Submit to Biology Review for Biology Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Brain Damage and Repair: From Molecular Effects to CNS Disorders

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Neuroscience".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 42336

Share This Special Issue

Special Issue Editors

Dr. Olivier Armant

E-Mail Website
Guest Editor

Laboratoire d’Ecotoxicologie des radionucléides, Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSE-ENV/SRTE/LECO, Bâtiment 183, Cadarache, BP3, 13115 Saint Paul-lez-Durance, France
Interests: ionizing radiation; developmental biology; systems biology; neurogenesis; DNA damages; disease modeling; epigenetics

Dr. Christelle Adam-Guillermin

E-Mail Website
Guest Editor

Laboratoire d’Ecotoxicologie des radionucléides, Institut de Radioprotection et de Sûreté Nucléaire, IRSN/PSE-SANTE/SDOS/LMDN, Cadarache, BP3, 13115 Saint Paul-lez-Durance, France
Interests: genotoxicity; environmental radioactivity; dosimetry; epigenetics; radioactivity; toxicity; ecology; molecular biology; radiation detection; ecotoxicology

Special Issue Information

Dear Colleagues,

Emerging evidence indicates that chronic exposure to environmental stressors can perturb central nervous system (CNS) development, increasing the risk of brain dysfunction after birth. During the last decade, major advances have been made in our understanding of the mechanisms driving the development of a fully functional brain from a limited pool of stem cells. However, further knowledge is required to understand how these processes are altered by environmental stressors, such as viral infection, injury, inflammation, DNA damage, and exposure to pollutants, and therefore be able to predict the etiology of neurological disorders.

We propose in this Special Issue to bridge the gap between molecular and individual effects in order to understand how environmental stressors perturb neurogenesis (in embryos and adults) and translate into cognitive and behavioral phenotypes. Recent epidemiological studies highlight the environment as a potential source of chronic pollutions that can impact heath. In the field of human health, monitoring chronical exposures to toxicants throughout the entire lifespan, including the prenatal lifespan, is formalized in the concept of exposome, and takes advantage of the recent advances in high-throughput technologies including molecular epidemiology, mutiomics, systems biology, and personal medicine. In parallel to these studies in human health, innovative in vitro models are being developed, including cerebral organoids from IP cells as well as complex animal models using CRISPR-Cas, that contribute to our understanding of both the basic processes of brain development and the effects of gene disruptions and exposures to stressors or toxicants on brain functionalities.

The integration of different fields of research is instrumental to our ability to extend our knowledge of the links among the genome, the epigenome, the environment, and phenotypes. Bringing together current research encompassing toxicology, epidemiology, developmental biology, DNA damage, oxidative stress, regeneration, neuro-inflammation, toxico-genomics, and stem cells and stem cell behavior may contribute to providing us with a clearer picture of how environmental factors impact upon brain development. Such an overview is likely to both stimulate the emergence of expert opinion on what remains to be discovered and promote the development of innovative diagnostic, prognostic, and therapeutic strategies.

Dr. Olivier Armant
Dr. Christelle Adam-Guillermin
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. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

toxicology
development
epidemiology
central nervous system
oxidative stress
DNA damage
systems biology
stem cells
regeneration

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

2 pages, 183 KiB

Open AccessEditorial

Brain Damage and Repair: From Molecular Effects to Central Nervous System Disorders

by Olivier Armant and Christelle Adam-Guillermin

Biology 2021, 10(6), 489; https://doi.org/10.3390/biology10060489 - 31 May 2021

Viewed by 1656

Abstract

Chronical exposures to biological, chemical and physical stressors can be particularly detrimental during the early phase of embryonic development, increasing the risk of brain dysfunctions after birth [...] Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

Research

Jump to: Editorial, Review

15 pages, 1717 KiB

Open AccessArticle

Targeted Dorsal Dentate Gyrus or Whole Brain Irradiation in Juvenile Mice Differently Affects Spatial Memory and Adult Hippocampal Neurogenesis

by Céline Serrano, Morgane Dos Santos, Dimitri Kereselidze, Louison Beugnies, Philippe Lestaevel, Roseline Poirier and Christelle Durand

Biology 2021, 10(3), 192; https://doi.org/10.3390/biology10030192 - 4 Mar 2021

Cited by 6 | Viewed by 2355

Abstract

The cognitive consequences of postnatal brain exposure to ionizing radiation (IR) at low to moderate doses in the adult are not fully established. Because of the advent of pediatric computed tomography scans used for head exploration, improving our knowledge of these effects represents a major scientific challenge. To evaluate how IR may affect the developing brain, models of either whole brain (WB) or targeted dorsal dentate gyrus (DDG) irradiation in C57Bl/6J ten-day-old male mice were previously developed. Here, using these models, we assessed and compared the effect of IR (doses range: 0.25–2 Gy) on long-term spatial memory in adulthood using a spatial water maze task. We then evaluated the effects of IR exposure on adult hippocampal neurogenesis, a form of plasticity involved in spatial memory. Three months after WB exposure, none of the doses resulted in spatial memory impairment. In contrast, a deficit in memory retrieval was identified after DDG exposure for the dose of 1 Gy only, highlighting a non-monotonic dose-effect relationship in this model. At this dose, a brain irradiated volume effect was also observed when studying adult hippocampal neurogenesis in the two models. In particular, only DDG exposure caused alteration in cell differentiation. The most deleterious effect observed in adult hippocampal neurogenesis after targeted DDG exposure at 1 Gy may contribute to the memory retrieval deficit in this model. Altogether these results highlight the complexity of IR mechanisms in the brain that can lead or not to cognitive disorders and provide new knowledge of interest for the radiation protection of children. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Figure 1

15 pages, 5083 KiB

Open AccessArticle

Collimated Microbeam Reveals that the Proportion of Non-Damaged Cells in Irradiated Blastoderm Determines the Success of Development in Medaka (Oryzias latipes) Embryos

by Takako Yasuda, Tomoo Funayama, Kento Nagata, Duolin Li, Takuya Endo, Qihui Jia, Michiyo Suzuki, Yuji Ishikawa, Hiroshi Mitani and Shoji Oda

Biology 2020, 9(12), 447; https://doi.org/10.3390/biology9120447 - 5 Dec 2020

Cited by 5 | Viewed by 4495

Abstract

It has been widely accepted that prenatal exposure to ionizing radiation (IR) can affect embryonic and fetal development in mammals, depending on dose and gestational age of the exposure, however, the precise machinery underlying the IR-induced disturbance of embryonic development is still remained elusive. In this study, we examined the effects of gamma-ray irradiation on blastula embryos of medaka and found transient delay of brain development even when they hatched normally with low dose irradiation (2 and 5 Gy). In contrast, irradiation of higher dose of gamma-rays (10 Gy) killed the embryos with malformations before hatching. We then conducted targeted irradiation of blastoderm with a collimated carbon-ion microbeam. When a part (about 4, 10 and 25%) of blastoderm cells were injured by lethal dose (50 Gy) of carbon-ion microbeam irradiation, loss of about 10% or less of blastoderm cells induced only the transient delay of brain development and the embryos hatched normally, whereas embryos with about 25% of their blastoderm cells were irradiated stopped development at neurula stage and died. These findings strongly suggest that the developmental disturbance in the IR irradiated embryos is determined by the proportion of severely injured cells in the blastoderm. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Figure 1

16 pages, 3108 KiB

Open AccessArticle

The Neurotrophic Function of Glucagon-Like Peptide-1 Promotes Human Neuroblastoma Differentiation via the PI3K-AKT Axis

by Jenq-Lin Yang, Yu-Ting Lin, Wei-Yu Chen, Yun-Ru Yang, Shu-Fang Sun and Shang-Der Chen

Biology 2020, 9(11), 348; https://doi.org/10.3390/biology9110348 - 22 Oct 2020

Cited by 14 | Viewed by 3736

Abstract

Background: Neurons are terminally-differentiated cells that generally develop from neuronal stem cells stimulated by various neurotrophic factors such as NGF, BDNF, NT3, and NT-4. Neurotrophic factors have multiple functions for neurons, including enabling neuronal development, growth, and protection. Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that enhances cellular glucose up-take to decrease blood sugar levels. However, many studies suggest that the function of GLP-1 is not limited to the regulation of blood sugar levels. Instead, it may also act as a neurotrophic factor with a role in ensuring neuronal survival and neurite outgrowth, as well as protecting synaptic plasticity and memory formation. Methods: The SH-SY5Y cells were differentiated by sequential treatments of retinoic acid and GLP-1 treatment within polyethylenimine-coated dishes under serum-free Neurobasal medium. PI3K inhibitor (LY294002) and MEK inhibitor (U0126) were used to determine the signaling pathway in regulation of neuronal differentiation. Neuronal marker (TUJ1) and synaptic markers (synapsin 1, synaptophysin, and PSD95) as well as single cell patch-clamp were applied to determine maturity of neurons. Antibodies of AMPA receptor, NMDA receptor subunit 2A, dopamine receptor D1, muscarinic acetylcholine receptor 2, and nicotinic acetylcholine receptor α4 were used to examine the types of differentiated neurons. Results: Our study’s results demonstrated that the treatment with GLP-1 of SH-SY5Y human neuroblastoma cells increased the expression of AMPA receptors, NMDA receptors, dopamine receptors, synaptic proteins-synapsin 1, synaptophysin, and postsynaptic density protein 95, but not muscular and nicotinic acetylcholine receptors. In addition, the biomarker of dividing neuronal cells, vimentin, was decreased after treatment with GLP-1. Tuj1 immunostaining images showed that GLP-1 induced neurite processes and the development of neuronal morphologies. The GLP-1-differentiated neurons were able to be induced to generate action potentials by single cell patch-clamp. Our study also suggested that the PI3K-AKT axis is the dominant signaling pathway promoting the differentiation of SH-SY5Y cells into mature and functional neurons in response to GLP-1 receptor activation. Conclusions: The sequential treatment of retinoic acid and GLP-1 within a serum-free medium is able to trigger the differentiation of SH-SY5Y cells into morphologically and physiologically mature glutamatergic and dopaminergic neurons. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Figure 1

18 pages, 3777 KiB

Open AccessArticle

Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility

by Michiyo Suzuki, Zu Soh, Hiroki Yamashita, Toshio Tsuji and Tomoo Funayama

Biology 2020, 9(9), 289; https://doi.org/10.3390/biology9090289 - 14 Sep 2020

Cited by 7 | Viewed by 6461

Abstract

To clarify the tissue responsible for a biological function, that function can be experimentally perturbed by an external stimulus, such as radiation. Radiation can be precisely and finely administered and any subsequent change in function examined. To investigate the involvement of the central nervous system (CNS) in Caenorhabditis elegans’ locomotion, we irradiated a limited 20-µm-diameter area of the CNS with a single dose and evaluated the resulting effects on motility. However, whether irradiated area (beam size)-dependent or dose-dependent effects on motility occur via targeted irradiation remain unknown. In the present study, we examined the irradiated area- and dose-dependent effects of CNS-targeted irradiation on the motility of C. elegans using a collimating microbeam system and confirmed the involvement of the CNS and body-wall muscle cells around the CNS in motility. After CNS-targeted microbeam irradiation, C. elegans’ motility was assayed. The results demonstrated a dose-dependent effect of CNS-targeted irradiation on motility reflecting direct effects on the irradiated CNS. In addition, when irradiated with 1000-Gy irradiation, irradiated area (beam size)-dependent effects were observed. This method has two technical advantages: Performing a series of on-chip imaging analyses before and after irradiation and targeted irradiation using a distinct ion-beam size. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Figure 1

18 pages, 1750 KiB

Open AccessArticle

Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis

by Jennifer Mayordomo-Cava, Guillermo Iborra-Lázaro, Souhail Djebari, Sara Temprano-Carazo, Irene Sánchez-Rodríguez, Danko Jeremic, Agnès Gruart, José María Delgado-García, Lydia Jiménez-Díaz and Juan D. Navarro-López

Biology 2020, 9(7), 175; https://doi.org/10.3390/biology9070175 - 20 Jul 2020

Cited by 15 | Viewed by 4908

Abstract

In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-β (Aβ) peptides have been shown to play a causal role. Among different Aβ species, Aβ_25–35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble Aβ forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of Aβ_25–35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. Aβ_25–35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in Aβ_25–35 amyloidosis model. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

21 pages, 2028 KiB

Open AccessReview

Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

by Swapnil Gupta, Panpan You, Tanima SenGupta, Hilde Nilsen and Kulbhushan Sharma

Biology 2021, 10(2), 163; https://doi.org/10.3390/biology10020163 - 19 Feb 2021

Cited by 16 | Viewed by 5932

Abstract

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Graphical abstract

11 pages, 657 KiB

Open AccessReview

Toward a Better Testing Paradigm for Developmental Neurotoxicity: OECD Efforts and Regulatory Considerations

by Magdalini Sachana, Timothy J. Shafer and Andrea Terron

Biology 2021, 10(2), 86; https://doi.org/10.3390/biology10020086 - 23 Jan 2021

Cited by 45 | Viewed by 4434

Abstract

Characterization of potential chemical-induced developmental neurotoxicity (DNT) hazard is considered for risk assessment purposes by many regulatory sectors. However, due to test complexity, difficulty in interpreting results and need of substantial resources, the use of the in vivo DNT test guidelines has been limited and animal data on DNT are scarce. To address challenging endpoints such as DNT, the Organisation for Economic Co-Operation and Development (OECD) chemical safety program has been working lately toward the development of integrated approaches for testing and assessment (IATA) that rely on a combination of multiple layers of data (e.g., in vitro, in silico and non-mammalian in vivo models) that are supported by mechanistic knowledge organized according to the adverse outcome pathway (AOP) framework. In 2017, the OECD convened a dedicated OECD expert group to develop a guidance document on the application and interpretation of data derived from a DNT testing battery that relies on key neurodevelopmental processes and is complemented by zebrafish assays. This review will provide a brief overview of the OECD DNT project and summarize various achievements of relevance to the project. The review also presents an opportunity to describe considerations for uptake of the DNT in an in vitro battery in a regulatory context. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Figure 1

15 pages, 1973 KiB

Open AccessReview

Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery

by Orsolya M. Tóth, Ákos Menyhárt, Rita Frank, Dóra Hantosi, Eszter Farkas and Ferenc Bari

Biology 2020, 9(12), 460; https://doi.org/10.3390/biology9120460 - 11 Dec 2020

Cited by 53 | Viewed by 6643

Abstract

Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be harnessed for the targeted delivery of neuroprotective agents. Ischemic tissue acidosis, which represents the accumulation of lactic acid in malperfused brain tissue is significantly exacerbated by the recurrence of spreading depolarizations. Deepening acidosis itself activates specific ion channels to cause neurotoxic cellular Ca²⁺ accumulation and cytotoxic edema. These processes are thought to contribute to the loss of the ischemic penumbra. The unique metabolic status of the ischemic penumbra has been exploited to identify the penumbra zone with imaging tools. Importantly, acidosis in the ischemic penumbra may also be used to guide therapeutic intervention. Agents with neuroprotective promise are suggested here to be delivered selectively to the ischemic penumbra with pH-responsive smart nanosystems. The administered nanoparticels release their cargo in acidic tissue environment, which reliably delineates sites at risk of injury. Therefore, tissue pH-targeted drug delivery is expected to enrich sites of ongoing injury with the therapeutical agent, without the risk of unfavorable off-target effects. Full article

(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)

► Show Figures

Journal Menu

Journal Browser

Brain Damage and Repair: From Molecular Effects to CNS Disorders

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI