Research

25 pages, 20401 KiB

Open AccessArticle

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure

by Chang-Jun Lee, Song-Hee Lee, Beom-Seok Kang, Min-Kyu Park, Hyun-Wook Yang, Seo-Young Woo, Se-Wan Park, Dong-Yeon Kim, Hyun-Ho Jeong, Won-Il Yang, A-Ra Kho, Bo-Young Choi, Hong-Ki Song, Hui-Chul Choi, Yeo-Jin Kim and Sang-Won Suh

Antioxidants 2024, 13(4), 389; https://doi.org/10.3390/antiox13040389 - 24 Mar 2024

Viewed by 858

Abstract

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca²⁺) and other metal ions, such as zinc (Zn²⁺) and [...] Read more.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca²⁺) and other metal ions, such as zinc (Zn²⁺) and magnesium (Mg²⁺), into the cytosol. This Ca²⁺ influx at the presynaptic terminal triggers the release of Zn²⁺ and glutamate to the postsynaptic terminal. Zn²⁺ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn²⁺ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn²⁺ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn²⁺ accumulation, oxidative stress, and neuronal death. Our findings show that AML’s LTCC inhibition decreased excessive Zn²⁺ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine’s potential as a therapeutic agent in seizure management and mitigating seizures’ detrimental effects. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

17 pages, 2602 KiB

Open AccessArticle

Modulation of Kynurenic Acid Production by N-acetylcysteine Prevents Cognitive Impairment in Adulthood Induced by Lead Exposure during Lactation in Mice

by Paulina Ovalle Rodríguez, Daniela Ramírez Ortega, Tonali Blanco Ayala, Gabriel Roldán Roldán, Gonzalo Pérez de la Cruz, Dinora Fabiola González Esquivel, Saúl Gómez-Manzo, Laura Sánchez Chapul, Aleli Salazar, Benjamín Pineda and Verónica Pérez de la Cruz

Antioxidants 2023, 12(12), 2035; https://doi.org/10.3390/antiox12122035 - 23 Nov 2023

Viewed by 804

Abstract

Lead (Pb²⁺) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and [...] Read more.

Lead (Pb²⁺) exposure during early life induces cognitive impairment, which was recently associated with an increase in brain kynurenic acid (KYNA), an antagonist of NMDA and alpha-7 nicotinic receptors. It has been described that N-acetylcysteine (NAC) favors an antioxidant environment and inhibits kynurenine aminotransferase II activity (KAT II, the main enzyme of KYNA production), leading to brain KYNA levels decrease and cognitive improvement. This study aimed to investigate whether the NAC modulation of the brain KYNA levels in mice ameliorated Pb²⁺-induced cognitive impairment. The dams were divided into four groups: Control, Pb²⁺, NAC, and Pb²⁺+NAC, which were given drinking water or 500 ppm lead acetate in the drinking water ad libitum, from 0 to 23 postnatal days (PNDs). The NAC and Pb²⁺+NAC groups were simultaneously fed NAC (350 mg/day) in their chow from 0 to 23 PNDs. At PND 60, the effect of the treatment with Pb²⁺ and in combination with NAC on learning and memory performance was evaluated. Immediately after behavioral evaluation, brain tissues were collected to assess the redox environment; KYNA and glutamate levels; and KAT II activity. The NAC treatment prevented the long-term memory deficit exhibited in the Pb²⁺ group. As expected, Pb²⁺ group showed redox environment alterations, fluctuations in glutamate levels, and an increase in KYNA levels, which were partially avoided by NAC co-administration. These results confirmed that the excessive KYNA levels induced by Pb²⁺ were involved in the onset of cognitive impairment and could be successfully prevented by NAC treatment. NAC could be a tool for testing in scenarios in which KYNA levels are associated with the induction of cognitive impairment. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

23 pages, 9631 KiB

Open AccessArticle

c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration

by Alexis Martinez, Cristian M. Lamaizon, Cristian Valls, Fabien Llambi, Nancy Leal, Patrick Fitzgerald, Cliff Guy, Marcin M. Kamiński, Nibaldo C. Inestrosa, Brigitte van Zundert, Gonzalo I. Cancino, Andrés E. Dulcey, Silvana Zanlungo, Juan J. Marugan, Claudio Hetz, Douglas R. Green and Alejandra R. Alvarez

Antioxidants 2023, 12(11), 2007; https://doi.org/10.3390/antiox12112007 - 16 Nov 2023

Viewed by 1372

Abstract

The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due [...] Read more.

The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

16 pages, 4002 KiB

Open AccessArticle

Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4

by Alejandra Palomino-Antolín, Céline Decouty-Pérez, Víctor Farré-Alins, Paloma Narros-Fernández, Ana Belen Lopez-Rodriguez, María Álvarez-Rubal, Inés Valencia, Francisco López-Muñoz, Eva Ramos, Antonio Cuadrado, Ana I. Casas, Alejandro Romero and Javier Egea

Antioxidants 2023, 12(9), 1729; https://doi.org/10.3390/antiox12091729 - 07 Sep 2023

Viewed by 1171

Abstract

The role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting [...] Read more.

The role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β and interleukin-18. We hypothesized that the interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and NADPH oxidase 4 (NOX4) may play a critical role in the activation of the NLRP3 inflammasome and subsequent inflammatory responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated with ATP, showing a significant reduction of IL1-β release in NOX4 and Nrf2 KO mice. Importantly, NOX4 inhibition using GKT136901 also reduced IL-1β release, as in NOX4 KO mixed glial cultures. Moreover, we measured NOX4 and NLRP3 expression in wild-type mixed glial cultures following LPS treatment, observing that both increased after TLR4 activation, while 24 h treatment with tert-butylhydroquinone, a potent Nrf2 inducer, significantly reduced NLRP3 expression. LPS administration resulted in significant cognitive impairment compared to the control group. Indeed, LPS also modified the expression of NLRP3 and NOX4 in mouse hippocampus. However, mice treated with GKT136901 after LPS impairment showed a significantly improved discrimination index and recovered the expression of inflammatory genes to normal levels compared with wild-type animals. Hence, we here validate NOX4 as a key player in NLRP3 inflammasome activation, suggesting NOX4 pharmacological inhibition as a potent therapeutic approach in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

20 pages, 4047 KiB

Open AccessArticle

Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day

by Priyanka N. Bushana, Michelle A. Schmidt, Kevin M. Chang, Trisha Vuong, Barbara A. Sorg and Jonathan P. Wisor

Antioxidants 2023, 12(5), 1124; https://doi.org/10.3390/antiox12051124 - 19 May 2023

Viewed by 11008

Abstract

Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive [...] Read more.

Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling this metabolic shift towards a reductive redox environment may be a central function of sleep. Therefore, biochemical manipulations that potentiate cellular antioxidant pathways may facilitate this function of sleep. N-acetylcysteine increases cellular antioxidant capacity by serving as a precursor to glutathione. In mice, we observed that intraperitoneal administration of N-acetylcysteine at a time of day when sleep drive is naturally high accelerated the onset of sleep and reduced NREMS delta power. Additionally, N-acetylcysteine administration suppressed slow and beta electroencephalographic (EEG) activities during quiet wake, further demonstrating the fatigue-inducing properties of antioxidants and the impact of redox balance on cortical circuit properties related to sleep drive. These results implicate redox reactions in the homeostatic dynamics of cortical network events across sleep/wake cycles, illustrating the value of timing antioxidant administration relative to sleep/wake cycles. A systematic review of the relevant literature, summarized herein, indicates that this “chronotherapeutic hypothesis” is unaddressed within the clinical literature on antioxidant therapy for brain disorders such as schizophrenia. We, therefore, advocate for studies that systematically address the relationship between the time of day at which an antioxidant therapy is administered relative to sleep/wake cycles and the therapeutic benefit of that antioxidant treatment in brain disorders. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

20 pages, 6162 KiB

Open AccessArticle

Distinct Roles of CK2- and AKT-Mediated NF-κB Phosphorylations in Clasmatodendrosis (Autophagic Astroglial Death) within the Hippocampus of Chronic Epilepsy Rats

by Ji-Eun Kim, Duk-Shin Lee, Tae-Hyun Kim, Hana Park and Tae-Cheon Kang

Antioxidants 2023, 12(5), 1020; https://doi.org/10.3390/antiox12051020 - 28 Apr 2023

Cited by 1 | Viewed by 1218

Abstract

The downregulation of glutathione peroxidase-1 (GPx1) plays a role in clasmatodendrosis (an autophagic astroglial death) in the hippocampus of chronic epilepsy rats. Furthermore, N-acetylcysteine (NAC, a GSH precursor) restores GPx1 expression in clasmatodendritic astrocytes and alleviates this autophagic astroglial death, independent of nuclear [...] Read more.

The downregulation of glutathione peroxidase-1 (GPx1) plays a role in clasmatodendrosis (an autophagic astroglial death) in the hippocampus of chronic epilepsy rats. Furthermore, N-acetylcysteine (NAC, a GSH precursor) restores GPx1 expression in clasmatodendritic astrocytes and alleviates this autophagic astroglial death, independent of nuclear factor erythroid-2-related factor 2 (Nrf2) activity. However, the regulatory signal pathways of these phenomena have not been fully explored. In the present study, NAC attenuated clasmatodendrosis by alleviating GPx1 downregulation, casein kinase 2 (CK2)-mediated nuclear factor-κB (NF-κB) serine (S) 529 and AKT-mediated NF-κB S536 phosphorylations. 2-[4,5,6,7-Tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazole-1-yl]acetic acid (TMCB; a selective CK2 inhibitor) relieved clasmatodendritic degeneration and GPx1 downregulation concomitant with the decreased NF-κB S529 and AKT S473 phosphorylations. In contrast, AKT inhibition by 3-chloroacetyl-indole (3CAI) ameliorated clasmatodendrosis and NF-κB S536 phosphorylation, while it did not affect GPx1 downregulation and CK2 tyrosine (Y) 255 and NF-κB S529 phosphorylations. Therefore, these findings suggest that seizure-induced oxidative stress may diminish GPx1 expression by increasing CK2-mediated NF-κB S529 phosphorylation, which would subsequently enhance AKT-mediated NF-κB S536 phosphorylation leading to autophagic astroglial degeneration. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

12 pages, 3297 KiB

Open AccessArticle

Human Microglia Synthesize Neurosteroids to Cope with Rotenone-Induced Oxidative Stress

by Chiara Lucchi, Alessandro Codeluppi, Monica Filaferro, Giovanni Vitale, Cecilia Rustichelli, Rossella Avallone, Jessica Mandrioli and Giuseppe Biagini

Antioxidants 2023, 12(4), 963; https://doi.org/10.3390/antiox12040963 - 19 Apr 2023

Cited by 3 | Viewed by 1419

Abstract

We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) [...] Read more.

We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) cell line. To this aim, HMC3 cultures were exposed to rotenone (100 nM) and neurosteroids were measured in the culture medium by liquid chromatography with tandem mass spectrometry. Microglia reactivity was evaluated by measuring interleukin 6 (IL-6) levels, whereas cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. After 24 h (h), rotenone increased IL-6 and reactive oxygen species levels by approximately +37% over the baseline, without affecting cell viability; however, microglia viability was significantly reduced at 48 h (p < 0.01). These changes were accompanied by the downregulation of several neurosteroids, including pregnenolone, pregnenolone sulfate, 5α-dihydroprogesterone, and pregnanolone, except for allopregnanolone, which instead was remarkably increased (p < 0.05). Interestingly, treatment with exogenous allopregnanolone (1 nM) efficiently prevented the reduction in HMC3 cell viability. In conclusion, this is the first evidence that human microglia can produce allopregnanolone and that this neurosteroid is increasingly released in response to oxidative stress, to tentatively support the microglia’s survival. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

16 pages, 3927 KiB

Open AccessArticle

Mild Traumatic Brain Injury Induces Mitochondrial Calcium Overload and Triggers the Upregulation of NCLX in the Hippocampus

by Rodrigo G. Mira, Rodrigo A. Quintanilla and Waldo Cerpa

Antioxidants 2023, 12(2), 403; https://doi.org/10.3390/antiox12020403 - 07 Feb 2023

Cited by 4 | Viewed by 1801

Abstract

Traumatic brain injury (TBI) is brain damage due to external forces. Mild TBI (mTBI) is the most common form of TBI, and repeated mTBI is a risk factor for developing neurodegenerative diseases. Several mechanisms of neuronal damage have been described in the cortex [...] Read more.

Traumatic brain injury (TBI) is brain damage due to external forces. Mild TBI (mTBI) is the most common form of TBI, and repeated mTBI is a risk factor for developing neurodegenerative diseases. Several mechanisms of neuronal damage have been described in the cortex and hippocampus, including mitochondrial dysfunction. However, up until now, there have been no studies evaluating mitochondrial calcium dynamics. Here, we evaluated mitochondrial calcium dynamics in an mTBI model in mice using isolated hippocampal mitochondria for biochemical studies. We observed that 24 h after mTBI, there is a decrease in mitochondrial membrane potential and an increase in basal matrix calcium levels. These findings are accompanied by increased mitochondrial calcium efflux and no changes in mitochondrial calcium uptake. We also observed an increase in NCLX protein levels and calcium retention capacity. Our results suggest that under mTBI, the hippocampal cells respond by incrementing NCLX levels to restore mitochondrial function. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

Review

Jump to: Research, Other

28 pages, 1377 KiB

Open AccessReview

Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury

by Hiren R. Modi, Sudeep Musyaju, Meaghan Ratcliffe, Deborah A. Shear, Anke H. Scultetus and Jignesh D. Pandya

Antioxidants 2024, 13(3), 303; https://doi.org/10.3390/antiox13030303 - 29 Feb 2024

Viewed by 1238

Abstract

Traumatic brain injury (TBI) is a major global health problem that affects both civilian and military populations worldwide. Post-injury acute, sub-acute, and chronic progression of secondary injury processes may contribute further to other neurodegenerative diseases. However, there are no approved therapeutic options available [...] Read more.

Traumatic brain injury (TBI) is a major global health problem that affects both civilian and military populations worldwide. Post-injury acute, sub-acute, and chronic progression of secondary injury processes may contribute further to other neurodegenerative diseases. However, there are no approved therapeutic options available that can attenuate TBI-related progressive pathophysiology. Recent advances in preclinical research have identified that mitochondria-centric redox imbalance, bioenergetics failure and calcium dysregulation play a crucial role in secondary injury progression after TBI. Mitochondrial antioxidants play an important role in regulating redox homeostasis. Based on the proven efficacy of preclinical and clinical compounds and targeting numerous pathways to trigger innate antioxidant defense, we may be able to alleviate TBI pathology progression by primarily focusing on preserving post-injury mitochondrial and cerebral function. In this review, we will discuss novel mitochondria-targeted antioxidant compounds, which offer a high capability of successful clinical translation for TBI management in the near future. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

26 pages, 3707 KiB

Open AccessReview

The Unfolded Protein Response: A Double-Edged Sword for Brain Health

by Magdalena Gebert, Jakub Sławski, Leszek Kalinowski, James F. Collawn and Rafal Bartoszewski

Antioxidants 2023, 12(8), 1648; https://doi.org/10.3390/antiox12081648 - 21 Aug 2023

Cited by 2 | Viewed by 1655

Abstract

Efficient brain function requires as much as 20% of the total oxygen intake to support normal neuronal cell function. This level of oxygen usage, however, leads to the generation of free radicals, and thus can lead to oxidative stress and potentially to age-related [...] Read more.

Efficient brain function requires as much as 20% of the total oxygen intake to support normal neuronal cell function. This level of oxygen usage, however, leads to the generation of free radicals, and thus can lead to oxidative stress and potentially to age-related cognitive decay and even neurodegenerative diseases. The regulation of this system requires a complex monitoring network to maintain proper oxygen homeostasis. Furthermore, the high content of mitochondria in the brain has elevated glucose demands, and thus requires a normal redox balance. Maintaining this is mediated by adaptive stress response pathways that permit cells to survive oxidative stress and to minimize cellular damage. These stress pathways rely on the proper function of the endoplasmic reticulum (ER) and the activation of the unfolded protein response (UPR), a cellular pathway responsible for normal ER function and cell survival. Interestingly, the UPR has two opposing signaling pathways, one that promotes cell survival and one that induces apoptosis. In this narrative review, we discuss the opposing roles of the UPR signaling pathways and how a better understanding of these stress pathways could potentially allow for the development of effective strategies to prevent age-related cognitive decay as well as treat neurodegenerative diseases. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Figure 1

Other

Jump to: Research, Review

22 pages, 702 KiB

Open AccessSystematic Review

Sleep Deprivation-Induced Oxidative Stress in Rat Models: A Scoping Systematic Review

by Vlad Sever Neculicioiu, Ioana Alina Colosi, Carmen Costache, Dan Alexandru Toc, Alexandra Sevastre-Berghian, Horațiu Alexandru Colosi and Simona Clichici

Antioxidants 2023, 12(8), 1600; https://doi.org/10.3390/antiox12081600 - 11 Aug 2023

Cited by 3 | Viewed by 3505

Abstract

Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist (inactivity, energy conservation, restoration, brain plasticity and antioxidant), multiple unknowns still remain regarding the proposed antioxidant roles of sleep. The existing [...] Read more.

Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist (inactivity, energy conservation, restoration, brain plasticity and antioxidant), multiple unknowns still remain regarding the proposed antioxidant roles of sleep. The existing experimental evidence is often contradicting, with studies pointing both toward and against the presence of oxidative stress after sleep deprivation. The main goals of this review were to analyze the existing experimental data regarding the relationship between sleep deprivation and oxidative stress, to attempt to further clarify multiple aspects surrounding this relationship and to identify current knowledge gaps. Systematic searches were conducted in three major online databases for experimental studies performed on rat models with oxidative stress measurements, published between 2015 and 2022. A total of 54 studies were included in the review. Most results seem to point to changes in oxidative stress parameters after sleep deprivation, further suggesting an antioxidant role of sleep. Alterations in these parameters were observed in both paradoxical and total sleep deprivation protocols and in multiple rat strains. Furthermore, the effects of sleep deprivation seem to extend beyond the central nervous system, affecting multiple other body sites in the periphery. Sleep recovery seems to be characterized by an increased variability, with the presence of both normalizations in some parameters and long-lasting changes after sleep deprivation. Surprisingly, most studies revealed the presence of a stress response following sleep deprivation. However, the origin and the impact of the stress response during sleep deprivation remain somewhat unclear. While a definitive exclusion of the influence of the sleep deprivation protocol on the stress response is not possible, the available data seem to suggest that the observed stress response may be determined by sleep deprivation itself as opposed to the experimental conditions. Due to this fact, the observed oxidative changes could be attributed directly to sleep deprivation. Full article

(This article belongs to the Special Issue Oxidative Stress in Brain Function)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Oxidative Stress in Brain Function

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI