseases. The major active components of U. rhynchophylla are alkaloids, terpenoids and flavonoids. The protective effects of U. rhynchophylla and its major components on central nervous system (CNS) have become a focus of research in recent decades.
The study aimed to systematically summarize the pharmacological activities of U. rhynchophylla and its major components on the CNS.
This review summarized the experimental findings from our laboratories, together with other literature data obtained through a comprehensive search of databases including the Pubmed and the Web of Science.
U. rhynchophylla and its major components such as rhynchophylline and isorhynchophylline have been shown to have neuroprotective effects on Alzheimer's disease, Parkinson's disease, depression, cerebral ischaemia through a number of mechanisms including anti-oxidant, anti-inflammatory actions and regulation on neurotransmitters.
U. rhynchophylla and its major components have multiple beneficial pharmacological effects on CNS. Further studies on U. rhynchophylla and its major components are warranted to fully illustrate the underlying molecular mechanisms, pharmacokinetics, and toxicological profiles of these naturally occurring compounds and their potential for clinical application.
Highlights • Uncontrolled up-regulation of type I interferon signaling can cause human disease. • Human monogenic type I interferonopathies are being increasingly recognized. • Therapies will likely ...become available to control type I interferon up-regulation.
Only relatively recently has it become clear that mammalian genomes encode tens of thousands of long non-coding RNAs (lncRNAs). A striking 40% of these are expressed specifically in the brain, where ...they show precisely regulated temporal and spatial expression patterns. This begs the question, what is the functional role of these many lncRNA transcripts in the brain? Here we canvass a growing number of mechanistic studies that have elucidated central roles for lncRNAs in the regulation of nervous system development and function. We also survey studies indicating that neurological and psychiatric disorders may ensue when these mechanisms break down. Finally, we synthesize these insights with evidence from comparative genomics to argue that lncRNAs may have played important roles in brain evolution, by virtue of their abundant sequence innovation in mammals and plausible mechanistic connections to the adaptive processes that occurred recently in the primate and human lineages.
Thousands of lncRNAs exhibit precise spatiotemporal expression in the nervous system. Briggs et al. canvass emerging studies showing the mechanistic importance of lncRNAs in brain development, function, and disease. They synthesize these functions with comparative genomic evidence to implicate lncRNAs in brain evolution.
Controversies in Neurosurgery II reflects real-world situations where multiple treatment options are often considered for difficult neurosurgical cases. Each chapter begins with an opening case in ...which experts describe the pros and cons of different treatment methodologies and operative techniques, helping neurosurgeons select the best treatment plan for individual patients in their practice. It is informed with the expertise of more than 100 of the worlds preeminent neurosurgeons. Key features: * Experts from all over the world offer their opinions on more than 20 controversial hot topics in neurosurgery, including a discussion about whether transcranial or endoscopic approaches are the better option for resecting colloid cysts and a lively debate about the optimal treatment of giant ophthalmic artery aneurysms * All treatment options are presented concisely in one volume, so that neurosurgeons dont have to spend time consulting other sources * The moderators conclusion at the end of each chapter explains the scientific evidence about the case and synthesizes the views presented Controversies in Neurosurgery II will be treasured by neurosurgeons and neurosurgery residents as well as by neurologists and neuroradiologists and will be a key volume in their medical libraries for years to come.
Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by ...corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis.
To establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)-immunoglobulin ...G (IgG) neuropathy.
Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed.
One hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer 75%) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG. Patients with CRMP5 had painful axonal polyradiculoneuropathy (65%), mostly asymmetric onset (84%), with neuropathy predating cancer diagnosis by 185 days (range 60-540 days). Most cases (79%) had moderate to severe neuropathic pain, all on neuropathic medications (median 2, range 1-4), opioids in 39%. Nerve biopsies (n = 2) showed microvascular inflammation with axonal degeneration. Compared to ANNA1 alone, CRMP5 neuropathy has a higher prevalence of pain (79% vs 46%,
= 0.008), asymmetric polyradiculoneuropathy (54% vs 12%,
< 0.001), and inflammatory spinal fluids (elevated CSF protein or nucleated cell count 92% vs 60%,
= 0.022). Cerebellar ataxia (21%), myelopathy (19%), and optic neuritis and/or retinitis (11%) were common neurologic accompaniments. CRMP5 cases had significant pain reduction by immunotherapy (
< 0.001). Specifically, high-dose corticosteroid administration was associated with improvement/stabilization in neuropathy impairment scores (
= 0.012) (Class IV). Patients with CRMP5 had better 5-year survival than patients with ANNA1 (67% vs 32%,
= 0.012).
Painful axonal asymmetric polyradiculoneuropathy is established as the major CRMP5 autoimmune neuropathy presentation and is distinguishable from other paraneoplastic neuropathies, including by ANNA1 autoimmunity. Patients with this phenotype should be prompted for CRMP5-IgG testing to assist in early cancer diagnosis.
The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ...the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and ...adulthood. The subsets of CNS myeloid cells identified so far, including parenchymal microglia and non-parenchymal meningeal, perivascular and choroid-plexus macrophages, as well as disease-associated monocytes, have classically been distinguished on the basis of their surface epitope expression, localization and morphology. However, studies using cell-specific targeting, in vivo imaging, single-cell expression analysis and other sophisticated tools have now increased the depth of knowledge of this immune-cell compartment and call for reevaluation of the traditional views on the origin, fate and function of distinct CNS myeloid subsets. The concepts of CNS macrophage biology that are emerging from these new insights have broad implications for the understanding and treatment of CNS diseases.
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