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State-of-the-Art Molecular Neurobiology in Spain
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State-of-the-Art Molecular Neurobiology in Spain

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 March 2023) | Viewed by 15679

Special Issue Editors

Prof. Dr. Mario Diaz

E-Mail Website1 Website2
Guest Editor
Laboratory of Membrane Physiology and Biophysics, Departamento de Biología Animal, Edafología y Geología, Universidad de La Laguna, 38200 Santa Cruz de Tenerife, Spain
Interests: mechanisms of neurodegeneration; neuroprotection by polyunsaturated fatty acids and estrogens; neurochemistry of lipids; membrane physiology and membrane biophysics; physiological and pharmacological effects mediated by SERMs (selective estrogen receptor modulators)
Dr. Ander Matheu

E-Mail Website
Guest Editor
Cellular Oncology Group, Biodonostia Health Research Institute, E-20014 San Sebastian, Spain
Interests: stem cell biology; oncology; aging; frailty; neuroscience
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Isidro Ferrer

E-Mail Website1 Website2 Website3
Guest Editor
1. Departrment of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain
2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
Interests: aging; Alzheimer; Parkinson's disease; dementia with Lewy bodies; tau; alpha-synuclein; frontotemporal lobar degeneration (FTLD); amyotrophic lateral sclerosis; TDP43; prion diseases; vascular diseases; astroglia; oligodendroglia; microglia
Prof. Dr. Miguel Medina

E-Mail Website
Guest Editor
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain
Interests: Alzheimer's disease; dementia; neurodegeneration; tau; tauopathies; biomarkers; drug discovery

Special Issue Information

Dear Colleagues,

This Special Issue aims to provide a comprehensive overview of the recent advances in molecular neurobiology in Spain by inviting contributions from Spain research institutes/laboratories that consolidate our understanding in this area. Topics include, but are not limited to, the following:

  • Neurobiology;
  • Neurochemistry;
  • Neurology;
  • Neuropathology;
  • Neurophysiology;
  • Neuropharmacology;
  • Neurogenetics;
  • Neuro oncology;
  • Aging neuroscience.

Prof. Dr. Mario Diaz
Dr. Ander Matheu
Prof. Dr. Isidro Ferrer
Prof. Dr. Miguel Medina
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

  • neurobiology
  • neurochemistry
  • neurology
  • neuropathology
  • neurophysiology
  • neuropharmacology
  • neurogenetics
  • neuro oncology
  • aging neuroscience

Published Papers (6 papers)

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Research

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13 pages, 3868 KiB  
Article
Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
by Mònica Roldán, Gregorio Alexander Nolasco, Lluís Armengol, Marcos Frías, Marta Morell, Manel García-Aragonés, Florencia Epifani, Jordi Muchart, María Luisa Ramírez-Almaraz, Loreto Martorell, Cristina Hernando-Davalillo, Roser Urreizti and Mercedes Serrano
Int. J. Mol. Sci. 2023, 24(18), 13699; https://doi.org/10.3390/ijms241813699 - 5 Sep 2023
Viewed by 802
Abstract
The number of genes implicated in neurodevelopmental conditions is rapidly growing. Recently, variants in PPP2R1A have been associated with syndromic intellectual disability and a consistent, but still expanding, phenotype. The PPP2R1A gene encodes a protein subunit of the serine/threonine protein phosphatase 2A enzyme, [...] Read more.
The number of genes implicated in neurodevelopmental conditions is rapidly growing. Recently, variants in PPP2R1A have been associated with syndromic intellectual disability and a consistent, but still expanding, phenotype. The PPP2R1A gene encodes a protein subunit of the serine/threonine protein phosphatase 2A enzyme, which plays a critical role in cellular function. We report an individual showing pontocerebellar hypoplasia (PCH), microcephaly, optic and peripheral nerve abnormalities, and an absence of typical features like epilepsy and an abnormal corpus callosum. He bears an unreported variant in an atypical region of PPP2R1A. In silico studies, functional analysis using immunofluorescence, and super-resolution microscopy techniques were performed to investigate the pathogenicity of the variant. This analysis involved a comparative analysis of the patient’s fibroblasts with both healthy control cells and cells from an individual with the previously described phenotype. The results showed reduced expression of PPP2R1A and the presence of aberrant protein aggregates in the patient’s fibroblasts, supporting the pathogenicity of the variant. These findings suggest a potential association between PPP2R1A variants and PCH, expanding the clinical spectrum of PPP2R1A-related neurodevelopmental disorder. Further studies and descriptions of additional patients are needed to fully understand the genotype–phenotype correlation and the underlying mechanisms of this novel phenotype. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
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15 pages, 10179 KiB  
Article
A Novel Localization of METTL7A in Bergmann Glial Cells in Human Cerebellum
by América Vera-Montecinos, Jordi Galiano-Landeira, Mònica Roldán, Francisco Vidal-Domènech, Enrique Claro and Belén Ramos
Int. J. Mol. Sci. 2023, 24(9), 8405; https://doi.org/10.3390/ijms24098405 - 7 May 2023
Cited by 2 | Viewed by 1901
Abstract
Methyltransferase-like protein 7A (METTL7A) is a member of the METTL family of methyltransferases.Little information is available regarding the cellular expression of METTL7A in the brain. METTL7A is commonly located in the endoplasmic reticulum and to a lesser extent, in the lipid droplets of [...] Read more.
Methyltransferase-like protein 7A (METTL7A) is a member of the METTL family of methyltransferases.Little information is available regarding the cellular expression of METTL7A in the brain. METTL7A is commonly located in the endoplasmic reticulum and to a lesser extent, in the lipid droplets of some cells. Several studies have reported altered protein and RNA levels in different brain areas in schizophrenia. One of these studies found reduced protein levels of METTL7A in the cerebellar cortex in schizophrenia and stress murine models. Since there is limited information in the literature about METTL7A, we characterized its cellular and subcellular localizations in the human cerebellum using immunohistochemical analysis with laser confocal microscopy. Our study reveals a novel METTL7A localization in GFAP-positive cells, with higher expression in the end-feet of the Bergmann glia, which participate in the cerebrospinal fluid–brain parenchyma barrier. Further 3D reconstruction image analysis showed that METTL7A was expressed in the contacts between the Bergmann glia and Purkinje neurons. METTL7A was also detected in lipid droplets in some cells in the white matter. The localization of METTL7A in the human cerebellar glia limitans could suggest a putative role in maintaining the cerebellar parenchyma homeostasis and in the regulation of internal cerebellar circuits by modulating the synaptic activity of Purkinje neurons. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
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11 pages, 290 KiB  
Article
Association between LAG3/CD4 Genes Variants and Risk for Multiple Sclerosis
by Elena García-Martín, José A. G. Agúndez, Javier Gómez-Tabales, Julián Benito-León, Jorge Millán-Pascual, María Díaz-Sánchez, Patricia Calleja, Laura Turpín-Fenoll, Hortensia Alonso-Navarro, Esteban García-Albea, José Francisco Plaza-Nieto and Felix Javier Jiménez-Jiménez
Int. J. Mol. Sci. 2022, 23(23), 15244; https://doi.org/10.3390/ijms232315244 - 3 Dec 2022
Cited by 2 | Viewed by 1281
Abstract
Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have [...] Read more.
Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
24 pages, 2628 KiB  
Article
Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation
by Lucas Taoro-González, Daniel Pereda, Catalina Valdés-Baizabal, Miriam González-Gómez, José A. Pérez, Fátima Mesa-Herrera, Ana Canerina-Amaro, Herminia Pérez-González, Covadonga Rodríguez, Mario Díaz and Raquel Marin
Int. J. Mol. Sci. 2022, 23(13), 7430; https://doi.org/10.3390/ijms23137430 - 4 Jul 2022
Cited by 10 | Viewed by 2553
Abstract
Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling [...] Read more.
Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts’ integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice’s hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by “rejuvenating” the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
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Review

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20 pages, 1100 KiB  
Review
Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain
by Lucas E. Cabrera Zapata, Luis Miguel Garcia-Segura, María Julia Cambiasso and Maria Angeles Arevalo
Int. J. Mol. Sci. 2022, 23(20), 12288; https://doi.org/10.3390/ijms232012288 - 14 Oct 2022
Cited by 13 | Viewed by 6374
Abstract
For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years [...] Read more.
For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
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Other

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12 pages, 2368 KiB  
Case Report
Norovirus Intestinal Infection and Lewy Body Disease in an Older Patient with Acute Cognitive Impairment
by Manuel Moreno-Valladares, Veronica Moncho-Amor, Iraide Bernal-Simon, Eñaut Agirre-Iturrioz, María Álvarez-Satta and Ander Matheu
Int. J. Mol. Sci. 2022, 23(15), 8376; https://doi.org/10.3390/ijms23158376 - 29 Jul 2022
Cited by 2 | Viewed by 2065
Abstract
We present a case report on an older woman with unspecific symptoms and predominant long-term gastrointestinal disturbances, acute overall health deterioration with loss of autonomy for daily activities, and cognitive impairment. Autopsy revealed the presence of alpha-synuclein deposits spread into intestinal mucosa lesions, [...] Read more.
We present a case report on an older woman with unspecific symptoms and predominant long-term gastrointestinal disturbances, acute overall health deterioration with loss of autonomy for daily activities, and cognitive impairment. Autopsy revealed the presence of alpha-synuclein deposits spread into intestinal mucosa lesions, enteric plexuses, pelvic and retroperitoneal nerves and ganglia, and other organs as well as Lewy pathology in the central nervous system (CNS). Moreover, we isolated norovirus from the patient, indicating active infection in the colon and detected colocalization of norovirus and alpha-synuclein in different regions of the patient’s brain. In view of this, we report a concomitant norovirus infection with synthesis of alpha-synuclein in the gastrointestinal mucosa and Lewy pathology in the CNS, which might support Braak’s hypothesis about the pathogenic mechanisms underlying synucleinopathies. Full article
(This article belongs to the Special Issue State-of-the-Art Molecular Neurobiology in Spain)
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