scholarly journals Modeling Neuronal Diseases in Zebrafish in the Era of CRISPR

2020 ◽  
Vol 18 (2) ◽  
pp. 136-152
Author(s):  
Angeles Edith Espino-Saldaña ◽  
Roberto Rodríguez-Ortiz ◽  
Elizabeth Pereida-Jaramillo ◽  
Ataúlfo Martínez-Torres

Background: Danio rerio is a powerful experimental model for studies in genetics and development. Recently, CRISPR technology has been applied in this species to mimic various human diseases, including those affecting the nervous system. Zebrafish offer multiple experimental advantages: external embryogenesis, rapid development, transparent embryos, short life cycle, and basic neurobiological processes shared with humans. This animal model, together with the CRISPR system, emerging imaging technologies, and novel behavioral approaches, lay the basis for a prominent future in neuropathology and will undoubtedly accelerate our understanding of brain function and its disorders. Objective: Gather relevant findings from studies that have used CRISPR technologies in zebrafish to explore basic neuronal function and model human diseases. Method: We systematically reviewed the most recent literature about CRISPR technology applications for understanding brain function and neurological disorders in D. rerio. We highlighted the key role of CRISPR in driving forward our understanding of particular topics in neuroscience. Results: We show specific advances in neurobiology when the CRISPR system has been applied in zebrafish and describe how CRISPR is accelerating our understanding of brain organization. Conclusion: Today, CRISPR is the preferred method to modify genomes of practically any living organism. Despite the rapid development of CRISPR technologies to generate disease models in zebrafish, more efforts are needed to efficiently combine different disciplines to find the etiology and treatments for many brain diseases.

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 281
Author(s):  
Catherine Baker ◽  
Matthew S. Hayden

The discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has revolutionized gene editing research. Through the repurposing of programmable RNA-guided CRISPR-associated (Cas) nucleases, CRISPR-based genome editing systems allow for the precise modification of specific sites in the human genome and inspire novel approaches for the study and treatment of inherited and acquired human diseases. Here, we review how CRISPR technologies have stimulated key advances in dermatologic research.  We discuss the role of CRISPR in genome editing for cutaneous disease and highlight studies on the use of CRISPR-Cas technologies for genodermatoses, cutaneous viruses and bacteria, and melanoma. Additionally, we examine key limitations of current CRISPR technologies, including the challenges these limitations pose for the widespread therapeutic application of CRISPR-based therapeutics.


2020 ◽  
Vol 4 (1) ◽  
pp. 1-29 ◽  
Author(s):  
Sepideh Sadaghiani ◽  
Jonathan Wirsich

The discovery of a stable, whole-brain functional connectivity organization that is largely independent of external events has drastically extended our view of human brain function. However, this discovery has been primarily based on functional magnetic resonance imaging (fMRI). The role of this whole-brain organization in fast oscillation-based connectivity as measured, for example, by electroencephalography (EEG) and magnetoencephalography (MEG) is only beginning to emerge. Here, we review studies of intrinsic connectivity and its whole-brain organization in EEG, MEG, and intracranial electrophysiology with a particular focus on direct comparisons to connectome studies in fMRI. Synthesizing this literature, we conclude that irrespective of temporal scale over four orders of magnitude, intrinsic neurophysiological connectivity shows spatial similarity to the connectivity organization commonly observed in fMRI. A shared structural connectivity basis and cross-frequency coupling are possible mechanisms contributing to this similarity. Acknowledging that a stable whole-brain organization governs long-range coupling across all timescales of neural processing motivates researchers to take “baseline” intrinsic connectivity into account when investigating brain-behavior associations, and further encourages more widespread exploration of functional connectomics approaches beyond fMRI by using EEG and MEG modalities.


2021 ◽  
Vol 15 ◽  
Author(s):  
Nan Zhang ◽  
Fengling He ◽  
Ting Li ◽  
Jinzhi Chen ◽  
Liping Jiang ◽  
...  

Exosomes are a subset of extracellular vesicles that act as messengers to facilitate communication between cells. Non-coding RNAs, proteins, lipids, and microRNAs are delivered by the exosomes to target molecules (such as proteins, mRNAs, or DNA) of host cells, thereby playing a key role in the maintenance of normal brain function. However, exosomes are also involved in the occurrence, prognosis, and clinical treatment of brain diseases, such as Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury. In this review, we have summarized novel findings that elucidate the role of exosomes in the occurrence, prognosis, and treatment of brain diseases.


2019 ◽  
Vol 2 (1) ◽  
pp. e201900325 ◽  
Author(s):  
Eloise Hudry ◽  
Jacob Klickstein ◽  
Claudia Cannavo ◽  
Rosemary Jackson ◽  
Alona Muzikansky ◽  
...  

Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer’s disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8–10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18–20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE’s role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 281
Author(s):  
Catherine Baker ◽  
Matthew S. Hayden

The discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system has revolutionized gene editing research. Through the repurposing of programmable RNA-guided CRISPR-associated (Cas) nucleases, CRISPR-based genome editing systems allow for the precise modification of specific sites in the human genome and inspire novel approaches for the study and treatment of inherited and acquired human diseases. Here, we review how CRISPR technologies have stimulated key advances in dermatologic research.  We discuss the role of CRISPR in genome editing for cutaneous disease and highlight studies on the use of CRISPR-Cas technologies for genodermatoses, cutaneous viruses and bacteria, and melanoma. Additionally, we examine key limitations of current CRISPR technologies, including the challenges these limitations pose for the widespread therapeutic application of CRISPR-based therapeutics.


Author(s):  
A. Kawaoi

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.


Author(s):  
C. S. Potter ◽  
C. D. Gregory ◽  
H. D. Morris ◽  
Z.-P. Liang ◽  
P. C. Lauterbur

Over the past few years, several laboratories have demonstrated that changes in local neuronal activity associated with human brain function can be detected by magnetic resonance imaging and spectroscopy. Using these methods, the effects of sensory and motor stimulation have been observed and cognitive studies have begun. These new methods promise to make possible even more rapid and extensive studies of brain organization and responses than those now in use, such as positron emission tomography.Human brain studies are enormously complex. Signal changes on the order of a few percent must be detected against the background of the complex 3D anatomy of the human brain. Today, most functional MR experiments are performed using several 2D slice images acquired at each time step or stimulation condition of the experimental protocol. It is generally believed that true 3D experiments must be performed for many cognitive experiments. To provide adequate resolution, this requires that data must be acquired faster and/or more efficiently to support 3D functional analysis.


2020 ◽  
Vol 19 (7) ◽  
pp. 509-526
Author(s):  
Qin Huang ◽  
Fang Yu ◽  
Di Liao ◽  
Jian Xia

: Recent studies implicate microbiota-brain communication as an essential factor for physiology and pathophysiology in brain function and neurodevelopment. One of the pivotal mechanisms about gut to brain communication is through the regulation and interaction of gut microbiota on the host immune system. In this review, we will discuss the role of microbiota-immune systeminteractions in human neurological disorders. The characteristic features in the development of neurological diseases include gut dysbiosis, the disturbed intestinal/Blood-Brain Barrier (BBB) permeability, the activated inflammatory response, and the changed microbial metabolites. Neurological disorders contribute to gut dysbiosis and some relevant metabolites in a top-down way. In turn, the activated immune system induced by the change of gut microbiota may deteriorate the development of neurological diseases through the disturbed gut/BBB barrier in a down-top way. Understanding the characterization and identification of microbiome-immune- brain signaling pathways will help us to yield novel therapeutic strategies by targeting the gut microbiome in neurological disease.


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