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Ways to Model Neurologic Disorders: New Insights

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 9812

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Special Issue Editors

Dr. Claudia Compagnucci

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Guest Editor

Unit of Molecular Genetics and Functional Genomics, Research Area of Genetics and Rare Diseases, Ospedale Pediatrico Bambino Gesù Viale di San Paolo, 15 00146 Rome, Italy
Interests: induced pluripotent stem cell; rare diseases; cell banking; cellular phenotyping assays; neurogenesis; neurodegeneration

Dr. Emanuela Piermarini

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Guest Editor

Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 W Queen Lane 19129 Philadelphia, United States
Interests: Animal models; Behavior Assays; Cytoskeleton; Neurodegeneration; Signalling; Oxidative Stress

Special Issue Information

Dear Colleagues,

Animal models play a fundamental role for understanding the pathogenesis of several human disorders, but not all diseases can be reproduced in animals. For this reason, the development of the induced pluripotent stem cell (iPSC) technology has become relevant for modelling human disorders. Since 2007, many diseases have been modelled by using iPSCs and, most recently, organoids, i.e., three-dimensional multicellular structures arising from iPSCs, which offer the unique opportunity to investigate and understand the complex 3D cellular phenotype of numerous human pathologies. Modelling human disorders is important as it both improves our comprehension of disease pathogenesis and offers the opportunity to test mechanistically constructed therapeutics which may effectively treat and/or prevent neurological disorders.

This Special Issue will focus on recent advances in the generation of human disease models, with particular emphasis on models of neurologic disorders. Articles offering innovative insights into the multifaceted pathophysiology of neurological diseases are welcome. Original research articles and reviews are invited on all aspects of neurological disease modelling, from animal models to models based on human iPSCs and 3D organoids that better represent the in vivo environment.

Dr. Claudia Compagnucci
Dr. Emanuela Piermarini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

disease modelling
neurogenesis
neurodegeneration
pathogenesis
induced pluripotent stem cell
organoids
cellular phenotyping assays
animal models
molecular mechanisms
pharmacologic treatments

Published Papers (3 papers)

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Research

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21 pages, 2807 KiB

Open AccessArticle

Neonatal Rat Glia Cultured in Physiological Normoxia for Modeling Neuropathological Conditions In Vitro

by Justyna Gargas, Justyna Janowska, Karolina Ziabska, Malgorzata Ziemka-Nalecz and Joanna Sypecka

Int. J. Mol. Sci. 2022, 23(11), 6000; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116000 - 26 May 2022

Cited by 2 | Viewed by 1684

Abstract

Cell culture conditions were proven to highly affect crucial biological processes like proliferation, differentiation, intercellular crosstalk, and senescence. Oxygen tension is one of the major factors influencing cell metabolism and thus, modulating cellular response to pathophysiological conditions. In this context, the presented study aimed at the development of a protocol for efficient culture of rat neonatal glial cells (microglia, astrocytes, and oligodendrocytes) in oxygen concentrations relevant to the nervous tissue. The protocol allows for obtaining three major cell populations, which play crucial roles in sustaining tissue homeostasis and are known to be activated in response to a wide spectrum of external stimuli. The cells are cultured in media without supplement addition to avoid potential modulation of cell processes. The application of active biomolecules for coating culturing surfaces might be useful for mirroring physiological cell interactions with extracellular matrix components. The cell fractions can be assembled as cocultures to further evaluate investigated mechanisms, intercellular crosstalk, or cell response to tested pharmacological compounds. Applying additional procedures, like transient oxygen and glucose deprivation, allows to mimic in vitro the selected pathophysiological conditions. The presented culture system for neonatal rat glial cells is a highly useful tool for in vitro modeling selected neuropathological conditions. Full article

(This article belongs to the Special Issue Ways to Model Neurologic Disorders: New Insights)

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19 pages, 4774 KiB

Open AccessArticle

Cerebral Organoids for Modeling of HSV-1-Induced-Amyloid β Associated Neuropathology and Phenotypic Rescue

by Haowen Qiao, Wen Zhao, Moujian Guo, Lili Zhu, Tao Chen, Jibo Wang, Xiaodong Xu, Zhentao Zhang, Ying Wu and Pu Chen

Int. J. Mol. Sci. 2022, 23(11), 5981; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23115981 - 26 May 2022

Cited by 7 | Viewed by 2717

Abstract

Herpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the Amyloid β (Aβ) associated neuropathology. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians’ brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced Aβ associated neuropathology and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infected cerebral organoids recapitulated Aβ associated neuropathology including the multicellular Aβ deposition, dysregulated endogenous AD mediators, reactive gliosis, neuroinflammation, and neural loss, indicating that cerebral organoids offer an opportunity for modeling the interaction of HSV-1 with the complex phenotypes across the genetic, cellular, and tissue levels of the human Alzheimer’s disease (AD). Furthermore, we identified that two antiviral drugs, namely Ribavirin (RBV) and Valacyclovir (VCV), inhibited HSV-1 replication and rescued the neuropathological phenotypes associated with AD in the HSV-1-infected cerebral organoids, implying their therapeutic potential to slow down the progression of AD. Our study provides a high-fidelity human-relevant in-vitro HSV-1 infection model to reconstitute the multiscale neuropathological features associated with AD and discover therapeutic drug candidates relevant to the AD viral hypothesis. Full article

(This article belongs to the Special Issue Ways to Model Neurologic Disorders: New Insights)

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Review

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29 pages, 5157 KiB

Open AccessReview

Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies

by Angela Lanciotti, Maria Stefania Brignone, Pompeo Macioce, Sergio Visentin and Elena Ambrosini

Int. J. Mol. Sci. 2022, 23(1), 274; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010274 - 27 Dec 2021

Cited by 5 | Viewed by 4785

Abstract

Astrocytes are very versatile cells, endowed with multitasking capacities to ensure brain homeostasis maintenance from brain development to adult life. It has become increasingly evident that astrocytes play a central role in many central nervous system pathologies, not only as regulators of defensive responses against brain insults but also as primary culprits of the disease onset and progression. This is particularly evident in some rare leukodystrophies (LDs) where white matter/myelin deterioration is due to primary astrocyte dysfunctions. Understanding the molecular defects causing these LDs may help clarify astrocyte contribution to myelin formation/maintenance and favor the identification of possible therapeutic targets for LDs and other CNS demyelinating diseases. To date, the pathogenic mechanisms of these LDs are poorly known due to the rarity of the pathological tissue and the failure of the animal models to fully recapitulate the human diseases. Thus, the development of human induced pluripotent stem cells (hiPSC) from patient fibroblasts and their differentiation into astrocytes is a promising approach to overcome these issues. In this review, we discuss the primary role of astrocytes in LD pathogenesis, the experimental models currently available and the advantages, future evolutions, perspectives, and limitations of hiPSC to study pathologies implying astrocyte dysfunctions. Full article

(This article belongs to the Special Issue Ways to Model Neurologic Disorders: New Insights)

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