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Neurons and Surrounding Environments in Neurological Disorders and Brain Damages

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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 (31 December 2020) | Viewed by 21034

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Special Issue Editors

Prof. Dr. Yunjong Lee

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Guest Editor

Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea
Interests: Parkinson’s disease; Animal model; High throughput screening; Diagnostic biomarkers; Neuroinflammation
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Seung Pil Yun

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Guest Editor

Department of Pharmacology, School of Medicine, Gyeongsang National University, 15 Jinjudae-ro 816, Jinju 52727, Korea
Interests: Neuro-iflammation; Neurodegenrative disease; Stem cell application for brain: Relationship CNS and peripheral organ inflammation; Brain cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Diverse neurological disorders as well as brain damage affect individuals tremendously by causing reversible or irreversible damage in neural circuits that are critically important for human behavior and healthy lifestyle. Recently, many researchers have reported significant pathological and physiological roles by multiple non-neuronal environments (neurotrophic and inflammatory factors by microglia-astrocytes, circulating metabolites by gut microbiota, infiltration of peripheral lymphocytes, brain tumors, etc.) in the maintenance of brain function. Novel therapeutic and diagnostic strategies for complex neurological disorders could be achieved by gaining a broad understanding of surrounding environments as well as neuronal alterations themselves.

In this regard, the aim of this Special Issue is to report the recent progress achieved from studies of the central nervous system influenced by various organ dysfunctions or peripheral pathological conditions, including cancers, and systemic inflammation. This Special Issue also welcomes translational and basic research on molecular alterations within neurons during diverse neurological problems.

Prof. Dr. Yunjong Lee
Prof. Dr. Seung Pil Yun
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

Neurological disorder
Alzheimer's disease
Parkinson's disease
Brain damage
Stroke
Cancer
Psychosis
Autism
Depression
Neurodegenerative biomarker
Organ dysfunctions
Systemic inflammation
Microglia
Astrocyte

Published Papers (6 papers)

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Research

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15 pages, 2829 KiB

Open AccessArticle

Neuroprotective Effect of Protaetia brevitarsis seulensis’ Water Extract on Trimethyltin-Induced Seizures and Hippocampal Neurodegeneration

by Sueun Lee, Young Hye Seo, Jun Ho Song, Wook Jin Kim, Ji Hye Lee, Byeong Cheol Moon, Mary Jasmin Ang, Sung Ho Kim, Changjong Moon, Jun Lee and Joong Sun Kim

Int. J. Mol. Sci. 2021, 22(2), 679; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020679 - 12 Jan 2021

Cited by 18 | Viewed by 2691

Abstract

This study aimed to investigate whether the Protaetia brevitarsis seulensis (PB)’ water extract (PBWE) ameliorates trimethyltin (TMT)-induced seizures and hippocampal neurodegeneration. To investigate the potential neuroprotective effect of the PBWE in vitro, a lactate dehydrogenase (LDH) assay was conducted in TMT-treated primary cultures of mouse hippocampal neurons. In TMT-treated adult C57BL/6 mice, behavioral and histopathological changes were evaluated by seizure scoring and Fluoro-Jade C staining, respectively. In our in vitro assay, we observed that pretreating mice hippocampal neuron cultures with the PBWE reduced TMT-induced cytotoxicity, as indicated by the decreased LDH release. Furthermore, pretreatment with the PBWE alleviated seizures and hippocampal neurodegeneration in TMT-treated mice. The antioxidant activity of the PBWE increased in a dose-dependent manner; moreover, pretreatment with the PBWE mitigated the TMT-induced Nrf2 stimulation. In addition, six major compounds, including adenine, hypoxanthine, uridine, adenosine, inosine, and benzoic acid, were isolated from the PBWE, and among them, inosine and benzoic acid have been confirmed to have an essential antioxidative activity. In conclusion, the PBWE ameliorated TMT-induced toxicity in hippocampal neurons in both in vitro and in vivo assays, through a potential antioxidative effect. Our findings suggest that the PBWE may have pharmacotherapeutic potential in neurodegenerative diseases such as seizures or epilepsy. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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15 pages, 3854 KiB

Open AccessArticle

Brain Endothelial P-Glycoprotein Level Is Reduced in Parkinson’s Disease via a Vitamin D Receptor-Dependent Pathway

by Hyojung Kim, Jeong-Yong Shin, Yun-Song Lee, Seung Pil Yun, Han-Joo Maeng and Yunjong Lee

Int. J. Mol. Sci. 2020, 21(22), 8538; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228538 - 12 Nov 2020

Cited by 26 | Viewed by 2738

Abstract

The progressive neurodegeneration in Parkinson’s disease (PD) is accompanied by neuroinflammation and endothelial vascular impairment. Although the vitamin D receptor (VDR) is expressed in both dopamine neurons and brain endothelial cells, its role in the regulation of endothelial biology has not been explored in the context of PD. In a 6-hydroxydopamine (6-OHDA)-induced PD mouse model, we observed reduced transcription of the VDR and its downstream target genes, CYP24 and MDR1a. The 6-OHDA-induced transcriptional repression of these genes were recovered after the VDR ligand—1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) treatment. Similarly, reduced vascular protein expression of P-glycoprotein (P-gp), encoded by MDR1a, after 6-OHDA administration was reversed by 1,25(OH)₂D₃. Moreover, marked reduction of endothelial P-gp expression with concomitant α-synuclein aggregation was found in a combinatorial AAV-αSyn/αSyn preformed fibril (PFF) injection mouse model and postmortem PD brains. Supporting the direct effect of α-synuclein aggregation on endothelial biology, PFF treatment of human umbilical vein endothelial cells (HUVECs) was sufficient to induce α-synuclein aggregation and repress transcription of the VDR. PFF-induced P-gp downregulation and impaired functional activity in HUVECs completely recovered after 1,25(OH)₂D₃ treatment. Taken together, our results suggest that a dysfunctional VDR-P-gp pathway could be a potential target for the maintenance of vascular homeostasis in PD pathological conditions. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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26 pages, 3726 KiB

Open AccessArticle

Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts

by Giulia Guarnieri, Erica Sarchielli, Paolo Comeglio, Erika Herrera-Puerta, Irene Piaceri, Benedetta Nacmias, Matteo Benelli, Gavin Kelsey, Mario Maggi, Pasquale Gallina, Gabriella Barbara Vannelli and Annamaria Morelli

Int. J. Mol. Sci. 2020, 21(17), 6128; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176128 - 25 Aug 2020

Cited by 17 | Viewed by 2938

Abstract

TNFα is the main proinflammatory cytokine implicated in the pathogenesis of neurodegenerative disorders, but it also modulates physiological functions in both the developing and adult brain. In this study, we investigated a potential direct role of TNFα in determining phenotypic changes of a recently established cellular model of human basal forebrain cholinergic neuroblasts isolated from the nucleus basalis of Meynert (hfNBMs). Exposing hfNBMs to TNFα reduced the expression of immature markers, such as nestin and β-tubulin III, and inhibited primary cilium formation. On the contrary, TNFα increased the expression of TNFα receptor TNFR2 and the mature neuron marker MAP2, also promoting neurite elongation. Moreover, TNFα affected nerve growth factor receptor expression. We also found that TNFα induced the expression of DNA-methylation enzymes and, accordingly, downregulated genes involved in neuronal development through epigenetic mechanisms, as demonstrated by methylome analysis. In summary, TNFα showed a dual role on hfNBMs phenotypic plasticity, exerting a negative influence on neurogenesis despite a positive effect on differentiation, through mechanisms that remain to be elucidated. Our results help to clarify the complexity of TNFα effects in human neurons and suggest that manipulation of TNFα signaling could provide a potential therapeutic approach against neurodegenerative disorders. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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19 pages, 4348 KiB

Open AccessArticle

The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents

by In Soo Ryu, Oc-Hee Kim, Young Eun Lee, Ji Sun Kim, Zhan-Hui Li, Tae Wan Kim, Ri-Na Lim, Young Ju Lee, Jae Hoon Cheong, Hee Jin Kim, Yong Sup Lee, Scott C. Steffensen, Bong Hyo Lee, Joung-Wook Seo and Eun Young Jang

Int. J. Mol. Sci. 2020, 21(13), 4631; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134631 - 29 Jun 2020

Cited by 7 | Viewed by 2855

Abstract

The dissociative anesthetic phencyclidine (PCP) and PCP derivatives, including 4′-F-PCP, are illegally sold and abused worldwide for recreational and non-medical uses. The psychopharmacological properties and abuse potential of 4′-F-PCP have not been fully characterized. In this study, we evaluated the psychomotor, rewarding, and reinforcing properties of 4′-F-PCP using the open-field test, conditioned place preference (CPP), and self-administration paradigms in rodents. Using Western immunoblotting, we also investigated the expression of dopamine (DA)-related proteins and DA-receptor-mediated downstream signaling cascades in the nucleus accumbens (NAc) of 4′-F-PCP-self-administering rats. Intraperitoneal administration of 10 mg/kg 4′-F-PCP significantly increased locomotor and rearing activities and increased CPP in mice. Intravenous administration of 1.0 mg/kg/infusion of 4′-F-PCP significantly enhanced self-administration during a 2 h session under fixed ratio schedules, showed a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement, and significantly altered the expression of DA transporter and DA D1 receptor in the NAc of rats self-administering 1.0 mg/kg 4′-F-PCP. Additionally, the expression of phosphorylated (p) ERK, pCREB, c-Fos, and FosB/ΔFosB in the NAc was significantly enhanced by 1.0 mg/kg 4′-F-PCP self-administration. Taken together, these findings suggest that 4′-F-PCP has a high potential for abuse, given its robust psychomotor, rewarding, and reinforcing properties via activation of DAergic neurotransmission and the downstream signaling pathways in the NAc. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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Review

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15 pages, 616 KiB

Open AccessReview

Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease

by Eunyoung Kim, Undarmaa Otgontenger, Ariunzaya Jamsranjav and Sang Seong Kim

Int. J. Mol. Sci. 2020, 21(18), 6676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186676 - 12 Sep 2020

Cited by 28 | Viewed by 5541

Abstract

The deterioration of neurons in Alzheimer’s disease (AD) arises from genetic, immunologic, and cellular factors inside the cortex. The traditional consensus of the amyloid-beta (Aβ) paradigm as a singular cause of AD has been under revision, with the accumulation of exploding neurobiological evidence. Among the multifaceted casualties of AD, the involvement of glia gains significance for its dynamic contribution to neurons, either in a neuroprotective or neurotoxic fashion. Basically, microglia and astrocytes contribute to neuronal sustainability by releasing neuroprotective cytokines, maintaining an adequate amount of glutamate in the synapse, and pruning excessive synaptic terminals. Such beneficial effects divert to the other detrimental cascade in chronic neuroinflammatory conditions. In this change, there are new discoveries of specific cytokines, microRNAs, and complementary factors. Previously unknown mechanisms of ion channels such as Kv1.3, Kir2.1, and HCN are also elucidated in the activation of microglia. The activation of glia is responsible for the excitotoxicity through the overflow of glutamate transmitter via mGluRs expressed on the membrane, which can lead to synaptic malfunction and engulfment. The communication between microglia and astrocytes is mediated through exosomes as well as cytokines, where numerous pieces of genetic information are transferred in the form of microRNAs. The new findings tell us that the neuronal environment in the AD condition is a far more complicated and dynamically interacting space. The identification of each molecule in the milieu and cellular communication would contribute to a better understanding of AD in the neurobiological perspective, consequently suggesting a possible therapeutic clue. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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16 pages, 1048 KiB

Open AccessReview

Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain

by Gyeong Joon Moon, Minsang Shin and Sang Ryong Kim

Int. J. Mol. Sci. 2020, 21(6), 2023; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062023 - 16 Mar 2020

Cited by 5 | Viewed by 3743

Abstract

Ras homolog protein enriched in brain (Rheb) is a key activator of mammalian target of rapamycin complex 1 (mTORC1). The activation of mTORC1 by Rheb is associated with various processes such as protein synthesis, neuronal growth, differentiation, axonal regeneration, energy homeostasis, autophagy, and amino acid uptake. In addition, Rheb–mTORC1 signaling plays a crucial role in preventing the neurodegeneration of hippocampal neurons in the adult brain. Increasing evidence suggests that the constitutive activation of Rheb has beneficial effects against neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our recent studies revealed that adeno-associated virus serotype 1 (AAV1) transduction with Rheb(S16H), a constitutively active form of Rheb, exhibits neuroprotective properties through the induction of various neurotrophic factors, promoting neurotrophic interactions between neurons and astrocytes in the hippocampus of the adult brain. This review provides compelling evidence for the therapeutic potential of AAV1–Rheb(S16H) transduction in the hippocampus of the adult brain by exploring its neuroprotective effects and mechanisms. Full article

(This article belongs to the Special Issue Neurons and Surrounding Environments in Neurological Disorders and Brain Damages)

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