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Molecular Research on Neural Stem Cells in Physiological and Pathological Condition

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

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 12616

Special Issue Editors

Dr. Daniele Bottai

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, Section of Pharmacology and Biosciences, University or Milan Assistant, Via Balzaretti 9, 20133 Milan, Italy
Interests: neural stem cells; glycosphingolipids; neurological diseases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ola Hermanson

E-Mail Website
Guest Editor
Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden
Interests: stem cell; nervous system; cancer cell biology

Special Issue Information

Dear Colleagues, 

In the late twentieth-century, neural stem cells (NSCs) strongly entered the scientific panorama.

NSC physiology has been thoroughly studied, but the responses of NSCs to environment-specific stimuli remain to be completely elucidated. The effects of external or internal stimuli on NSCs depend on the niche where they reside and might be the result of different factors. Indeed, NSCs respond to hormones produced by the body, to an external environmental condition such as pollution, radiation, food, drugs, physical activity, and microgravity, by the activation of different and alternative pathways. These factors can influence the physiological properties of the NSCs such as proliferation self-maintenance, differentiation, and maturation. Neurological diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, spinal muscle atrophy, amyotrophic lateral sclerosis, and others can be characterized by the different behaviors of NSCs, affecting the fine-tuning of the molecular pathways that need to be depicted in detail for each disease.

For this topic, experts in the field are invited to contribute with research papers and critical reviews on unravelling the molecular mechanisms with which NSCs, in the various niches of the invertebrate and vertebrate brain, respond to their environment in physiological and pathological situations.

Dr. Daniele Bottai
Prof. Dr. Ola Hermanson
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

  • neurogenesis
  • gene expression
  • neurological diseases
  • cell metabolism
  • mitochondria
  • signaling pathway
  • environment effect
  • epigenetic
  • secretome
  • oxidative stress

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Published Papers (4 papers)

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Research

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24 pages, 6892 KiB  
Article
Role of Running-Activated Neural Stem Cells in the Anatomical and Functional Recovery after Traumatic Brain Injury in p21 Knock-Out Mice
by Jonathan Isacco Battistini, Valentina Mastrorilli, Vittoria Nicolis di Robilant, Daniele Saraulli, Sara Marinelli and Stefano Farioli Vecchioli
Int. J. Mol. Sci. 2023, 24(3), 2911; https://doi.org/10.3390/ijms24032911 - 2 Feb 2023
Cited by 8 | Viewed by 2807
Abstract
Traumatic brain injury (TBI) represents one of the most common worldwide causes of death and disability. Clinical and animal model studies have evidenced that TBI is characterized by the loss of both gray and white matter, resulting in brain atrophy and in a [...] Read more.
Traumatic brain injury (TBI) represents one of the most common worldwide causes of death and disability. Clinical and animal model studies have evidenced that TBI is characterized by the loss of both gray and white matter, resulting in brain atrophy and in a decrease in neurological function. Nowadays, no effective treatments to counteract TBI-induced neurological damage are available. Due to its complex and multifactorial pathophysiology (neuro-inflammation, cytotoxicity and astroglial scar formation), cell regeneration and survival in injured brain areas are strongly hampered. Recently, it has been proposed that adult neurogenesis may represent a new approach to counteract the post-traumatic neurodegeneration. In our laboratory, we have recently shown that physical exercise induces the long-lasting enhancement of subventricular (SVZ) adult neurogenesis in a p21 (negative regulator of neural progenitor proliferation)-null mice model, with a concomitant improvement of olfactory behavioral paradigms that are strictly dependent on SVZ neurogenesis. On the basis of this evidence, we have investigated the effect of running on SVZ neurogenesis and neurorepair processes in p21 knock-out mice that were subject to TBI at the end of a 12-day session of running. Our data indicate that runner p21 ko mice show an improvement in numerous post-trauma neuro-regenerative processes, including the following: (i) an increase in neuroblasts in the SVZ; (ii) an increase in the migration stream of new neurons from the SVZ to the damaged cortical region; (iii) an enhancement of new differentiating neurons in the peri-lesioned area; (iv) an improvement in functional recovery at various times following TBI. All together, these results suggest that a running-dependent increase in subventricular neural stem cells could represent a promising tool to improve the endogenous neuro-regenerative responses following brain trauma. Full article
(This article belongs to the Special Issue Molecular Research on Neural Stem Cells in Physiological and Pathological Condition)
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21 pages, 5009 KiB  
Article
Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells
by Kaoru Tominaga, Eiji Sakashita, Katsumi Kasashima, Kenji Kuroiwa, Yasumitsu Nagao, Naoki Iwamori and Hitoshi Endo
Int. J. Mol. Sci. 2023, 24(3), 2113; https://doi.org/10.3390/ijms24032113 - 20 Jan 2023
Cited by 5 | Viewed by 3392
Abstract
Epigenetic regulation via epigenetic factors in collaboration with tissue-specific transcription factors is curtail for establishing functional organ systems during development. Brain development is tightly regulated by epigenetic factors, which are coordinately activated or inactivated during processes, and their dysregulation is linked to brain [...] Read more.
Epigenetic regulation via epigenetic factors in collaboration with tissue-specific transcription factors is curtail for establishing functional organ systems during development. Brain development is tightly regulated by epigenetic factors, which are coordinately activated or inactivated during processes, and their dysregulation is linked to brain abnormalities and intellectual disability. However, the precise mechanism of epigenetic regulation in brain development and neurogenesis remains largely unknown. Here, we show that Tip60/KAT5 deletion in neural stem/progenitor cells (NSCs) in mice results in multiple abnormalities of brain development. Tip60-deficient embryonic brain led to microcephaly, and proliferating cells in the developing brain were reduced by Tip60 deficiency. In addition, neural differentiation and neuronal migration were severely affected in Tip60-deficient brains. Following neurogenesis in developing brains, gliogenesis started from the earlier stage of development in Tip60-deficient brains, indicating that Tip60 is involved in switching from neurogenesis to gliogenesis during brain development. It was also confirmed in vitro that poor neurosphere formation, proliferation defects, neural differentiation defects, and accelerated astrocytic differentiation in mutant NSCs are derived from Tip60-deficient embryonic brains. This study uncovers the critical role of Tip60 in brain development and NSC maintenance and function in vivo and in vitro. Full article
(This article belongs to the Special Issue Molecular Research on Neural Stem Cells in Physiological and Pathological Condition)
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Review

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13 pages, 581 KiB  
Review
Probing Interleukin-6 in Stroke Pathology and Neural Stem Cell Transplantation
by Gavin Miles Lockard, Adam Alayli, Molly Monsour, Jonah Gordon, Samantha Schimmel, Bassel Elsayed and Cesar V. Borlongan
Int. J. Mol. Sci. 2022, 23(24), 15453; https://doi.org/10.3390/ijms232415453 - 7 Dec 2022
Cited by 8 | Viewed by 2858
Abstract
Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3–4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction [...] Read more.
Stem cell transplantation is historically understood as a powerful preclinical therapeutic following stroke models. Current clinical strategies including clot busting/retrieval are limited by their time windows (tissue plasminogen activator: 3–4 h) and inevitable reperfusion injuries. However, 24+ h post-stroke, stem cells reduce infarction size, improve neurobehavioral performance, and reduce inflammatory agents including interleukins. Typically, interleukin-6 (IL-6) is regarded as proinflammatory, and thus, preclinical studies often discuss it as beneficial for neurological recuperation when stem cells reduce IL-6′s expression. However, some studies have also demonstrated neurological benefit with upregulation of IL-6 or preconditioning of stem cells with IL-6. This review specifically focuses on stem cells and IL-6, and their occasionally disparate, occasionally synergistic roles in the setting of ischemic cerebrovascular insults. Full article
(This article belongs to the Special Issue Molecular Research on Neural Stem Cells in Physiological and Pathological Condition)
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17 pages, 1058 KiB  
Review
NSC Physiological Features in Spinal Muscular Atrophy: SMN Deficiency Effects on Neurogenesis
by Raffaella Adami and Daniele Bottai
Int. J. Mol. Sci. 2022, 23(23), 15209; https://doi.org/10.3390/ijms232315209 - 2 Dec 2022
Cited by 5 | Viewed by 2769
Abstract
While the U.S. Food and Drug Administration and the European Medicines Evaluation Agency have recently approved new drugs to treat spinal muscular atrophy 1 (SMA1) in young patients, they are mostly ineffective in older patients since many motor neurons have already been lost. [...] Read more.
While the U.S. Food and Drug Administration and the European Medicines Evaluation Agency have recently approved new drugs to treat spinal muscular atrophy 1 (SMA1) in young patients, they are mostly ineffective in older patients since many motor neurons have already been lost. Therefore, understanding nervous system (NS) physiology in SMA patients is essential. Consequently, studying neural stem cells (NSCs) from SMA patients is of significant interest in searching for new treatment targets that will enable researchers to identify new pharmacological approaches. However, studying NSCs in these patients is challenging since their isolation damages the NS, making it impossible with living patients. Nevertheless, it is possible to study NSCs from animal models or create them by differentiating induced pluripotent stem cells obtained from SMA patient peripheral tissues. On the other hand, therapeutic interventions such as NSCs transplantation could ameliorate SMA condition. This review summarizes current knowledge on the physiological properties of NSCs from animals and human cellular models with an SMA background converging on the molecular and neuronal circuit formation alterations of SMA fetuses and is not focused on the treatment of SMA. By understanding how SMA alters NSC physiology, we can identify new and promising interventions that could help support affected patients. Full article
(This article belongs to the Special Issue Molecular Research on Neural Stem Cells in Physiological and Pathological Condition)
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