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Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 May 2019) | Viewed by 34336

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Special Issue Editors

Prof. Dr. Kohji Fukunaga

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Guest Editor

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
Interests: CaMKI; neuropsychiatry disorders; drug addiction; neuroinflammation; dementia
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Feng Han

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Guest Editor

School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
Interests: molecular mechanisms of cerebrovascular diseases and potential drugable targets for pharmaceutical intervention; cerebrovascular biology and pathophysiological regulation of the cerebral microcirculation in brain diseases

Special Issue Information

Dear Colleagues,

Various kinds of neurons have to be generated and distributed in accurate numbers and to precise positions. To generate proper circuits, a huge number astrocytes, oligodendrocytes, and microglia are also located in precise regions to generate synapses. Especially, astrocytes communicate between neurons and blood vessels to transport oxygen and nutrients and to generate chemokines and cytokines to interfere with neurocircuits. Most of the processes in brain formation during embryonic periods are governed by genetic programs. In this Special Issue, we focus on 1) the critical roles of glial cells (astrocyte, oligodendrocytes, and microglia) to generate proper spines as environmental architecture. 2) How Ca2+ signaling is dysregulated to generate abnormal synaptic plasticity and spine formation in neuropsychiatry diseases. 3) How nutrients, such as DHA, EPA and arachidonic acid, affect neurogenesis and circuits to improve the psychiatry diseases. 4) How neuropsychiatry-related genes address abnormal spine formation and circuits in neuropsychiatry diseases in human.

The Special Issue contributes to the promotion of novel therapeutic approaches for the prevention and prediction of mental diseases, such as schizophrenia, autism and mental retardation.

Prof. Dr. Kohji Fukunaga
Prof. Dr. Feng Han
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

Neuronal Plasticity
Environmental Risk
Cytokines
Unsaturated Fatty Acids
Calcium Signal
Autism
Mental Retardation
Neutrients

Published Papers (5 papers)

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Research

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13 pages, 3190 KiB

Open AccessArticle

Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP⁺-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons

by Ichiro Kawahata, Luc Bousset, Ronald Melki and Kohji Fukunaga

Int. J. Mol. Sci. 2019, 20(21), 5358; https://doi.org/10.3390/ijms20215358 - 28 Oct 2019

Cited by 40 | Viewed by 4381

Abstract

α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson′s disease and other synucleinopathies. Fatty acids partially regulate α-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased α-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in α-Synuclein uptake, 1-methyl-4-phenylpyridinium (MPP⁺)-induced axodendritic retraction, and mitochondrial dysfunction. To disclose the issues, we employed cultured mesencephalic neurons derived from wild type or FABP3^−/− C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH⁺ neurons from FABP3^+/+ mice take up α-Synuclein monomers while FABP3^−/− TH⁺ neurons do not. The formation of filamentous α-Synuclein inclusions following treatment with MPP⁺ was observed only in FABP3^+/+, and not in FABP3^−/− neurons. Notably, detailed morphological analysis revealed that FABP^−/− neurons did not exhibit MPP⁺-induced axodendritic retraction. Moreover, FABP3 was also critical for MPP⁺-induced reduction of mitochondrial activity and the production of reactive oxygen species. These data indicate that FABP3 is critical for α-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson′s disease. Full article

(This article belongs to the Special Issue Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases)

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Review

Jump to: Research

20 pages, 1877 KiB

Open AccessReview

Clinical Therapeutic Strategy and Neuronal Mechanism Underlying Post-Traumatic Stress Disorder (PTSD)

by Yasushi Yabuki and Kohji Fukunaga

Int. J. Mol. Sci. 2019, 20(15), 3614; https://doi.org/10.3390/ijms20153614 - 24 Jul 2019

Cited by 19 | Viewed by 6686

Abstract

Post-traumatic stress disorder (PTSD) is characterized by an exaggerated response to contextual memory and impaired fear extinction, with or without mild cognitive impairment, learning deficits, and nightmares. PTSD is often developed by traumatic events, such as war, terrorist attack, natural calamities, etc. Clinical and animal studies suggest that aberrant susceptibility of emotion- and fear-related neurocircuits, including the amygdala, prefrontal cortex (PFC), and hippocampus may contribute to the development and retention of PTSD symptoms. Psychological and pharmacological therapy, such as cognitive behavioral therapy (CBT), and treatment with anti-depressive agents and/or antipsychotics significantly attenuate PTSD symptoms. However, more effective therapeutics are required for improvement of quality of life in PTSD patients. Previous studies have reported that ω3 long-chain polyunsaturated fatty acid (LCPUFA) supplements can suppress the development of PTSD symptoms. Fatty acid binding proteins (FABPs) are essential for LCPUFA intracellular trafficking. In this review, we have introduced Fabp3 null mice as an animal model of PTSD with impaired fear extinction. Moreover, we have addressed the neuronal circuits and novel therapeutic strategies for PTSD symptoms. Full article

(This article belongs to the Special Issue Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases)

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15 pages, 1306 KiB

Open AccessReview

Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology

by Sefan Asamitsu, Masayuki Takeuchi, Susumu Ikenoshita, Yoshiki Imai, Hirohito Kashiwagi and Norifumi Shioda

Int. J. Mol. Sci. 2019, 20(12), 2884; https://doi.org/10.3390/ijms20122884 - 13 Jun 2019

Cited by 42 | Viewed by 6386

Abstract

The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed. Recent bioinformatics analysis of the whole-genome and transcriptome obtained using G-quadruplex–specific antibodies and ligands, revealed genomic positions of G-quadruplexes. In addition, accumulating evidence pointed to the existence of these structures under physiologically- and pathologically-relevant conditions, with functional roles in vivo. In this review, we focused on DNA-G4 and RNA-G4, which may have important roles in neuronal function, and reveal mechanisms underlying neurological disorders related to synaptic dysfunction. In addition, we mention the potential of G-quadruplexes as therapeutic targets for neurological diseases. Full article

(This article belongs to the Special Issue Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases)

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17 pages, 253 KiB

Open AccessReview

Prevention or Amelioration of Autism-Like Symptoms in Animal Models: Will it Bring Us Closer to Treating Human ASD?

by Asher Ornoy, Liza Weinstein-Fudim and Zivanit Ergaz

Int. J. Mol. Sci. 2019, 20(5), 1074; https://doi.org/10.3390/ijms20051074 - 01 Mar 2019

Cited by 36 | Viewed by 6978

Abstract

Since the first animal model of valproic acid (VPA) induced autistic-like behavior, many genetic and non-genetic experimental animal models for Autism Spectrum Disorder (ASD) have been described. The more common non-genetic animal models induce ASD in rats and mice by infection/inflammation or the prenatal or early postnatal administration of VPA. Through the establishment of these models, attempts have been made to ameliorate or even prevent ASD-like symptoms. Some of the genetic models have been successfully treated by genetic manipulations or the manipulation of neurotransmission. Different antioxidants have been used (i.e., astaxanthin, green tea, piperine) to reduce brain oxidative stress in VPA-induced ASD models. Agents affecting brain neurotransmitters (donepezil, agmatine, agomelatine, memantine, oxytocin) also successfully reduced ASD-like symptoms. However, complete prevention of the development of symptoms was achieved only rarely. In our recent study, we treated mouse offspring exposed on postnatal day four to VPA with S-adenosine methionine (SAM) for three days, and prevented ASD-like behavior, brain oxidative stress, and the changes in gene expression induced by VPA. In this review, we describe, in addition to our data, the existing literature on the prevention/amelioration of ASD-like symptoms. We also discuss the possible mechanisms underlying some of these phenomena. Finally, we describe some of the clinical trials in children with ASD that were carried out as a result of data from animal studies, especially those with polyunsaturated fatty acids (PUFAs). Full article

(This article belongs to the Special Issue Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases)

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26 pages, 1036 KiB

Open AccessReview

Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer’s Disease (AD): A Systematic Review and Meta-Analysis

by Ted Kheng Siang Ng, Cyrus Su Hui Ho, Wilson Wai San Tam, Ee Heok Kua and Roger Chun-Man Ho

Int. J. Mol. Sci. 2019, 20(2), 257; https://doi.org/10.3390/ijms20020257 - 10 Jan 2019

Cited by 234 | Viewed by 9473

Abstract

Findings from previous studies reporting the levels of serum brain-derived neurotrophic factor (BDNF) in patients with Alzheimer’s disease (AD) and individuals with mild cognitive impairment (MCI) have been conflicting. Hence, we performed a meta-analysis to examine the aggregate levels of serum BDNF in patients with AD and individuals with MCI, in comparison with healthy controls. Fifteen studies were included for the comparison between AD and healthy control (HC) (n = 2067). Serum BDNF levels were significantly lower in patients with AD (SMD: −0.282; 95% confidence interval [CI]: −0.535 to −0.028; significant heterogeneity: I² = 83.962). Meta-regression identified age (p < 0.001) and MMSE scores (p < 0.001) to be the significant moderators that could explain the heterogeneity in findings in these studies. Additionally, there were no significant differences in serum BDNF levels between patients with AD and MCI (eight studies, n = 906) and between MCI and HC (nine studies, n = 5090). In all, patients with AD, but not MCI, have significantly lower serum BDNF levels compared to healthy controls. This meta-analysis confirmed the direction of change in serum BDNF levels in dementia. This finding suggests that a significant change in peripheral BDNF levels can only be detected at the late stage of the dementia spectrum. Molecular mechanisms, implications on interventional trials, and future directions for studies examining BDNF in dementia were discussed. Full article

(This article belongs to the Special Issue Environmental Risks for Aberrant Neuronal Plasticity in Neuropsychiatry Diseases)

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