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Latest Advances in Neuroscience

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 (15 July 2023) | Viewed by 30664

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Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, 50121 Florence, Italy
Interests: electrophysiology; patch clamp; synaptic transmission; long term potentiation; immunocytochemistry; oxygen glucose deprivation; myelin; oligodendrocytes; brain ischemia; multiple sclerosis; adenosine receptors
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Special Issue Information

Dear Colleagues,

Significant progresses have been made in recent years in the field of neuroscience and neuropathology of the peripheral and central nervous system. Valuable contributions to present knowledge and its dissemination throughout the scientific community have been provided by numerous scientific societies and their regular meetings, even if by remote due to the actual pandemic state.

Among others, the present Special Issue takes encouragement from recent Congresses by the Italian Society for Neuroscience (SINS: 9-11th September 2021) and by the European Neurochemistry Society (ENS: S. Petersburg, 22-25th May 2022), but contributors from any other source are of course welcome.

Due to its inherent complexity, the human brain and spinal cord have long been studied via in vivo and in vitro animal models based on electrophysiological or biochemical issues as well as behavioral studies in primates and, also, humans. Efforts have been made to address neuroglial functions through a multifaceted perspective in order to outline physiological and l mechanisms of brain functions and their alteration in neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington diseases, multiple sclerosis, stroke, traumatic brain or spinal cord injury, aging, and so on.

This Special Issue encourages the submission of experimental articles, but review articles are also welcome. Contributions will be initially screened by the Editors for suitability/quality and then sent for peer review. As you might know, IJMS is an Open Access journal with IF=5.923 and publication charges (https://www.mdpi.com/journal/ijms/apc). Unfortunately, I cannot offer you a complete waiver of the publication costs, but I can offer a 200 CHF reduction of the fee. Besides, IJMS will supply a fast peer review service. All submitted papers would be published online quickly once accepted after peer review. Deadline is July 31th , 2022.

Please do not hesitate to contact me or Zurini Fu ([email protected]) in case you have any questions.


Dr. Elisabetta Coppi
Guest Editor

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Published Papers (5 papers)

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Research

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13 pages, 6626 KiB  
Article
Assembling Spheroids of Rat Primary Neurons Using a Stress-Free 3D Culture System
by Meaghan E. Harley-Troxell and Madhu Dhar
Int. J. Mol. Sci. 2023, 24(17), 13506; https://doi.org/10.3390/ijms241713506 - 31 Aug 2023
Cited by 1 | Viewed by 1768
Abstract
Neural injuries disrupt the normal functions of the nervous system, whose complexities limit current treatment options. Because of their enhanced therapeutic effects, neurospheres have the potential to advance the field of regenerative medicine and neural tissue engineering. Methodological steps can pose challenges for [...] Read more.
Neural injuries disrupt the normal functions of the nervous system, whose complexities limit current treatment options. Because of their enhanced therapeutic effects, neurospheres have the potential to advance the field of regenerative medicine and neural tissue engineering. Methodological steps can pose challenges for implementing neurosphere assemblies; for example, conventional static cultures hinder yield and throughput, while the presence of the necrotic core, time-consuming methodology, and high variability can slow their progression to clinical application. Here we demonstrate the optimization of primary neural cell-derived neurospheres, developed using a high-throughput, stress-free, 3D bioreactor. This process provides a necessary baseline for future studies that could develop co-cultured assemblies of stem cells combined with endothelial cells, and/or biomaterials and nanomaterials for clinical therapeutic use. Neurosphere size and neurite spreading were evaluated under various conditions using Image J software. Primary neural cells obtained from the hippocampi of three-day-old rat pups, when incubated for 24 h in a reactor coated with 2% Pluronic and seeded on Poly-D-Lysine-coated plates establish neurospheres suitable for therapeutic use within five days. Most notably, neurospheres maintained high cell viability of ≥84% and expressed the neural marker MAP2, neural marker β-Tubulin III, and glial marker GFAP at all time points when evaluated over seven days. Establishing these factors reduces the variability in developing neurospheres, while increasing the ease and output of the culture process and maintaining viable cellular constructs. Full article
(This article belongs to the Special Issue Latest Advances in Neuroscience)
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19 pages, 4289 KiB  
Article
Effects of Marginal Zn Excess and Thiamine Deficiency on Microglial N9 Cell Metabolism and Their Interactions with Septal SN56 Cholinergic Cells
by Anna Ronowska, Agnieszka Jankowska-Kulawy, Sylwia Gul-Hinc, Marlena Zyśk, Anna Michno and Andrzej Szutowicz
Int. J. Mol. Sci. 2023, 24(5), 4465; https://doi.org/10.3390/ijms24054465 - 24 Feb 2023
Cited by 3 | Viewed by 2168
Abstract
Mild thiamine deficiency aggravates Zn accumulation in cholinergic neurons. It leads to the augmentation of Zn toxicity by its interaction with the enzymes of energy metabolism. Within this study, we tested the effect of Zn on microglial cells cultivated in a thiamine-deficient medium, [...] Read more.
Mild thiamine deficiency aggravates Zn accumulation in cholinergic neurons. It leads to the augmentation of Zn toxicity by its interaction with the enzymes of energy metabolism. Within this study, we tested the effect of Zn on microglial cells cultivated in a thiamine-deficient medium, containing 0.003 mmol/L of thiamine vs. 0.009 mmol/L in a control medium. In such conditions, a subtoxic 0.10 mmol/L Zn concentration caused non-significant alterations in the survival and energy metabolism of N9 microglial cells. Both activities of the tricarboxylic acid cycle and the acetyl-CoA level were not decreased in these culture conditions. Amprolium augmented thiamine pyrophosphate deficits in N9 cells. This led to an increase in the intracellular accumulation of free Zn and partially aggravated its toxicity. There was differential sensitivity of neuronal and glial cells to thiamine-deficiency–Zn-evoked toxicity. The co-culture of neuronal SN56 with microglial N9 cells reduced the thiamine-deficiency–Zn-evoked inhibition of acetyl-CoA metabolism and restored the viability of the former. The differential sensitivity of SN56 and N9 cells to borderline thiamine deficiency combined with marginal Zn excess may result from the strong inhibition of pyruvate dehydrogenase in neuronal cells and no inhibition of this enzyme in the glial ones. Therefore, ThDP supplementation can make any brain cell more resistant to Zn excess. Full article
(This article belongs to the Special Issue Latest Advances in Neuroscience)
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12 pages, 1257 KiB  
Communication
Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes
by Matthew P. Lennol, Nicholas J. Ashton, Oscar Moreno-Pérez, María-Salud García-Ayllón, Jose-Manuel Ramos-Rincon, Mariano Andrés, José-Manuel León-Ramírez, Vicente Boix, Joan Gil, Kaj Blennow, Esperanza Merino, Henrik Zetterberg and Javier Sáez-Valero
Int. J. Mol. Sci. 2023, 24(3), 2715; https://doi.org/10.3390/ijms24032715 - 1 Feb 2023
Cited by 10 | Viewed by 2757
Abstract
The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS [...] Read more.
The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or “long COVID”), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms. Full article
(This article belongs to the Special Issue Latest Advances in Neuroscience)
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12 pages, 6377 KiB  
Article
Morpho-Functional Characterisation of the Rat Ventral Caudal Nerve in a Model of Axonal Peripheral Neuropathy
by Eleonora Pozzi, Laura Monza, Elisa Ballarini, Mario Bossi, Virginia Rodriguez-Menendez, Annalisa Canta, Alessia Chiorazzi, Valentina Alda Carozzi, Luca Crippa, Paola Marmiroli, Guido Cavaletti and Paola Alberti
Int. J. Mol. Sci. 2023, 24(2), 1687; https://doi.org/10.3390/ijms24021687 - 14 Jan 2023
Cited by 3 | Viewed by 1940
Abstract
Peripheral Neuropathies (PN) are common conditions whose treatment is still lacking in most cases. Animal models are crucial, but experimental procedures should be refined in some cases. We performed a detailed characterization of the ventral caudal nerve to contribute to a more effective [...] Read more.
Peripheral Neuropathies (PN) are common conditions whose treatment is still lacking in most cases. Animal models are crucial, but experimental procedures should be refined in some cases. We performed a detailed characterization of the ventral caudal nerve to contribute to a more effective assessment of axonal damage in future PN studies. PN was induced via weekly systemic injection of a neurotoxic drug (paclitaxel); we compared the control and PN-affected rats, performing serial neurophysiological evaluations of the caudal nerve for its entire length. On the same nerve portions, we performed light microscopy and ultrastructural pathological observations to assess the severity of damage and verify the integrity of the surrounding structures. Neurophysiological and morphological analyses confirmed that a severe axonopathy had ensued in the PN group, with a length-dependent modality, matching morphological observations. The site of neurophysiological recording (e.g., distance from the base of the tail) was critical for achieving useful data. A flexible experimental paradigm should be considered in animal studies investigating axonal PN, particularly if the expected severity is relevant; the mid-portion of the tail might be the most appropriate site: there damage might be remarkable but neither as extreme as at the tip of the tail nor as mild as at the base of the tail. Full article
(This article belongs to the Special Issue Latest Advances in Neuroscience)
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Review

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32 pages, 4436 KiB  
Review
Alzheimer’s Disease: Treatment Strategies and Their Limitations
by Elodie Passeri, Kamil Elkhoury, Margaretha Morsink, Kerensa Broersen, Michel Linder, Ali Tamayol, Catherine Malaplate, Frances T. Yen and Elmira Arab-Tehrany
Int. J. Mol. Sci. 2022, 23(22), 13954; https://doi.org/10.3390/ijms232213954 - 12 Nov 2022
Cited by 153 | Viewed by 20909
Abstract
Alzheimer’s disease (AD) is the most frequent case of neurodegenerative disease and is becoming a major public health problem all over the world. Many therapeutic strategies have been explored for several decades; however, there is still no curative treatment, and the priority remains [...] Read more.
Alzheimer’s disease (AD) is the most frequent case of neurodegenerative disease and is becoming a major public health problem all over the world. Many therapeutic strategies have been explored for several decades; however, there is still no curative treatment, and the priority remains prevention. In this review, we present an update on the clinical and physiological phase of the AD spectrum, modifiable and non-modifiable risk factors for AD treatment with a focus on prevention strategies, then research models used in AD, followed by a discussion of treatment limitations. The prevention methods can significantly slow AD evolution and are currently the best strategy possible before the advanced stages of the disease. Indeed, current drug treatments have only symptomatic effects, and disease-modifying treatments are not yet available. Drug delivery to the central nervous system remains a complex process and represents a challenge for developing therapeutic and preventive strategies. Studies are underway to test new techniques to facilitate the bioavailability of molecules to the brain. After a deep study of the literature, we find the use of soft nanoparticles, in particular nanoliposomes and exosomes, as an innovative approach for preventive and therapeutic strategies in reducing the risk of AD and solving problems of brain bioavailability. Studies show the promising role of nanoliposomes and exosomes as smart drug delivery systems able to penetrate the blood–brain barrier and target brain tissues. Finally, the different drug administration techniques for neurological disorders are discussed. One of the promising therapeutic methods is the intranasal administration strategy which should be used for preclinical and clinical studies of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Latest Advances in Neuroscience)
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