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Functional Modification of Neuronal Networks

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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 (28 February 2021) | Viewed by 28635

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Assoc. Prof. Jakub Wlodarczyk

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Guest Editor

Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland
Interests: synaptic plasticity; neuropsychiatric diseases; dendritic spines; posttranslational modifications; extracellular matrix; serotonin receptors; fluorescence imaging; mass spectrometry

Special Issue Information

Dear Colleagues,

Cognitive processes, as well as neuropsychiatric diseases, involve functional modification of neuronal networks through the reorganization of existing synapses. The underlying mechanism of neuronal plasticity is complex and many aspects remain elusive. Recent studies have highlighted the importance of protein posttranslational modifications, e.g., S-palmitoylation, in physiology and in a broad spectrum of human diseases. S-palmitoylation reversibly modifies numerous classes of neuronal proteins, and, thus, it is necessary to understand the complexity and dynamics of synaptic proteins modifications under physiological and pathological context. The function of synaptic proteins, receptors, and ion channels can be also modulated by another posttranslational modification known as proteolysis, e.g., by extracellular matrix (ECM) proteases. Recent studies indicate the existence of a causal link between the components that are involved in regulating ECM, namely, cell adhesion molecules and ECM modifiers, and serotonin receptor-mediated signaling, highlighting the effect of these functional elements on neuronal network rewiring. Hence, in the Special Issue, we will focus on the role of posttranslational modifications of synaptic proteins under physiological stimuli and following pathological conditions. We will also assess the role of serotonin receptor-mediated signaling in the development and maintenance of pathophysiological conditions, suggesting serotonin receptors as targets for the treatment of neurodegenerative diseases.

Assoc. Prof. Jakub Wlodarczyk
Guest Editor

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Keywords

synaptic plasticity
neuropsychiatric diseases
posttranslational modifications
extracellular matrix
serotonin receptors

Published Papers (7 papers)

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Research

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23 pages, 3766 KiB

Open AccessArticle

Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

by Congshan Jiang, Thiago Arzua, Yasheng Yan and Xiaowen Bai

Int. J. Mol. Sci. 2021, 22(3), 1389; https://doi.org/10.3390/ijms22031389 - 30 Jan 2021

Cited by 5 | Viewed by 2111

Abstract

Sevoflurane, one of the most commonly used pediatric anesthetics, was found to cause developmental neurotoxicity. To understand specific risk groups and develop countermeasures, a better understanding of its mechanisms is needed. We hypothesize that, as in many other brain degeneration pathways, long non-coding RNAs (lncRNAs) are involved in the sevoflurane-induced neurotoxicity. Postnatal day 7 (PD7) mice were exposed to 3% sevoflurane for 6 h. To quantify neurotoxicity in these mice, we (1) detected neural apoptosis through analysis of caspase 3 expression level and activity and (2) assessed long-term learning ability via the Morris water maze at PD60. To elucidate specific mechanisms, profiles of 27,427 lncRNAs and 18,855 messenger RNAs (mRNAs) in mouse hippocampi were analyzed using microarray assays. Sevoflurane-induced abnormal lncRNA and mRNA expression-associated function pathways were predicted by bioinformatic analysis. We found that sevoflurane induced significant neurotoxicity, causing acute neuroapoptosis and abnormal expression of 148 mRNAs and 301 lncRNAs on PD7 in mouse hippocampus. Additionally, exposed mice exhibited impaired memory on PD60. Bioinformatic analysis predicted that the dysregulated mRNAs, which are highly correlated with their co-expressed dysregulated lncRNAs, might be involved in 34 neurodegenerative signaling pathways (e.g., brain cell apoptosis and intellectual developmental disorder). Our study reveals for the first time that neonatal exposure to 3% sevoflurane induces abnormal lncRNA and mRNA expression profiles. These dysregulated lncRNAs/mRNAs form wide molecular networks that might contribute to various functional neurological disease pathways in the hippocampus, resulting in the observed acute apoptosis and impaired long-term memory. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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10 pages, 731 KiB

Open AccessCommunication

Mitochondrial Membranes of Human SH-SY5Y Neuroblastoma Cells Express Serotonin 5-HT₇ Receptor

by Alessandra Tempio, Mauro Niso, Luna Laera, Lucia Trisolini, Maria Favia, Lucia Ciranna, Domenico Marzulli, Giuseppe Petrosillo, Ciro Leonardo Pierri, Enza Lacivita and Marcello Leopoldo

Int. J. Mol. Sci. 2020, 21(24), 9629; https://doi.org/10.3390/ijms21249629 - 17 Dec 2020

Cited by 4 | Viewed by 2743

Abstract

Mitochondria in neurons contribute to energy supply, the regulation of synaptic transmission, Ca²⁺ homeostasis, neuronal excitability, and stress adaptation. In recent years, several studies have highlighted that the neurotransmitter serotonin (5-HT) plays an important role in mitochondrial biogenesis in cortical neurons, and regulates mitochondrial activity and cellular function in cardiomyocytes. 5-HT exerts its diverse actions by binding to cell surface receptors that are classified into seven distinct families (5-HT1 to 5-HT7). Recently, it was shown that 5-HT3 and 5-HT4 receptors are located on the mitochondrial membrane and participate in the regulation of mitochondrial function. Furthermore, it was observed that activation of brain 5-HT7 receptors rescued mitochondrial dysfunction in female mice from two models of Rett syndrome, a rare neurodevelopmental disorder characterized by severe behavioral and physiological symptoms. Our Western blot analyses performed on cell-lysate and purified mitochondria isolated from neuronal cell line SH-SY5Y showed that 5-HT7 receptors are also expressed into mitochondria. Maximal binding capacity (Bmax) obtained by Scatchard analysis on purified mitochondrial membranes was 0.081 pmol/mg of 5-HT7 receptor protein. Lastly, we evaluated the effect of selective 5-HT7 receptor agonist LP-211 and antagonist (inverse agonist) SB-269970 on mitochondrial respiratory chain (MRC) cytochrome c oxidase activity on mitochondria from SH-SY5Y cells. Our findings provide the first evidence that 5-HT7 receptor is also expressed in mitochondria. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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15 pages, 3772 KiB

Open AccessArticle

Expression of Fbp2, a Newly Discovered Constituent of Memory Formation Mechanisms, Is Regulated by Astrocyte–Neuron Crosstalk

by Daria Hajka, Przemysław Duda, Olga Wójcicka, Dominika Drulis-Fajdasz, Dariusz Rakus and Agnieszka Gizak

Int. J. Mol. Sci. 2020, 21(18), 6903; https://doi.org/10.3390/ijms21186903 - 20 Sep 2020

Cited by 2 | Viewed by 3099

Abstract

Fbp2 (muscle isozyme of fructose 1,6-bisphosphatase) is a glyconeogenesis-regulating enzyme and a multifunctional protein indispensable for long-term potentiation (LTP) formation in the hippocampus. Here, we present evidence that expression of Fbp2 in murine hippocampal cell cultures is regulated by crosstalk between neurons and astrocytes. Co-culturing of the two cell types results in a decrease in Fbp2 expression in astrocytes, and its simultaneous increase in neurons, as compared to monocultures. These changes are regulated by paracrine signaling using extracellular vesicle (EV)-packed factors released to the culture medium. It is well accepted that astrocyte–neuron metabolic crosstalk plays a crucial role in shaping neuronal function, and recently we have suggested that Fbp2 is a hub linking neuronal signaling with redox and/or energetic state of brain during the formation of memory traces. Thus, our present results emphasize the importance of astrocyte–neuron crosstalk in the regulation of the cells’ metabolism and synaptic plasticity, and bring us one step closer to a mechanistic understanding of the role of Fbp2 in these processes. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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17 pages, 5634 KiB

Open AccessArticle

Involvement of Netrin/Unc-5 Interaction in Ciliary Beating and in Pattern Formation of the Ciliary Band-Associated Strand (CBAS) in the Sea Urchin, Hemicentrotus pulcherrimus

by Hideki Katow, Kouki Abe, Tomoko Katow, Hiromi Yoshida and Masato Kiyomoto

Int. J. Mol. Sci. 2020, 21(18), 6587; https://doi.org/10.3390/ijms21186587 - 9 Sep 2020

Cited by 1 | Viewed by 1826

Abstract

The GABAergic neural circuit is involved in the motile activities of both larval and juvenile sea urchins. Therefore, its function is inherited beyond metamorphosis, despite large scale remodeling of larval organs during that period. However, the initial neural circuit formation mechanism is not well understood, including how glutamate decarboxylase-expressing blastocoelar cells (GADCs) construct the neural circuit along the circumoral ciliary band (a ciliary band-associated strand, CBAS) on the larval body surface. In this study, using whole-mount immunohistochemistry and 3D reconstructed imaging, the ontogenic process of CBAS patterning was studied by focusing on Netrin and the interaction with its receptor, Unc-5. During the early 2-arm pluteus stage, a small number of GADCs egress onto the apical surface of the larval ectoderm. Then, they line up on the circumoral side of the ciliary band, and by being inserted by a further number of GADCs, form longer multicellular strands along the Netrin stripe. Application of a synthetic peptide, CRFNMELYKLSGRKSGGVC of Hp-Netrin, that binds to the immunoglobulin domain of Unc-5 during the prism stage, causes stunted CBAS formation due to inhibition of GADC egression. This also results in reduced ciliary beating. Thus, the Netrin/Unc-5 interaction is involved in the construction and function of the CBAS. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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23 pages, 3462 KiB

Open AccessArticle

Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype

by Huifangjie Li, William C. Knight, Pengfei Yang, Yingqiu Guo, Joel S. Perlmutter, John C. Morris, Randall J. Bateman, Tammie L. S. Benzinger and Jinbin Xu

Int. J. Mol. Sci. 2020, 21(17), 6047; https://doi.org/10.3390/ijms21176047 - 22 Aug 2020

Cited by 8 | Viewed by 2959

Abstract

We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson’s disease, Parkinson’s disease dementia, and Dementia with Lewy body), Alzheimer’s disease (AD), and control brains and genotyped for TSPO, TREM2, and bridging integrator 1 (BIN1) genes using single nucleotide polymorphisms (SNP) assays. TREM2 gene variants were absent across all samples. However, associations between TSPO and BIN1 gene polymorphisms and TSPO, MPO, TREM2, and PAR level variations were found. PAR levels reduced significantly in the caudate of LBDs. TSPO density and tau fibrils decreased remarkably in the striatum of LBDs but increased in AD. Oxidative damage, induced by misfolded tau proteins and dopamine metabolism, causes microglia dystrophy or senescence during the late stage of LBDs. Consequently, microglia dysfunction conversely reduces tau propagation. The G allele of the BIN1 gene is a potential risk factor for tauopathy. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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Review

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22 pages, 1844 KiB

Open AccessReview

Quantification of Dendritic Spines Remodeling under Physiological Stimuli and in Pathological Conditions

by Ewa Bączyńska, Katarzyna Karolina Pels, Subhadip Basu, Jakub Włodarczyk and Błażej Ruszczycki

Int. J. Mol. Sci. 2021, 22(8), 4053; https://doi.org/10.3390/ijms22084053 - 14 Apr 2021

Cited by 24 | Viewed by 9869

Abstract

Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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33 pages, 2617 KiB

Open AccessReview

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

by Hafza Wajeeha Ejaz, Wei Wang and Minglin Lang

Int. J. Mol. Sci. 2020, 21(20), 7660; https://doi.org/10.3390/ijms21207660 - 16 Oct 2020

Cited by 74 | Viewed by 5521

Abstract

Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein. Full article

(This article belongs to the Special Issue Functional Modification of Neuronal Networks)

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