Oxidative Stress and Dietary Antioxidants in Neurological Diseases

Colin R Martin, Victor R Preedy, Colin R. Martin, Victor R. Preedy

• Publisher: Academic Press
• Year: 2020
• Print ISBN: 9780128177808
• eBook ISBN: 9780128177815
• Topic: Biowissenschaften
• Subtopic: Neurowissenschaft

Oxidative Stress and Dietary Antioxidants in Neurological Diseases provides an overview of oxidative stress in neurological diseases and associated conditions, including behavioral aspects and the potentially therapeutic usage of natural antioxidants in the diet. The processes within the science of oxidative stress are described in concert with other processes, such as apoptosis, cell signaling, and receptor mediated responses. This approach recognizes that diseases are often multifactorial and oxidative stress is a single component of this. The book examines basic processes of oxidative stress—from molecular biology to whole organs—relative to cellular defense systems, and across a range of neurological diseases.Sections discuss antioxidants in foods, including plants and components of the diet, examining the underlying mechanisms associated with therapeutic potential and clinical applications. Although some of this material is exploratory or preclinical, it can provide the framework for further in-depth analysis or studies via well-designed clinical trials or the analysis of pathways, mechanisms, and components in order to devise new therapeutic strategies. Very often oxidative stress is a feature of neurological disease and associated conditions which either centers on or around molecular and cellular processes. Oxidative stress can also arise due to nutritional imbalance during a spectrum of timeframes before the onset of disease or during its development.- Offers an overview of oxidative stress from molecular biology to whole organs- Discusses the potentially therapeutic usage of natural antioxidants in the patient diet- Provides the framework for further in-depth analysis or studies of potential treatments

Part I

Oxidative stress and neurological diseases

Chapter 1

The role of reactive oxygen species in the pathogenic pathways of depression

Masakazu Ibi; Chihiro Yabe-Nishimura Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Abstract

Psychiatric disorders may be “connectopathies” in neuronal connectivity. Major depressive disorder (MDD or depression) is one of the most prevalent mental disorders in our society. While involvement of genetic and environmental factors has been suggested in the pathophysiology of MDD, the exact molecular mechanism underlying the development of MDD has not been elucidated. Currently, altered neurotransmission, abnormality in the hypothalamus-pituitary-adrenal (HPA) axis, neuroinflammation, reduced neuroplasticity and network dysfunction are among the pathways implicated in the pathogenesis of MDD. Importantly, increased oxidative stress in depressed patients has been documented in previous clinical studies. Reactive oxygen species (ROS) are unstable small molecules that take part in various pathophysiological processes by interacting with proteins, lipids, and DNA. ROS therefore not only serve as signaling molecules, but also induce cellular damage. This chapter overviews the role of ROS in the development of depression, focusing on the redox modification of the pathogenic pathways leading to MDD.

Keywords

Brain-derived neurotrophic factor (BDNF); Depression; The hypothalamus-pituitary-adrenal (HPA) axis; Mitochondria; NADPH oxidase; Neuroinflammation; Neurotransmission; Reactive oxygen species (ROS)

Abbreviations

4-HNE 4-hydroxynonenal

8-OHdG 8-hydroxy-2′-deoxyguanosine

ACTH adrenocorticotropic hormone

ARE antioxidant responsive element

BBB blood-brain barrier

BDNF brain-derived neurotrophic factor

BH4 5,6,7,8-tetrahydrobiopterin

CEC cerebral endothelial cell

CREB cAMP response element-binding protein

CRH corticotropin-releasing hormone

DAMPs damage-associated molecular patterns

ETC electron transport chain

GPx glutathione peroxidase

GR glucocorticoid receptor

HPA hypothalamus-pituitary-adrenal

IDO indoleamine 2,3-dioxygenase

Keap1 Kelch-like ECH-associated protein1

NAcc nucleus accumbens

MAO monoamine oxidase

MDA malondialdehyde

MDD major depressive disorders

NMDA N-methyl-d-aspartate

Nrf2 NF-E2-related factor 2

OXPHOS oxidative phosphorylation

PAMPs pathogen-associated molecular patterns

PFC prefrontal cortex

PRR pattern recognition receptor

Prx peroxiredoxin

ROS reactive oxygen species

SOD superoxide dismutase

VTA ventral tegmental area

XO xanthine oxidase

Major depressive disorder (MDD or depression) is one of the most prevalent mental disorders in the world. Indeed, the lifetime prevalence rates range between 8% and 12%.¹ According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5),² a major depressive episode is defined as a period of more than 2 weeks during which either depressed mood or loss of interest in pleasure persists (i.e., anhedonia).

Compared with neurodegenerative disorders, there is no or little neuronal death in psychiatric disorders such as MDD. This finding makes it difficult for us to understand which brain region or neuronal circuit is responsible for the onset or development of depression. Because a disturbance in neurotransmission mediated by serotonin, noradrenaline, dopamine, and glutamate appears to take part in the pathogenesis, psychiatric disorders may be “connectopathies” in neuronal connectivity. An understanding of the difference in the brain network “connectome” between healthy subjects and patients suffering from psychosis may clarify the molecular mechanisms underlying psychiatric disorders. However, it may take some time until knowledge of all the neuronal circuits in human brain becomes available.

While the exact pathological pathway(s) leading to the development of MDD remains unsolved, the involvement of genetic and environmental factors has been suggested. Epidemiological research indicated that approximately 80% of the occurrence of bipolar disorder is attributed to genetic factors, while for depression, genetic factors comprise 30%–40%, illustrating the predominance of environmental factors.³ Among environmental factors, social stress elicits depressive symptoms and increases the vulnerability for MDD.

Based on previous experimental research, several pathways that are implicated in the pathogenesis of depression have been proposed. These are altered neurotransmission, abnormality in the HPA axis, neuroinflammation, reduced neuroplasticity, and network dysfunction. On the other hand, clinical studies demonstrated that increased oxidative stress in the peripheral tissues and brain of MDD patients. Excessive production of reactive oxygen species (ROS) thus appears to be associated with the development of MDD. ROS not only serve as signaling molecules, but also induce cellular damage by reacting with proteins, lipids, and DNA. This chapter overviews the current knowledge on the role of ROS in the development of depression, focusing on the redox modification of the pathogenic pathways leading to MDD.

Reactive oxygen species and antioxidant proteins

There are several lines of clinical evidence in which depression is characterized by a higher oxidative status and a disturbance in antioxidant mechanisms.⁴ In some cases, antioxidant defense molecules increase,⁵ which is considered a compensatory response to oxidative stress.

ROS are defined as chemically active species containing oxygen such as superoxide, peroxides, hydroxyl radical, and singlet oxygen. Superoxide anion is produced by one-electron reduction in O₂, and is produced mainly by flavoprotein, such as NADH dehydrogenase and CoQH₂ in mitochondria, and NADPH oxidase located in membranes (Fig. 1). Superoxide is rapidly converted to hydrogen peroxide (H₂O₂) by superoxide dismutase (SOD). H₂O₂ is reduced to H₂O by catalase, glutathione peroxidase (GPx), and peroxiredoxin (Prx). Catalase is a tetrameric heme protein localized in peroxisomes, while GPx and Prx, containing selenium in the active site, have peroxidase activity. After the reaction with H₂O₂, the oxidized GPx or Prx is reduced by glutathione or thioredoxin, respectively. Alternatively, H₂O₂ is further reduced to reactive hydroxyl radical in the presence of Fe^{2 +} (Fenton reaction).

Fig. 1 ROS and antioxidant proteins. In ROS-mediated pathologic pathways of depression, superoxide (O₂⁻) produced by NA...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• Foreword
• Preface
• Part I: Oxidative stress and neurological diseases
• Part II: Antioxidants and neurological diseases
• Index