Topic Editors

Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche (CNR), Via U. La Malfa 153, 90146 Palermo, Italy
Istituto per la Ricerca e l’Innovazione Biomedica, CNR, via U. La Malfa 153, 90146 Palermo, Italy
Dipartmento di Biomedicina, Neuroscienze e Diagnostica avanzata (BIND), Università degli Studi di Palermo, Palermo, Italy
Departement of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Milan, Italy

Antioxidants and Oxidative Stress in Brain Health

Abstract submission deadline
closed (15 December 2022)
Manuscript submission deadline
closed (15 February 2023)
Viewed by
32756

Topic Information

Dear Colleagues,

Oxidative stress is defined as an imbalance in redox homeostasis, which leads to an accumulation of reactive oxygen/nitrogen species (ROS/RNS). Within certain limits, ROS can play important roles and work as secondary messengers, participating in the regulation of intracellular pathways. In physiological conditions, the deleterious effects of ROS production are efficiently neutralized by antioxidant pathways, which regulates oxygen consumption and redox generation capacity. Nevertheless, excess ROS can negatively influence the cells process, modulating the functions of nucleic acids, lipids, and proteins inducing inflammation, apoptosis, and autophagy, leading to organs/systems dysfunction, and allowing disease development and progression. In this context, the brain, with high-energy demand and weak antioxidant capacity, becomes an easy target of excessive oxidative insult. Brain oxidative homeostasis is essential for normal central nervous system (CNS) activity and is one of the key factors contributing to CNS impairment. When ROS production exceeds the scavenging capacity of the antioxidant response system, protein oxidation and lipid peroxidation occur, causing cellular degeneration and even functional decline. The consequences of excessive ROS production, such as mitochondrial dysfunction, apoptosis, and protein misfolding, are among the main therapeutic targets. In this scenario, synthetic antioxidants and phytochemicals, both extracts and pure compounds, have been identified as promising candidates in the prevention/treatment of neurological disorders. The mechanisms by which these compounds exert their beneficial effects are not yet fully understood.

Therefore, authors are invited to present original research articles, review papers, clinical case reports, or communications focused on the effects of natural and synthetic antioxidants at the CNS level. Chemical characterization of single compounds and extracts should be included, as well as their biological characterization with the investigation of their mechanism of action. Discussions of clinical aspects are welcome.

Dr. Domenico Nuzzo
Dr. Pasquale Picone
Dr. Valentina Di Liberto
Dr. Andrea Pinto
Topic Editors

Keywords

  • antioxidants
  • synthetic and semi-synthetic drugs
  • food and plant phytochemicals
  • oxidative stress
  • gut-brain axis
  • neurodegenerative diseases
  • psychological disorders
  • neurobiology
  • neuropharmacology
  • reactive oxygen and nitrogen species
  • mitochondrial dysfunction

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Antioxidants
antioxidants
7.0 8.8 2012 13.9 Days CHF 2900
Brain Sciences
brainsci
3.3 3.9 2011 15.6 Days CHF 2200
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900
NeuroSci
neurosci
- - 2020 20.4 Days CHF 1000

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Published Papers (12 papers)

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16 pages, 4326 KiB  
Article
Radical Scavenging Is Not Involved in Thymoquinone-Induced Cell Protection in Neural Oxidative Stress Models
by Christopher Krewenka, Sandra Rizzi, Chi Huu Nguyen, Marcin Delijewski, Lars Gille, Katrin Staniek, Johanna Catharina Duvigneau, Khaled Radad, Andrea Müllebner, Barbara Kranner and Rudolf Moldzio
Antioxidants 2023, 12(4), 858; https://doi.org/10.3390/antiox12040858 - 1 Apr 2023
Cited by 1 | Viewed by 1353
Abstract
Thymoquinone (TQ), an active compound from Nigella sativa seeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to [...] Read more.
Thymoquinone (TQ), an active compound from Nigella sativa seeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to reassess the radical scavenging properties of TQ and explore a potential mode of action. The effects of TQ were studied in models with mitochondrial impairment and oxidative stress induced by rotenone in N18TG2 neuroblastoma cells and rotenone/MPP+ in primary mesencephalic cells. Tyrosine hydroxylase staining revealed that TQ significantly protected dopaminergic neurons and preserved their morphology under oxidative stress conditions. Quantification of the formation of superoxide radicals via electron paramagnetic resonance showed an initial increase in the level of superoxide radicals in the cell by TQ. Measurements in both cell culture systems revealed that the mitochondrial membrane potential was tendentially lowered, while ATP production was mostly unaffected. Additionally, the total ROS levels were unaltered. In mesencephalic cell culture under oxidative stress conditions, caspase-3 activity was decreased when TQ was administered. On the contrary, TQ itself tremendously increased the caspase-3 activity in the neuroblastoma cell line. Evaluation of the glutathione level revealed an increased level of total glutathione in both cell culture systems. Therefore, the enhanced resistance against oxidative stress in primary cell culture might be a consequence of a lowered caspase-3 activity combined with an increased pool of reduced glutathione. The described anti-cancer ability of TQ might be a result of the pro-apoptotic condition in neuroblastoma cells. Our study provides evidence that TQ has no direct scavenging effect on superoxide radicals. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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26 pages, 2181 KiB  
Review
Plant-Based Antioxidants for Prevention and Treatment of Neurodegenerative Diseases: Phytotherapeutic Potential of Laurus nobilis, Aronia melanocarpa, and Celastrol
by Kristina Pilipović, Renata Jurišić Grubešić, Petra Dolenec, Natalia Kučić, Lea Juretić and Jasenka Mršić-Pelčić
Antioxidants 2023, 12(3), 746; https://doi.org/10.3390/antiox12030746 - 18 Mar 2023
Cited by 9 | Viewed by 3800
Abstract
With the progress of medicine, especially in the last century, life expectancy increased considerably. As a result, age-related diseases also increased, especially malignancies and degenerative diseases of the central nervous system. The incidence and prevalence of neurodegenerative diseases steadily increased over the years, [...] Read more.
With the progress of medicine, especially in the last century, life expectancy increased considerably. As a result, age-related diseases also increased, especially malignancies and degenerative diseases of the central nervous system. The incidence and prevalence of neurodegenerative diseases steadily increased over the years, but despite efforts to uncover the pathophysiological processes behind these conditions, they remain elusive. Among the many theories, oxidative stress was proposed to be involved in neurodegenerative processes and to play an important role in the morbidity and progression of various neurodegenerative disorders. Accordingly, a number of studies discovered the potential of natural plant constituents to have significant antioxidant activity. This review focused on several plant-based antioxidants that showed promising results in the prevention and treatment of neurodegenerative diseases. Laurus nobilis, Aronia melanocarpa, and celastrol, a chemical compound isolated from the root extracts of Tripterygium wilfordii and T. regelii, are all known to be rich in antioxidant polyphenols. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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17 pages, 6396 KiB  
Article
Manipulation of HSP70-SOD1 Expression Modulates SH-SY5Y Differentiation and Susceptibility to Oxidative Stress-Dependent Cell Damage: Involvement in Oxotremorine-M-Mediated Neuroprotective Effects
by Miriana Scordino, Monica Frinchi, Giulia Urone, Domenico Nuzzo, Giuseppa Mudò and Valentina Di Liberto
Antioxidants 2023, 12(3), 687; https://doi.org/10.3390/antiox12030687 - 10 Mar 2023
Cited by 6 | Viewed by 1979
Abstract
The differentiation of neural progenitors is a complex process that integrates different signals to drive transcriptional changes, which mediate metabolic, electrophysiological, and morphological cellular specializations. Understanding these adjustments is essential within the framework of stem cell and cancer research and therapy. Human neuroblastoma [...] Read more.
The differentiation of neural progenitors is a complex process that integrates different signals to drive transcriptional changes, which mediate metabolic, electrophysiological, and morphological cellular specializations. Understanding these adjustments is essential within the framework of stem cell and cancer research and therapy. Human neuroblastoma SH-SY5Y cells, widely used in neurobiology research, can be differentiated into neuronal-like cells through serum deprivation and retinoic acid (RA) supplementation. In our study, we observed that the differentiation process triggers the expression of Heat Shock Protein 70 (HSP70). Notably, inhibition of HSP70 expression by KNK437 causes a dramatic increase in cell death. While undifferentiated SH-SY5Y cells show a dose-dependent decrease in cell survival following exposure to hydrogen peroxide (H2O2), differentiated cells become resistant to H2O2-induced cell death. Interestingly, the differentiation process enhances the expression of SOD1 protein, and inhibition of HSP70 expression counteracts this effect and increases the susceptibility of differentiated cells to H2O2-induced cell death, suggesting that the cascade HSP70-SOD1 is involved in promoting survival against oxidative stress-dependent damage. Treatment of differentiated SH-SY5Y cells with Oxotremorine-M (Oxo), a muscarinic acetylcholine receptor agonist, enhances the expression of HSP70 and SOD1 and counteracts tert–Butyl hydroperoxide-induced cell death and reactive oxygen species (ROS) generation. It is worth noting that co-treatment with KNK437 reduces SOD1 expression and Oxo-induced protection against oxidative stress damage, suggesting the involvement of HSP70/SOD1 signaling in this beneficial effect. In conclusion, our findings demonstrate that manipulation of the HSP70 signal modulates SH-SY5Y differentiation and susceptibility to oxidative stress-dependent cell death and unravels novel mechanisms involved in Oxo neuroprotective functions. Altogether these data provide novel insights into the mechanisms underlying neuronal differentiation and preservation under stress conditions. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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17 pages, 4306 KiB  
Article
Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis
by Ying Chen, Katherine D. Holland, Howard G. Shertzer, Daniel W. Nebert and Timothy P. Dalton
Antioxidants 2023, 12(2), 448; https://doi.org/10.3390/antiox12020448 - 10 Feb 2023
Viewed by 1901
Abstract
Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. GclmKO knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; GclmKO mice exhibit 10–40% of normal tissue [...] Read more.
Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. GclmKO knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; GclmKO mice exhibit 10–40% of normal tissue GSH levels and show no overt phenotype. GuloKO knockout mice, lacking a functional Gulo gene encoding L-gulono-γ-lactone oxidase, cannot synthesize AA and depend on dietary ascorbic acid for survival. To elucidate functional crosstalk between GSH and AA in vivo, we generated the GclmKO/GuloKO double-knockout (DKO) mouse. DKO mice exhibited spontaneous epileptic seizures, proceeding to death between postnatal day (PND)14 and PND23. Histologically, DKO mice displayed neuronal loss and glial proliferation in the neocortex and hippocampus. Epileptic seizures and brain pathology in young DKO mice could be prevented with AA supplementation in drinking water (1 g/L). Remarkably, in AA-rescued adult DKO mice, the removal of AA supplementation for 2–3 weeks resulted in similar, but more severe, neocortex and hippocampal pathology and seizures, with death occurring between 12 and 21 days later. These results provide direct evidence for an indispensable, yet underappreciated, role for the interplay between GSH and AA in normal brain function and neuronal health. We speculate that the functional crosstalk between GSH and AA plays an important role in regulating glutamatergic neurotransmission and in protecting against excitotoxicity-induced brain damage. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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15 pages, 1861 KiB  
Review
Lipid Adaptations against Oxidative Challenge in the Healthy Adult Human Brain
by Mariona Jové, Natàlia Mota-Martorell, Èlia Obis, Joaquim Sol, Meritxell Martín-Garí, Isidre Ferrer, Manuel Portero-Otín and Reinald Pamplona
Antioxidants 2023, 12(1), 177; https://doi.org/10.3390/antiox12010177 - 12 Jan 2023
Cited by 4 | Viewed by 2139
Abstract
It is assumed that the human brain is especially susceptible to oxidative stress, based on specific traits such as a higher rate of mitochondrial free radical production, a high content in peroxidizable fatty acids, and a low antioxidant defense. However, it is also [...] Read more.
It is assumed that the human brain is especially susceptible to oxidative stress, based on specific traits such as a higher rate of mitochondrial free radical production, a high content in peroxidizable fatty acids, and a low antioxidant defense. However, it is also evident that human neurons, although they are post-mitotic cells, survive throughout an entire lifetime. Therefore, to reduce or avoid the impact of oxidative stress on neuron functionality and survival, they must have evolved several adaptive mechanisms to cope with the deleterious effects of oxidative stress. Several of these antioxidant features are derived from lipid adaptations. At least six lipid adaptations against oxidative challenge in the healthy human brain can be discerned. In this work, we explore the idea that neurons and, by extension, the human brain is endowed with an important arsenal of non-pro-oxidant and antioxidant measures to preserve neuronal function, refuting part of the initial premise. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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12 pages, 3807 KiB  
Article
Flow Synthesis of Nature-Inspired Mitochondria-Targeted Phenolic Derivatives as Potential Neuroprotective Agents
by Desirée Pecora, Francesca Annunziata, Sergio Pegurri, Pasquale Picone, Andrea Pinto, Domenico Nuzzo and Lucia Tamborini
Antioxidants 2022, 11(11), 2160; https://doi.org/10.3390/antiox11112160 - 31 Oct 2022
Viewed by 1674
Abstract
A series of phenolic derivatives designed to selectively target mitochondria were synthesized under flow conditions starting from natural phenolic acids. The two-step continuous flow protocol, performed in Cyrene, a bioavailable dipolar aprotic solvent, allowed the isolation of the MITO compounds in moderate to [...] Read more.
A series of phenolic derivatives designed to selectively target mitochondria were synthesized under flow conditions starting from natural phenolic acids. The two-step continuous flow protocol, performed in Cyrene, a bioavailable dipolar aprotic solvent, allowed the isolation of the MITO compounds in moderate to good yields. The MITO compounds obtained, as a first step, were tested for their safety by cell viability analysis. The cytocompatible dose, in human neuronal cell line SH-SH5Y, depends on the type of compound and the non-toxic dose is between 3.5 and 125 µM. Among the seven MITO compounds synthesized, two of them have shown interesting performances, being able to protect mitochondria from oxidative insult. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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18 pages, 4148 KiB  
Article
Leonurine Reduces Oxidative Stress and Provides Neuroprotection against Ischemic Injury via Modulating Oxidative and NO/NOS Pathway
by Ziteng Deng, Jiao Li, Xiaoquan Tang, Dan Li, Yazhou Wang, Shengxi Wu, Kai Fan and Yunfei Ma
Int. J. Mol. Sci. 2022, 23(17), 10188; https://doi.org/10.3390/ijms231710188 - 5 Sep 2022
Cited by 16 | Viewed by 2325
Abstract
Leonurine (Leo) has been found to have neuroprotective effects against cerebral ischemic injury. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. The aim of the present study was to investigate whether Leo could provide protection through the nitric oxide (NO)/nitric [...] Read more.
Leonurine (Leo) has been found to have neuroprotective effects against cerebral ischemic injury. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. The aim of the present study was to investigate whether Leo could provide protection through the nitric oxide (NO)/nitric oxide synthase (NOS) pathway. We firstly explored the effects of NO/NOS signaling on oxidative stress and apoptosis in in vivo and in vitro models of cerebral ischemia. Further, we evaluated the protective effects of Leo against oxygen and glucose deprivation (OGD)-induced oxidative stress and apoptosis in PC12 cells. We found that the rats showed anxiety-like behavior, and the morphology and number of neurons were changed in a model of photochemically induced cerebral ischemia. Both in vivo and in vitro results show that the activity of superoxide dismutase (SOD) and glutathione (GSH) contents were decreased after ischemia, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels were increased, indicating that cerebral ischemia induced oxidative stress and neuronal damage. Moreover, the contents of NO, total NOS, constitutive NOS (cNOS) and inducible NOS (iNOS) were increased after ischemia in rat and PC12 cells. Treatment with L-nitroarginine methyl ester (L-NAME), a nonselective NOS inhibitor, could reverse the change in NO/NOS expression and abolish these detrimental effects of ischemia. Leo treatment decreased ROS and MDA levels and increased the activity of SOD and GSH contents in PC12 cells exposed to OGD. Furthermore, Leo reduced NO/NOS production and cell apoptosis, decreased Bax expression and increased Bcl-2 levels in OGD-treated PC12 cells. All the data suggest that Leo protected against oxidative stress and neuronal apoptosis in cerebral ischemia by inhibiting the NO/NOS system. Our findings indicate that Leo could be a potential agent for the intervention of ischemic stroke and highlighted the NO/NOS-mediated oxidative stress signaling. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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20 pages, 2746 KiB  
Article
Antioxidant and Neuroprotective Effects of Paeonol against Oxidative Stress and Altered Carrier-Mediated Transport System on NSC-34 Cell Lines
by Sana Latif, Seung-Hye Choi, Asmita Gyawali, Seung Jae Hyeon, Young-Sook Kang and Hoon Ryu
Antioxidants 2022, 11(7), 1392; https://doi.org/10.3390/antiox11071392 - 18 Jul 2022
Cited by 10 | Viewed by 2266
Abstract
Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) motor neuron-like [...] Read more.
Paeonol is a naturally occurring phenolic agent that attenuates neurotoxicity in neurodegenerative diseases. We aimed to investigate the antioxidant and protective effects of paeonol and determine its transport mechanism in wild-type (WT; NSC-34/hSOD1WT) and mutant-type (MT; NSC-34/hSOD1G93A) motor neuron-like amyotrophic lateral sclerosis (ALS) cell lines. Cytotoxicity induced by glutamate, lipopolysaccharides, and H2O2 reduced viability of cell; however, the addition of paeonol improved cell viability against neurotoxicity. The [3H]paeonol uptake was increased in the presence of H2O2 in both cell lines. Paeonol recovered ALS model cell lines by reducing mitochondrial oxidative stress induced by glutamate. The transport of paeonol was time-, concentration-, and pH-dependent in both NSC-34 cell lines. Kinetic parameters showed two transport sites with altered affinity and capacity in the MT cell line compared to the WT cell line. [3H]Paeonol uptake increased in the MT cell line transfected with organic anion transporter1 (Oat1)/Slc22a6 small interfering RNA compared to that in the control. Plasma membrane monoamine transporter (Pmat) was also involved in the uptake of paeonol by ALS model cell lines. Overall, paeonol exhibits neuroprotective activity via a carrier-mediated transport system and may be a beneficial therapy for preventing motor neuronal damage under ALS-like conditions. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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15 pages, 3503 KiB  
Article
TNFα-Induced Oxidative Stress and Mitochondrial Dysfunction Alter Hypothalamic Neurogenesis and Promote Appetite Versus Satiety Neuropeptide Expression in Mice
by Mina Desai, Linsey Stiles, Adriana S. Torsoni, Marcio A. Torsoni, Orian S. Shirihai and Michael G. Ross
Brain Sci. 2022, 12(7), 900; https://doi.org/10.3390/brainsci12070900 - 9 Jul 2022
Cited by 2 | Viewed by 3501
Abstract
Maternal obesity results in programmed offspring hyperphagia and obesity. The increased offspring food intake is due in part to the preferential differentiation of hypothalamic neuroprogenitor cells (NPCs) to orexigenic (AgRP) vs. anorexigenic (POMC) neurons. The altered neurogenesis may involve hypothalamic bHLH (basic helix–loop–helix) [...] Read more.
Maternal obesity results in programmed offspring hyperphagia and obesity. The increased offspring food intake is due in part to the preferential differentiation of hypothalamic neuroprogenitor cells (NPCs) to orexigenic (AgRP) vs. anorexigenic (POMC) neurons. The altered neurogenesis may involve hypothalamic bHLH (basic helix–loop–helix) neuroregulatory factors (Hes1, Mash1, and Ngn3). Whilst the underlying mechanism remains unclear, it is known that mitochondrial function is critical for neurogenesis and is impacted by proinflammatory cytokines such as TNFα. Obesity is associated with the activation of inflammation and oxidative stress pathways. In obese pregnancies, increased levels of TNFα are seen in maternal and cord blood, indicating increased fetal exposure. As TNFα influences neurogenesis and mitochondrial function, we tested the effects of TNFα and reactive oxidative species (ROS) hydrogen peroxide (H2O2) on hypothalamic NPC cultures from newborn mice. TNFα treatment impaired NPC mitochondrial function, increased ROS production and NPC proliferation, and decreased the protein expression of proneurogenic Mash1/Ngn3. Consistent with this, AgRP protein expression was increased and POMC was decreased. Notably, treatment with H2O2 produced similar effects as TNFα and also reduced the protein expression of antioxidant SIRT1. The inhibition of STAT3/NFκB prevented the effects of TNFα, suggesting that TNFα mediates its effects on NPCs via mitochondrial-induced oxidative stress that involves both signaling pathways. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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11 pages, 581 KiB  
Communication
Polyphenols and IUGR Pregnancies: Effects of the Antioxidant Hydroxytyrosol on the Hippocampus Proteome in a Porcine Model
by Natalia Yeste, Jorge Pérez-Valle, Marta Vázquez-Gómez, Consolación García-Contreras, Antonio González-Bulnes and Anna Bassols
Antioxidants 2022, 11(6), 1135; https://doi.org/10.3390/antiox11061135 - 9 Jun 2022
Cited by 4 | Viewed by 2058
Abstract
Supplementation of a mother’s diet with antioxidants such as hydroxytyrosol (HTX) has been proposed to ameliorate the adverse phenotypes of foetuses affected by intrauterine growth restriction (IUGR). Our previous studies showed, in a porcine model of IUGR, an effect of maternal HTX supplementation [...] Read more.
Supplementation of a mother’s diet with antioxidants such as hydroxytyrosol (HTX) has been proposed to ameliorate the adverse phenotypes of foetuses affected by intrauterine growth restriction (IUGR). Our previous studies showed, in a porcine model of IUGR, an effect of maternal HTX supplementation on the neurotransmitter profile of several brain areas and the morphology of the hippocampus in 100 days old foetuses. The present study analyzed the impact of maternal HTX supplementation on the hippocampus proteome at this foetal age by TMT10plex labelling. Eleven differentially abundant proteins were identified by comparing both conditions, and eight of them downregulated and three upregulated in the HTX-treated group. The downregulated proteins were mainly involved in protein synthesis and RNA metabolism and may explain the differences in neuron differentiation in the HTX-treated group. The upregulated proteins were related to cell detoxification and could represent a potential mechanism to explain the neuroprotective effect of HTX. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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19 pages, 2629 KiB  
Article
Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer’s Disease
by Charleine Zussy, Rijo John, Théo Urgin, Léa Otaegui, Claire Vigor, Niyazi Acar, Geoffrey Canet, Mathieu Vitalis, Françoise Morin, Emmanuel Planel, Camille Oger, Thierry Durand, Shinde L. Rajshree, Laurent Givalois, Padma V. Devarajan and Catherine Desrumaux
Antioxidants 2022, 11(5), 838; https://doi.org/10.3390/antiox11050838 - 25 Apr 2022
Cited by 11 | Viewed by 3035
Abstract
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 n-3). In humans, low plasmatic concentrations of DHA have been associated [...] Read more.
Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 n-3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain. Several studies have reported reduced brain DHA concentrations in Alzheimer’s disease (AD) patients’ brains. Although a number of epidemiological studies suggest that dietary DHA consumption may protect the elderly from developing cognitive impairment or dementia including AD, several review articles report an inconclusive association between omega-3 PUFAs intake and cognitive decline. The source of these inconsistencies might be because DHA is highly oxidizable and its accessibility to the brain is limited by the blood–brain barrier. Thus, there is a pressing need for new strategies to improve DHA brain supply. In the present study, we show for the first time that the intranasal administration of nanovectorized DHA reduces Tau phosphorylation and restores cognitive functions in two complementary murine models of AD. These results pave the way for the development of a new approach to target the brain with DHA for the prevention or treatment of this devastating disease. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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16 pages, 1345 KiB  
Article
Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases
by Korina Karagianni, Spyros Pettas, Eirini Kanata, Elisavet Lioulia, Katrin Thune, Matthias Schmitz, Ioannis Tsamesidis, Evgenia Lymperaki, Konstantinos Xanthopoulos, Theodoros Sklaviadis and Dimitra Dafou
Antioxidants 2022, 11(4), 726; https://doi.org/10.3390/antiox11040726 - 6 Apr 2022
Cited by 12 | Viewed by 3469
Abstract
Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrPC) to the disease-associated (PrPSc). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and [...] Read more.
Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrPC) to the disease-associated (PrPSc). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have well-documented anti-oxidative and neuroprotective effects. Since oxidative stress plays an important role in the pathogenesis of prion diseases, we investigated the potential beneficial role of CA and CS in a cellular model of prion diseases (N2a22L cells) and in a cell-free prion amplification assay (RT-QuIC). The antioxidant effects of the compounds were confirmed when N2a22L were incubated with CA or CS. Furthermore, CA and CS reduced the accumulation of the disease-associated form of PrP, detected by Western Blotting, in N2a22L cells. This effect was validated in RT-QuIC assays, indicating that it is not associated with the antioxidant effects of CA and CS. Importantly, cell-free assays revealed that these natural products not only prevent the formation of PrP aggregates but can also disrupt already formed aggregates. Our results indicate that CA and CS have pleiotropic effects against prion diseases and could evolve into useful prophylactic and/or therapeutic agents against prion and other neurodegenerative diseases. Full article
(This article belongs to the Topic Antioxidants and Oxidative Stress in Brain Health)
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