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Special Issue "Non-genetic Modifiers of Synaptic Plasticity and Neurotransmission in the Central Nervous System (CNS) in Health and Disease"

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: 31 July 2021.

Special Issue Editor

Dr. Andreas Grabrucker
E-Mail Website
Guest Editor
Cellular Neurobiology & Neuro-Nanotechnology lab, Department of Biological Sciences, University of Limerick

Special Issue Information

Dear Colleagues,

 Besides genetic factors, non-genetic factors influence how our brain develops and functions, influencing behavior and mental wellbeing. Despite an increasing understanding of how genes and their encoded proteins contribute to synaptic formation, plasticity, and function in the Central Nervous System, the interplay of non-genetic factors with these synaptic components remains poorly understood. However, both, genetic susceptibility and non-genetic factors affecting synapses may contribute to most brain disorders through a combination of disease-related gene variants and specific non-genetic factors that act as risk factors. This special issue focuses on the influence of non-genetic factors as modifiers of synaptic plasticity and neurotransmission in health and disease.

Recent advances in Eco-Neurobiology mean that we are now at a stage where it is feasible to start investigating the ways in which non-genetic factors act upon synapses on a mechanistic level. These factors (defined as “everything except that which is genetic”) include, but are not limited, to microbiota affecting synapses via the gut-brain axis, nutritional components such as lipids and trace metals, sex differences affecting synapse composition and function, immune diseases/ (neuro)inflammation, stress, drugs, or physical activity.

To understand gene-environment interaction on a molecular and mechanistic level, in vitro studies, studies using animal models, “omics” approaches or combinations of these may investigate processes such as alterations in synaptic gene expression, the synaptic proteome, synaptic signaling pathways, and synaptic activity, up to behavior.

Understanding how non-genetic factors contribute to synaptic dysfunction may lead to research strategies to normalize function in individuals with synaptopathies.

Dr. Andreas Grabrucker
Guest Editor

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 papers will be 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

  • Neuroinflammation
  • Stress, Nutrition
  • Microbiota
  • Environment
  • Lipids
  • Trace metals
  • synapses
  • synaptic transmission
  • drugs
  • physical activity
  • brain
  • gut-brain axis

Published Papers (2 papers)

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Research

Open AccessArticle
Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4
Int. J. Mol. Sci. 2021, 22(9), 4511; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094511 - 26 Apr 2021
Viewed by 257
Abstract
In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. [...] Read more.
In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses. Full article
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Open AccessArticle
Ketamine and Ro 25-6981 Reverse Behavioral Abnormalities in Rats Subjected to Dietary Zinc Restriction
Int. J. Mol. Sci. 2020, 21(13), 4791; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134791 - 06 Jul 2020
Cited by 1 | Viewed by 1199
Abstract
Clinical and preclinical studies indicate that zinc (Zn) is an essential factor in the development and treatment of major depressive disorder (MDD). Conventional monoamine-based antidepressants mobilize zinc in the blood and brain of depressed patients as well as rodents. N-methyl-D-aspartate acid receptor (NMDAR) [...] Read more.
Clinical and preclinical studies indicate that zinc (Zn) is an essential factor in the development and treatment of major depressive disorder (MDD). Conventional monoamine-based antidepressants mobilize zinc in the blood and brain of depressed patients as well as rodents. N-methyl-D-aspartate acid receptor (NMDAR) antagonists exhibit antidepressant-like activity. However, not much is known about the antidepressant efficacy of NMDAR antagonists in zinc-deficient (ZnD) animals. We evaluated the antidepressant-like activity of two NMDAR antagonists (ketamine; global NMDAR antagonist and Ro 25-6981 (Ro); selective antagonist of the GluN2B NMDAR subunit) in ZnD rats using the forced swim test (FST) and sucrose intake test (SIT). A single dose of either Ro 25-6981 or ketamine normalized depressive-like behaviors in ZnD rats; however, Ro was effective in both tests, while ketamine was only effective in the FST. Additionally, we investigated the mechanism of antidepressant action of Ro at the molecular (analysis of protein expression by Western blotting) and anatomical (density of dendritic spines by Golgi Cox-staining) levels. ZnD rats exhibited decreased phosphorylation of the p70S6K protein, and enhanced density of dendritic spines in the prefrontal cortex (PFC) compared to control rats. The antidepressant-like activity of Ro was associated with the increased phosphorylation of p70S6K and ERK in the PFC. In summary, single doses of the NMDAR antagonists ketamine and Ro exhibited antidepressant-like activity in the ZnD animal model of depression. Animals were only deprived of Zn for 4 weeks and the biochemical effects of Zn deprivation and Ro were investigated in the PFC and hippocampus. The shorter duration of dietary Zn restriction may be a limitation of the study. However, future studies with longer durations of dietary Zn restriction, as well as the investigation of multiple brain structures, are encouraged as a supplement to this study. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Identification and Regulation of Synaptic Zinc Transporters

Author: Andreas Grabrucker

Title: Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture
Authors: Xin Wu; Chenkai Wang; Kun Wang; Shuai Cui; Shengbin Wu; Meiqi Zhou
Affiliation: Research Institute of Acupuncture and Meridian, Anhui University of Chinese Medicine;Bozhou Institute of Chinese Medicine, Anhui Academy of Traditional Chinese Medicine
Abstract: Electroacupuncture (EA) alleviates acute myocardial ischemia(AMI) by altering the hippocampus. However, the molecular changes induced by EA are not known. We addressed this in the present study by hippocampus transcriptome profiling in a rat model of AMI following EA treatment.The rats were divided intosham(S), AMI(M), EA(E), AMI+EA+lesion (E+L) groups. Myocardial injury markers (ischemia-modified albumin, homocysteine and lipoprotein-associated phospholipase A2) in the serumwere downregulated in EA(P<0.05) compared to the M group and upregulated in E+L group(P<0.05)compared to E group. RNA sequencing analysis of the hippocampus revealed that the downregulation of 27 genes in M vs S as well as upregulation of 40 genes in M vs S were reversed by EA.These differentially expressed genes, which werevalidated by quantitative real-time PCR,wereenriched in 20 Kyoto Encyclopedia of Genes and Genomespathwaysrelated to glycerolipid,glycerophospholipid,and arachidonic acid metabolism as well asnervous system function(glutamatergic,cholinergic,serotonergic, GABAergic synapses).These results provide molecular-level evidencefor the therapeutic efficacy of EA in the treatment of AMI.

Title: Ketamine and Ro 25-6981 reverse behavioral abnormalities in rats subjected todietary zinc restriction
Authors: Bartłomiej Pochwat; Helena Domin; Anna Rafało-Ulińska; Bernadeta Szewczyk; Gabriel Nowak
Affiliation: Maj Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Trace Elements Neurobiology , Kraków , Poland
Abstract: Clinical and preclinical studies indicate that zinc (Zn) is an essential factor in the development and treatment of major depressive disorder (MDD). Accordingly, classic antidepressants are effective in zinc-deficient (ZnD) animals. However, not much is known about the antidepressant efficacy of NMDAR (N-methyl-D-aspartate acid receptor) antagonists in ZnD rats. We evaluated the antidepressant-like activity of single doses of ketamine and Ro 25-6981 (Ro) in ZnD animals using the forced swim test (FST) and sucrose intake test (SIT). Also, we investigated the mechanism of antidepressant action of Ro at the molecular (analysis of protein expression by Western blotting) and anatomical (density of dendritic spines by Golgi Cox-staining) levels. A single dose of either Ro 25-6981 or ketamine normalized depressive-like behaviors in ZnD rats. Additionally, ZnD rats exhibited decreased phosphorylation of the p70S6K protein, and enhanced density of dendritic spines in the prefrontal cortex (PFC) compared to control rats. The antidepressant-like activity of Ro is associated with increased phosphorylation of p70S6K and ERK in the PFC. In the present studies, we determined the efficacy of two NMDAR antagonists in rats subjected to 4 weeks of dietary Zn restriction. However, a longer duration of dietary Zn restriction and the Our results show that proper dietary Zn intake may be a critical factor in the prevention and treatment of MDD as a single dose of either Ro 25-6981 or ketamine exhibited antidepressant-like activity in the ZnD preclinical paradigm.

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