Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease

2007 ◽  
Vol 87 (3) ◽  
pp. 799-823 ◽  
Author(s):  
Mark F. Mehler ◽  
John S. Mattick
Keyword(s):  
Nervous System ◽  
Rna Editing ◽  
Neurological Diseases ◽  
Cell Types ◽  
State Transitions ◽  
Long Term Memory ◽  
Protein Coding ◽  
Continuous State ◽  
Wide Range

The progressive maturation and functional plasticity of the nervous system in health and disease involve a dynamic interplay between the transcriptome and the environment. There is a growing awareness that the previously unexplored molecular and functional interface mediating these complex gene-environmental interactions, particularly in brain, may encompass a sophisticated RNA regulatory network involving the twin processes of RNA editing and multifaceted actions of numerous subclasses of non-protein-coding RNAs. The mature nervous system encompasses a wide range of cell types and interconnections. Long-term changes in the strength of synaptic connections are thought to underlie memory retrieval, formation, stabilization, and effector functions. The evolving nervous system involves numerous developmental transitions, such as neurulation, neural tube patterning, neural stem cell expansion and maintenance, lineage elaboration, differentiation, axonal path finding, and synaptogenesis. Although the molecular bases for these processes are largely unknown, RNA-based epigenetic mechanisms appear to be essential for orchestrating these precise and versatile biological phenomena and in defining the etiology of a spectrum of neurological diseases. The concerted modulation of RNA editing and the selective expression of non-protein-coding RNAs during seminal as well as continuous state transitions may comprise the plastic molecular code needed to couple the intrinsic malleability of neural network connections to evolving environmental influences to establish diverse forms of short- and long-term memory, context-specific behavioral responses, and sophisticated cognitive capacities.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

Abstract Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

Epilepsy and Stroke Emerging From Climate Change-Related Neurotoxicity

2019 ◽  
pp. 322-347
Author(s):  
Hind Benammi ◽  
Omar El Hiba ◽  
Abdelmohcine Aimrane ◽  
Nadia Zouhairi ◽  
Hicham Chatoui ◽  
...  
Keyword(s):  
Climate Change ◽  
Heavy Metals ◽  
Nervous System ◽  
Toxic Elements ◽  
Neurological Diseases ◽  
Quality Of Water ◽  
Wide Range ◽  
The Impact ◽  
Shed Light

Climate change has an important impact on the environment. As it degrades the quality of water, soil, and area, it also spreads the distribution of many toxic elements, specifically heavy metals and pesticides. The impact of climate change on contamination with heavy metals and pesticides has been well investigated and discussed. The influence of these elements on human health is obviously exacerbated following their extended distribution. Moreover, a wide range of health problems have been associated to such intoxication, among which impairment and dysfunction of the nervous system are prominent. In this chapter, the authors will shed light on two most common neurological diseases such as epilepsy and stroke affecting people worldwide arising from food and water contaminations, mainly with heavy metals and pesticides.

Functional morphology of the platyhelminth nervous system

Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S47-S72 ◽  
Author(s):  
D. W. Halton ◽  
M. K. S. Gustafsson
Keyword(s):  
Nervous System ◽  
Sense Organ ◽  
Neuronal Cell ◽  
Cell Types ◽  
Target Cells ◽  
Life Styles ◽  
Wide Range ◽  
Paracrine Secretion ◽  
Nervous System Evolution ◽  
Neuronal Vesicles

SUMMARYAs the most primitive metazoan phylum, the Platyhelminthes occupies a unique position in nervous system evolution. Centrally, their nervous system consists of an archaic brain from which emanate one or more pairs of longitudinal nerve cords connected by commissures; peripherally, a diverse arrangement of nerve plexuses of varying complexity innervate the subsurface epithelial and muscle layers, and in the parasitic taxa they are most prominent in the musculature of the attachment organs and egg-forming apparatus. There is a range of neuronal-cell types, the majority being multi- and bipolar. The flatworm neuron is highly secretory and contains a heterogeneity of vesicular inclusions, dominated by densecored vesicles, whose contents may be released synaptically or by paracrine secretion for presumed delivery to target cells via the extracellular matrix. A wide range of sense organ types is present in flatworms, irrespective of life-styles. The repertoire of neuronal substances identified cytochemically includes all of the major candidate transmitters known in vertebrates. Two groups of native flatworm neuropeptides have been sequenced, neuropeptide F and FMRFamide-related peptides (FaRPs), and immunoreactivities for these have been localised in dense-cored neuronal vesicles in representatives of all major fiatworm groups. There is evidence of co-localisation of peptidergic and cholinergic elements; serotoninergic components generally occupy a separate set of neurons. The actions of neuronal substances in flatworms are largely undetermined, but FaRPs and 5-HT are known to be myoactive in all of the major groups, and there is immuno-cytochemical evidence that they have a role in the mechanism of egg assembly.

scholarly journals An expanded mouse testis transcriptome and mass spectrometry defines novel proteins

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Jaya Gamble ◽  
Joel Chick ◽  
Kelly Seltzer ◽  
Joel H Graber ◽  
Steven Gygi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Types ◽  
Round Spermatid ◽  
Novel Genes ◽  
Protein Coding ◽  
Novel Proteins ◽  
Wide Range ◽  
Novel Transcripts ◽  
Coding Potential ◽  
Novel Isoforms

The testis transcriptome is exceptionally complex. Despite its complexity, previous testis transcriptome analyses relied on a reductive method for transcript identification, thus underestimating transcriptome complexity. We describe here a more complete testis transcriptome generated by combining Tuxedo, a reductive method, and spliced-RUM, a combinatorial transcript-building approach. Forty-two percent of the expanded testis transcriptome is composed of unannotated RNAs with novel isoforms of known genes and novel genes constituting 78 and 9.8% of the newly discovered transcripts, respectively. Across tissues, novel transcripts were predominantly expressed in the testis with the exception of novel isoforms which were also highly expressed in the adult ovary. Within the testis, novel isoform expression was distributed equally across all cell types while novel genes were predominantly expressed in meiotic and post-meiotic germ cells. The majority of novel isoforms retained their protein-coding potential while most novel genes had low protein-coding potential. However, a subset of novel genes had protein-coding potentials equivalent to known protein-coding genes. Shotgun mass spectrometry of round spermatid total protein identified unique peptides from four novel genes along with seven annotated non-coding RNAs. These analyses demonstrate the testis expresses a wide range of novel transcripts that give rise to novel proteins.

scholarly journals The Bacterial Enzyme RfxCas13d Is Less Neurotoxic Than PspCas13b and Could Be a Promising RNA Editing and Interference Tool in the Nervous System

2021 ◽  
Vol 11 (8) ◽  
pp. 1054
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer
Keyword(s):  
Nervous System ◽  
Purkinje Cells ◽  
Rna Editing ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Significant Inhibition ◽  
Great Promise ◽  
Bacterial Enzymes ◽  
Dendritic Development ◽  
Cerebellar Purkinje Cells

RNA therapies using RNA editing and interference are currently being developed for neurological diseases. The CRISPR-Cas13 system, based on bacterial enzymes, holds great promise for developing efficient tools for RNA therapies. However, neurotoxic activity has been reported for Cas13a, and recent studies have reported toxic effects of PspCas13b and RfxCas13d during zebrafish and Drosophila embryonic development. It is important to investigate the safety of these bacterial enzymes in the context of the nervous system and neuronal development. In this study, we used mouse cerebellar Purkinje cells as a complex neuron type to test for the potential neurotoxic actions of RfxCas13d and PspCas13b. We found that PspCas13b significantly impeded the dendritic development of cultured Purkinje cells, similar to the neurotoxic action of Cas13a. In contrast, RfxCas13d did not exhibit a significant inhibition of dendritic development. A similar trend was found for axonal outgrowth. These results suggest varying neurotoxic properties for different Cas13 ortholog enzymes. We call for more studies to investigate, and possibly mitigate, the neurotoxicity of Cas13 proteins in order to improve the safety of the CRISPR-Cas13 system for RNA therapies.

scholarly journals Graphene-Based Electrode Materials for Neural Activity Detection

Materials ◽  
2021 ◽  
Vol 14 (20) ◽  
pp. 6170
Author(s):  
Weichen Wei ◽  
Xuejiao Wang
Keyword(s):  
Neural Activity ◽  
High Performance ◽  
Electrode Materials ◽  
Neurological Diseases ◽  
Activity Detection ◽  
Neural Signals ◽  
Neural Electrode ◽  
Neural Electrodes ◽  
Wide Range

The neural electrode technique is a powerful tool for monitoring and regulating neural activity, which has a wide range of applications in basic neuroscience and the treatment of neurological diseases. Constructing a high-performance electrode–nerve interface is required for the long-term stable detection of neural signals by electrodes. However, conventional neural electrodes are mainly fabricated from rigid materials that do not match the mechanical properties of soft neural tissues, thus limiting the high-quality recording of neuroelectric signals. Meanwhile, graphene-based nanomaterials can form stable electrode–nerve interfaces due to their high conductivity, excellent flexibility, and biocompatibility. In this literature review, we describe various graphene-based electrodes and their potential application in neural activity detection. We also discuss the biological safety of graphene neural electrodes, related challenges, and their prospects.

scholarly journals Modern aspects of neuropathogenesis and neurological manifestations of COVID-19

2021 ◽  
Vol 17 (2) ◽  
pp. 6-15
Author(s):  
L.A. Dziak ◽  
O.S. Tsurkalenko ◽  
K.V. Chekha ◽  
V.M. Suk
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
The Body ◽  
Altered Level ◽  
Wide Range ◽  
The Central Nervous System ◽  
The Brain

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.

The Integrated Stress Response in Memory and Cognitive Disorders

2020 ◽  
Author(s):  
Jacqunae L. Mays ◽  
Mauro Costa-Mattioli
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Cognitive Disorders ◽  
Memory Formation ◽  
Model Systems ◽  
Long Term Memory ◽  
Integrated Stress Response ◽  
Term Memory ◽  
Wide Range

The integrated stress response (ISR) is an evolutionarily conserved intracellular signaling network that responds to proteostasis defects and stress conditions by tuning protein synthesis rates. While it has been long recognized that long-term memory formation requires new protein synthesis, our understanding of the central translational control mechanisms that regulate memory formation has advanced vastly. Indeed, novel causal and convergent evidence across different species and model systems shows that the ISR serves as a universal regulator of long-term memory formation. This chapter discusses the evidence explaining how inhibition of the ISR enhances long-term memory formation while activation of the ISR prevents it. In addition, it highlights the role of the ISR in different forms of long-lasting synaptic plasticity in the brain. Finally, the chapter addresses how dysregulated ISR signaling contributes to the pathogenesis of a wide range of cognitive and neurodegenerative disorders and discusses the future prospects for therapeutically targeting the ISR for the treatment of cognitive disorders.

Fractionating Executive Functions of Adults With ADHD

2014 ◽  
Vol 21 (11) ◽  
pp. 944-955 ◽  
Author(s):  
Viviane Freire Bueno ◽  
Maria Aparecida da Silva ◽  
Tânia Maria Alves ◽  
Mario Rodrigues Louzã ◽  
Sabine Pompéia
Keyword(s):  
Executive Functions ◽  
Adult Adhd ◽  
Anxiety And Depression ◽  
Control Group ◽  
Long Term Memory ◽  
Depression Symptoms ◽  
Term Memory ◽  
Wide Range ◽  
Healthy Control

Objective: To evaluate the performance of adults with ADHD considering the fractionation of executive functions into six different domains. Method: Participants were adult ADHD patients who were not under the acute effects of medication ( n = 48). Their performance was compared with that of a healthy control group ( n = 20) of comparable age, education, and nonverbal intelligence quotient. The cognitive domains assessed were executive shifting, updating, inhibition of prepotent responses, dual-task performance, planning, and access to long-term memory. We also assessed the symptoms of inattention, hyperactivity/impulsivity, anxiety, and depression by validated questionnaires. Results: Compared with controls, patients reported more symptoms related to ADHD, anxiety and depression symptoms and were impaired in the shifting cost measure and phonemic fluency (measure of access to long-term memory). Conclusion: ADHD in adults selectively impaired executive shifting and access to long-term memory, domains that may alter performance in a wide range of daily tasks.

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