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Unveiling the Impact of Metabolism on Neuroscience

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 5200

Special Issue Editor


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Guest Editor
Department of Histology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Interests: blood brain barrier; water drainage; amyloid pathology; Alzheimer’s disease; stroke

Special Issue Information

Dear Colleagues,

Understanding the pathways of a balanced metabolism of neurons and glial cells is not only essential for understanding cognition and normal brain plasticity, but also for approaching any physiopathologic event linked to hypoxia and oxidative stress. As the brain tissue exhibits a particularly high demand for oxygen and glucose, an acute disruption of the blood supply leads within minutes to energy deficits in the affected brain regions. An ischemic stroke is therefore not only one of the major leading causes of death and invalidity worldwide, but also one of the most studied metabolic imbalance conditions within the CNS. Hypoxia and the accumulation of toxic metabolites lead to a loss of ion gradients and membrane potentials, in turn leading to cellular depolarisation, and depending on the extent and duration of energy deficiency, this translates into a neuronal and glial loss of function, and further on, into irreversible morphological changes, i.e., necrosis and apoptosis. The degradation of cellular membranes is also followed by the excessive release of glutamate, which together with an impaired glutamate reuptake promotes neuronal excitotoxicity and free radical-induced neuronal death. During aging, a decrease in glucose and oxygen metabolic rates occur at the level of neurons and glial cells, and this decrease is further accelerated in stroke and neurodegenerative diseases such as Alzheimer’s disease, Parkinson's, disease, Huntington’s disease, multiple sclerosis or amyotrophic lateral sclerosis. This Special Issue, entitled “Unveiling the Impact of Metabolism on Neuroscience”, is focused on the molecular mechanisms describing metabolic energy and glucose pathways in the nervous system, inhibitory/excitatory mediator balances, free radical production and impact, signaling factors promoting the survival or death of neurons and glial cells, and on the diffusion and drainage of any catabolites and solutes from the interstitial fluid through the perivascular spaces towards the lymphatics of the head and neck, in both normal conditions, aging, and in different pathologies, or in different cellular/animal models. Methodologically, this Special Issue welcomes articles that provide insights on the molecular neuropathology of stroke and neurodegenerative diseases, ion balance and Ca2+ signaling, mitochondrial molecular mechanisms, oxidative stress, the characterisation of the redox environment, the intake and utilisation of oxygen, glucose, water diffusion, macromolecule tracing, functional imaging and EEG reflected in molecular pathology and molecular neuropathology. Altogether, this Special Issue welcomes submissions of original research and review articles related to any aspect of the molecular mechanisms and pathogenesis of neurodegenerative diseases and stroke, as well as the follow-up and characterisation of novel biomarkers and treatment options.

Dr. Daniel Nicolae Pirici
Guest Editor

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Keywords

  • neurodegenerative diseases
  • stroke
  • molecular neuropathology
  • metabolomics
  • Ca2+ signaling
  • oxidative stress
  • water diffusion
  • macromolecule tracing

Published Papers (3 papers)

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Research

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14 pages, 2117 KiB  
Article
Effects of Osmotic Stress on the mRNA Expression of prl, prlr, gr, gh, and ghr in the Pituitary and Osmoregulatory Organs of Black Porgy, Acanthopagrus schlegelii
by Ganesan Nagarajan, Adimoolam Aruna, Yu-Ming Chang, Yousef Ahmed Alkhamis, Roshmon Thomas Mathew and Ching-Fong Chang
Int. J. Mol. Sci. 2023, 24(6), 5318; https://doi.org/10.3390/ijms24065318 - 10 Mar 2023
Cited by 1 | Viewed by 1331
Abstract
In euryhaline teleost black porgy, Acanthopagrus schlegelii, the glucocorticoid receptor (gr), growth hormone receptor (ghr), prolactin (prl)-receptor (prlr), and sodium–potassium ATPase alpha subunit (α-nka) play essential physiological roles in the osmoregulatory organs, [...] Read more.
In euryhaline teleost black porgy, Acanthopagrus schlegelii, the glucocorticoid receptor (gr), growth hormone receptor (ghr), prolactin (prl)-receptor (prlr), and sodium–potassium ATPase alpha subunit (α-nka) play essential physiological roles in the osmoregulatory organs, including the gill, kidney, and intestine, during osmotic stress. The present study aimed to investigate the impact of pituitary hormones and hormone receptors in the osmoregulatory organs during the transfer from freshwater (FW) to 4 ppt and seawater (SW) and vice versa in black porgy. Quantitative real-time PCR (Q-PCR) was carried out to analyze the transcript levels during salinity and osmoregulatory stress. Increased salinity resulted in decreased transcripts of prl in the pituitary, α-nka and prlr in the gill, and α-nka and prlr in the kidney. Increased salinity caused the increased transcripts of gr in the gill and α-nka in the intestine. Decreased salinity resulted in increased pituitary prl, and increases in α-nka and prlr in the gill, and α-nka, prlr, and ghr in the kidney. Taken together, the present results highlight the involvement of prl, prlr, gh, and ghr in the osmoregulation and osmotic stress in the osmoregulatory organs (gill, intestine, and kidney). Pituitary prl, and gill and intestine prlr are consistently downregulated during the increased salinity stress and vice versa. It is suggested that prl plays a more significant role in osmoregulation than gh in the euryhaline black porgy. Furthermore, the present results highlighted that the gill gr transcript’s role was solely to balance the homeostasis in the black porgy during salinity stress. Full article
(This article belongs to the Special Issue Unveiling the Impact of Metabolism on Neuroscience)
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19 pages, 3010 KiB  
Article
Investigating Therapeutic Effects of Indole Derivatives Targeting Inflammation and Oxidative Stress in Neurotoxin-Induced Cell and Mouse Models of Parkinson’s Disease
by Ya-Jen Chiu, Chih-Hsin Lin, Chung-Yin Lin, Pei-Ning Yang, Yen-Shi Lo, Yu-Chieh Chen, Chiung-Mei Chen, Yih-Ru Wu, Ching-Fa Yao, Kuo-Hsuan Chang and Guey-Jen Lee-Chen
Int. J. Mol. Sci. 2023, 24(3), 2642; https://doi.org/10.3390/ijms24032642 - 30 Jan 2023
Cited by 7 | Viewed by 2780
Abstract
Neuroinflammation and oxidative stress have been emerging as important pathways contributing to Parkinson’s disease (PD) pathogenesis. In PD brains, the activated microglia release inflammatory factors such as interleukin (IL)-β, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO), which increase oxidative stress and [...] Read more.
Neuroinflammation and oxidative stress have been emerging as important pathways contributing to Parkinson’s disease (PD) pathogenesis. In PD brains, the activated microglia release inflammatory factors such as interleukin (IL)-β, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO), which increase oxidative stress and mediate neurodegeneration. Using 1-methyl-4-phenylpyridinium (MPP+)-activated human microglial HMC3 cells and the sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we found the potential of indole derivative NC009-1 against neuroinflammation, oxidative stress, and neurodegeneration for PD. In vitro, NC009-1 alleviated MPP+-induced cytotoxicity, reduced NO, IL-1β, IL-6, and TNF-α production, and suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in MPP+-activated HMC3 cells. In vivo, NC009-1 ameliorated motor deficits and non-motor depression, increased dopamine and dopamine transporter levels in the striatum, and reduced oxidative stress as well as microglia and astrocyte reactivity in the ventral midbrain of MPTP-treated mice. These protective effects were achieved by down-regulating NLRP3, CASP1, iNOS, IL-1β, IL-6, and TNF-α, and up-regulating SOD2, NRF2, and NQO1. These results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanism, and indicate NC009-1 as a potential drug candidate for PD treatment. Full article
(This article belongs to the Special Issue Unveiling the Impact of Metabolism on Neuroscience)
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Review

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27 pages, 1364 KiB  
Review
Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson’s Disease
by Jasna Saponjic, Rebeca Mejías, Neda Nikolovski, Milorad Dragic, Asuman Canak, Stamatia Papoutsopoulou, Yasemin Gürsoy-Özdemir, Kari E. Fladmark, Panagiotis Ntavaroukas, Nuray Bayar Muluk, Milica Zeljkovic Jovanovic, Ángela Fontán-Lozano, Cristoforo Comi and Franca Marino
Int. J. Mol. Sci. 2024, 25(8), 4330; https://doi.org/10.3390/ijms25084330 - 14 Apr 2024
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Abstract
Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their [...] Read more.
Parkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results. Full article
(This article belongs to the Special Issue Unveiling the Impact of Metabolism on Neuroscience)
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