Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder

Corona, Juan Carlos

doi:10.3390/antiox9111039

Cited by 84 publications

(65 citation statements)

References 134 publications

(187 reference statements)

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“…Nowadays, there is increasing evidence that the aforementioned etiological factors and catecholaminergic dysfunction may lead to a neuronal state predominantly characterized by oxidative stress and inflammation, which could perpetuate the neurochemical alterations responsible for ADHD [ 124 ]. Increased levels of oxidative and nitrosative (NO) stress markers, together with a decrease in the concentrations of antioxidants, have been found in ADHD [ 125 , 126 ].…”

Section: Microbiota–gut–brain Axis and Attention-deficit And/or Hymentioning

confidence: 99%

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

et al. 2021

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Studies suggest that the bidirectional relationship existent between the gut microbiome (GM) and the central nervous system (CNS), or so-called the microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases in children and adults. In pediatric age, most studies have focused on patients with autism. However, evidence of the role played by the MGBA in attention deficit/hyperactivity disorder (ADHD), the most common neurodevelopmental disorder in childhood, is still scanty and heterogeneous. This review aims to provide the current evidence on the functioning of the MGBA in pediatric patients with ADHD and the specific role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in this interaction, as well as the potential of the GM as a therapeutic target for ADHD. We will explore: (1) the diverse communication pathways between the GM and the CNS; (2) changes in the GM composition in children and adolescents with ADHD and association with ADHD pathophysiology; (3) influence of the GM on the ω-3 PUFA imbalance characteristically found in ADHD; (4) interaction between the GM and circadian rhythm regulation, as sleep disorders are frequently comorbid with ADHD; (5) finally, we will evaluate the most recent studies on the use of probiotics in pediatric patients with ADHD.

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Section: Microbiota–gut–brain Axis and Attention-deficit And/or Hymentioning

confidence: 99%

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

et al. 2021

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“…Chronic pro-inflammatory immune dysregulation especially cellular mechanisms was considered to contribute to ADHD development ( Verlaet et al, 2014 ). Imbalance between oxidants and antioxidants, catecholaminergic dysregulation, medications, genetic and environmental factors could be producing neuroinflammation which further increased the ADHD symptoms as a result ( Corona, 2020 ). Besides, developmental or prenatal exposure to inflammation resulted in ADHD.…”

Section: Introductionmentioning

confidence: 99%

An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats

et al. 2021

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Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.

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“…Based on the key role of succinate in the Krebs cycle and in the respiratory chain, these results further support a dysfunctional brain energy metabolism in this animal model of ADHD. In addition, elevated succinate levels and mitochondrial dysfunctions have been associated to an increased oxidative stress, which has been extensively described in the brain of this animal model 34 , 35 , and in ADHD patients 36 – 39 . The higher brain levels of 2-ethylmalonate also observed in SHR/NCrl rats are consistent with an increased oxidative stress as it is a reliable lipid peroxidation biomarker 40 .…”

Section: Discussionmentioning

confidence: 81%

SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

et al. 2021

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Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.

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Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder

Cited by 84 publications

References 134 publications

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats

SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes

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