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1.
Neurodevelopmental effects of childhood malnutrition: A neuroimaging perspective.
Galler, JR, Bringas-Vega, ML, Tang, Q, Rabinowitz, AG, Musa, KI, Chai, WJ, Omar, H, Abdul Rahman, MR, Abd Hamid, AI, Abdullah, JM, et al
NeuroImage. 2021;:117828
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Abstract
Approximately one in five children worldwide suffers from childhood malnutrition and its complications, including increased susceptibility to inflammation and infectious diseases. Due to improved early interventions, most of these children now survive early malnutrition, even in low-resource settings (LRS). However, many continue to exhibit neurodevelopmental deficits, including low IQ, poor school performance, and behavioral problems over their lifetimes. Most studies have relied on neuropsychological tests, school performance, and mental health and behavioral measures. Few studies, in contrast, have assessed brain structure and function, and to date, these have mainly relied on low-cost techniques, including electroencephalography (EEG) and evoked potentials (ERP). The use of more advanced methods of neuroimaging, including magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), has been limited by cost factors and lack of availability of these technologies in developing countries, where malnutrition is nearly ubiquitous. This report summarizes the current state of knowledge and evidence gaps regarding childhood malnutrition and the study of its impact on neurodevelopment. It may help to inform the development of new strategies to improve the identification, classification, and treatment of neurodevelopmental disabilities in underserved populations at the highest risk for childhood malnutrition.
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Is microvascular dysfunction a systemic disorder with common biomarkers found in the heart, brain, and kidneys? - A scoping review.
Nowroozpoor, A, Gutterman, D, Safdar, B
Microvascular research. 2021;:104123
Abstract
Although microvascular dysfunction (MVD) has been well characterized in individual organs as different disease entities, clinical evidence is mounting in support of an underlying systemic process. To address this hypothesis, we systematically searched PubMed and Medline for studies in adults published between 2014 and 2019 that measured blood biomarkers of MVD in three vital organs i.e. brain, heart, and the kidney. Of the 9706 unique articles 321 met the criteria, reporting 49 biomarkers of which 16 were common to the three organs. Endothelial dysfunction, inflammation including reactive oxidation, immune activation, and coagulation were the commonly recognized pathways. Triglyceride, C-reactive protein, Cystatin C, homocysteine, uric acid, IL-6, NT-proBNP, thrombomodulin, von Willebrand Factor, and uric acid were increased in MVD of all three organs. In contrast, vitamin D was decreased. Adiponectin, asymmetric dimethylarginine, total cholesterol, high-density and low-density cholesterol were found to be variably increased or decreased in studies. We review the pathways underlying MVD in the three organs and summarize evidence supporting its systemic nature. This scoping review informs clinicians and researchers in the multi-system manifestation of MVD. Future work should focus on longitudinal investigations to evaluate the multi-system involvement of this disease.
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Neonatal Hypoglycemia and Brain Vulnerability.
De Angelis, LC, Brigati, G, Polleri, G, Malova, M, Parodi, A, Minghetti, D, Rossi, A, Massirio, P, Traggiai, C, Maghnie, M, et al
Frontiers in endocrinology. 2021;:634305
Abstract
Neonatal hypoglycemia is a common condition. A transient reduction in blood glucose values is part of a transitional metabolic adaptation following birth, which resolves within the first 48 to 72 h of life. In addition, several factors may interfere with glucose homeostasis, especially in case of limited metabolic stores or increased energy expenditure. Although the effect of mild transient asymptomatic hypoglycemia on brain development remains unclear, a correlation between severe and prolonged hypoglycemia and cerebral damage has been proven. A selective vulnerability of some brain regions to hypoglycemia including the second and the third superficial layers of the cerebral cortex, the dentate gyrus, the subiculum, the CA1 regions in the hippocampus, and the caudate-putamen nuclei has been observed. Several mechanisms contribute to neuronal damage during hypoglycemia. Neuronal depolarization induced by hypoglycemia leads to an elevated release of glutamate and aspartate, thus promoting excitotoxicity, and to an increased release of zinc to the extracellular space, causing the extensive activation of poly ADP-ribose polymerase-1 which promotes neuronal death. In this review we discuss the cerebral glucose homeostasis, the mechanisms of brain injury following neonatal hypoglycemia and the possible treatment strategies to reduce its occurrence.
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4.
Gut Microbiota and Neuroplasticity.
Murciano-Brea, J, Garcia-Montes, M, Geuna, S, Herrera-Rincon, C
Cells. 2021;(8)
Abstract
The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has led to a paradigm shift in the neurosciences. Understanding the neurobiological mechanisms supporting the relevance of actions mediated by the gut microbiota for brain physiology and neuronal functioning is a key research area. In this review, we discuss the literature showing how the microbiota is emerging as a key regulator of the brain's function and behavior, as increasing amounts of evidence on the importance of the bidirectional communication between the intestinal bacteria and the brain have accumulated. Based on recent discoveries, we suggest that the interaction between diet and the gut microbiota, which might ultimately affect the brain, represents an unprecedented stimulus for conducting new research that links food and mood. We also review the limited work in the clinical arena to date, and we propose novel approaches for deciphering the gut microbiota-brain axis and, eventually, for manipulating this relationship to boost mental wellness.
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5.
Gut-brain axis: A matter of concern in neuropsychiatric disorders…!
Naveed, M, Zhou, QG, Xu, C, Taleb, A, Meng, F, Ahmed, B, Zhang, Y, Fukunaga, K, Han, F
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110051
Abstract
The gut microbiota is composed of a large number of microbes, usually regarded as commensal bacteria. It has become gradually clear that gastrointestinal microbiota affects gut pathophysiology and the central nervous system (CNS) function by modulating the signaling pathways of the microbiota-gut-brain (MGB) axis. This bidirectional MGB axis communication primarily acts through neuroendocrine, neuroimmune, and autonomic nervous systems (ANS) mechanisms. Accumulating evidence reveals that gut microbiota interacts with the host brain, and its modulation may play a critical role in the pathology of neuropsychiatric disorders. Recently, neuroscience research has established the significance of gut microbiota in the development of brain systems that are essential to stress-related behaviors, including depression and anxiety. Application of modulators of the MGB, such as psychobiotics (e.g., probiotics), prebiotics, and specific diets, may be a promising therapeutic approach for neuropsychiatric disorders. The present review article primarily focuses on the relevant features of the disturbances of the MGB axis in the pathophysiology of neuropsychiatric disorders and its potential mechanisms.
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Emerging roles of oxidative stress in brain aging and Alzheimer's disease.
Ionescu-Tucker, A, Cotman, CW
Neurobiology of aging. 2021;:86-95
Abstract
Reactive oxygen species (ROS) are metabolic byproducts that are necessary for physiological function but can be toxic at high levels. Levels of these oxidative stressors increase gradually throughout the lifespan, impairing mitochondrial function and damaging all parts of the body, particularly the central nervous system. Emerging evidence suggests that accumulated oxidative stress may be one of the key mechanisms causing cognitive aging and neurodegenerative diseases such as Alzheimer's disease (AD). Here, we synthesize the current literature on the effect of neuronal oxidative stress on mitochondrial dysfunction, DNA damage and epigenetic changes related to cognitive aging and AD. We further describe how oxidative stress therapeutics such as antioxidants, caloric restriction and physical activity can reduce oxidation and prevent cognitive decline in brain aging and AD. Of the currently available therapeutics, we propose that long term physical activity is the most promising avenue for improving cognitive health by reducing ROS while promoting the low levels required for optimal function.
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Going with the grain: Fiber, cognition, and the microbiota-gut-brain-axis.
Berding, K, Carbia, C, Cryan, JF
Experimental biology and medicine (Maywood, N.J.). 2021;(7):796-811
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Abstract
Healthy dietary intake has been acknowledged for decades as one of the main contributors to health. More recently, the field of nutritional psychiatry has progressed our understanding regarding the importance of nutrition in supporting mental health and cognitive function. Thereby, individual nutrients, including omega-3 fatty acids and polyphenols, have been recognized to be key drivers in this relationship. With the progress in appreciating the influence of dietary fiber on health, increasingly research is focusing on deciphering its role in brain processes. However, while the importance of dietary fiber in gastrointestinal and metabolic health is well established, leading to the development of associated health claims, the evidence is not conclusive enough to support similar claims regarding cognitive function. Albeit the increasing knowledge of the impact of dietary fiber on mental health, only a few human studies have begun to shed light onto the underexplored connection between dietary fiber and cognition. Moreover, the microbiota-gut-brain axis has emerged as a key conduit for the effects of nutrition on the brain, especially fibers, that are acted on by specific bacteria to produce a variety of health-promoting metabolites. These metabolites (including short chain fatty acids) as well as the vagus nerve, the immune system, gut hormones, or the kynurenine pathway have been proposed as underlying mechanisms of the microbiota-brain crosstalk. In this minireview, we summarize the evidence available from human studies on the association between dietary fiber intake and cognitive function. We provide an overview of potential underlying mechanisms and discuss remaining questions that need to be answered in future studies. While this field is moving at a fast pace and holds promise for future important discoveries, especially data from human cohorts are required to further our understanding and drive the development of public health recommendations regarding dietary fiber in brain health.
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Cholesterol Metabolism in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.
Dai, L, Zou, L, Meng, L, Qiang, G, Yan, M, Zhang, Z
Molecular neurobiology. 2021;(5):2183-2201
Abstract
Cholesterol is an indispensable component of the cell membrane and plays vital roles in critical physiological processes. Brain cholesterol accounts for a large portion of total cholesterol in the human body, and its content must be tightly regulated to ensure normal brain function. Disorders of cholesterol metabolism in the brain are linked to neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and other atypical cognitive deficits that arise at old age. However, the specific role of cholesterol metabolism disorder in the pathogenesis of neurodegenerative diseases has not been fully elucidated. Statins that are a class of lipid-lowering drugs have been reported to have a positive effect on neurodegenerative diseases. Herein, we reviewed the physiological and pathological conditions of cholesterol metabolism and discussed the possible mechanisms of cholesterol metabolism and statin therapy in neurodegenerative diseases.
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Metabolic disorder in Alzheimer's disease.
Poddar, MK, Banerjee, S, Chakraborty, A, Dutta, D
Metabolic brain disease. 2021;(5):781-813
Abstract
Alzheimer's disease (AD), a well known aging-induced neurodegenerative disease is related to amyloid proteinopathy. This proteinopathy occurs due to abnormalities in protein folding, structure and thereby its function in cells. The root cause of such kind of proteinopathy and its related neurodegeneration is a disorder in metabolism, rather metabolomics of the major as well as minor nutrients. Metabolomics is the most relevant "omics" platform that offers a great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual's metabolome. In recent years, the research on such kinds of neurodegenerative diseases, especially aging-related disorders is broadened its scope towards metabolic function. Different neurotransmitter metabolisms are also involved with AD and its associated neurodegeneration. The genetic and epigenetic backgrounds are also noteworthy. In this review, the physiological changes of AD in relation to its corresponding biochemical, genetic and epigenetic involvements including its (AD) therapeutic aspects are discussed.
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Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome.
Forteza, F, Giorgini, G, Raymond, F
Cells. 2021;(4)
Abstract
Evidence suggesting the triangulation of the endocannabinoid system, exercise, and neurological health is emerging. In addition to the endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), the expanded endocannabinoid system, known as the endocannabinoidome (eCBome), appears to be an important player in this relationship. The eCBome includes several endocannabinoid-like mediators such as N-acylethanolamines and 2-monoacylglycerols, the enzymes involved in their biosynthesis and degradation, and the receptors they affect. This review aims to relate the functional interactions between aerobic exercise, and the molecular and cellular pathways related to endocannabinoids, in the hypothalamus, hippocampus, and the periphery, with special attention given to associations with emotional state, cognition, and mental health. Given the well-documented roles of many eCBome members in regulating stress and neurological processes, we posit that the eCBome is an important effector of exercise-induced central and peripheral adaptive mechanisms that benefit mental health. Gut microbiota imbalance, affecting the gut-brain axis and metabolism, also influences certain eCBome-modulated inflammation pathways. The integrity of the gut microbiota could thus be crucial in the onset of neuroinflammation and mental conditions. Further studies on how the modulation by exercise of the peripheral eCBome affects brain functions could reveal to be key elements in the prevention and treatment of neuropsychological disorders.