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1.
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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2.
The impact of dietary macronutrient intake on cognitive function and the brain.
Muth, AK, Park, SQ
Clinical nutrition (Edinburgh, Scotland). 2021;(6):3999-4010
Abstract
Macronutrients - carbohydrates, fats, and proteins - supply the nutrients required for optimal functioning. Inadequate intake compromises both physical and brain health. We synthesized research on macronutrients from whole meals on cognitive function in healthy adults and identified underlying mechanisms. Intake of simple carbohydrates ('sugars') is consistently associated with decreased global cognition whereas consumption of complex carbohydrates correlates with successful brain aging and improved memory both in the short- and long-term. Saturated fatty acid intake correlates with decreased memory and learning scores whereas omega-3 intake correlates positively with memory scores. Protein intake boosts executive function and working memory when task-demands are high. Individual differences affecting the macronutrient-cognition relationship are age, physical activity, and glucose metabolism. Neural correlates reflect findings on cognitive functions: cortical thickness and cerebral amyloid burden correlate with sugar intake, inflammatory status and cerebral glucose metabolism correlate with fatty acid intake. Key mechanisms by which dietary macronutrients affect the brain and cognition include glucose and insulin metabolism, neurotransmitter actions, and cerebral oxidation and inflammation. In conclusion, macronutrient intake affects cognitive function both acutely and in the long-term, involving peripheral and central mechanisms. A healthy diet supports brain integrity and functionality, whereas inadequate nutrition compromises it. Studying diet can be key to nutritional recommendations, thereby improving the landscape of mental health and healthy brain aging.
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3.
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.
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4.
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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5.
Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children-An Update and Novel Insights.
Cohen Kadosh, K, Muhardi, L, Parikh, P, Basso, M, Jan Mohamed, HJ, Prawitasari, T, Samuel, F, Ma, G, Geurts, JM
Nutrients. 2021;(1)
Abstract
Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here, we show that the individual contribution of nutrients, their interaction with other micro- and macronutrients and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.
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6.
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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7.
Glutathione: An Old and Small Molecule with Great Functions and New Applications in the Brain and in Alzheimer's Disease.
Haddad, M, Hervé, V, Ben Khedher, MR, Rabanel, JM, Ramassamy, C
Antioxidants & redox signaling. 2021;(4):270-292
Abstract
Significance: Glutathione (GSH) represents the most abundant and the main antioxidant in the body with important functions in the brain related to Alzheimer's disease (AD). Recent Advances: Oxidative stress is one of the central mechanisms in AD. We and others have demonstrated the alteration of GSH levels in the AD brain, its important role in the detoxification of advanced glycation end-products and of acrolein, a by-product of lipid peroxidation. Recent in vivo studies found a decrease of GSH in several areas of the brain from control, mild cognitive impairment, and AD subjects, which are correlated with cognitive decline. Critical Issues: Several strategies were developed to restore its intracellular level with the l-cysteine prodrugs or the oral administration of γ-glutamylcysteine to prevent alterations observed in AD. To date, no benefit on GSH level or on oxidative biomarkers has been reported in clinical trials. Thus, it remains uncertain if GSH could be considered a potential preventive or therapeutic approach or a biomarker for AD. Future Directions: We address how GSH-coupled nanocarriers represent a promising approach for the functionalization of nanocarriers to overcome the blood/brain barrier (BBB) for the brain delivery of GSH while avoiding cellular toxicity. It is also important to address the presence of GSH in exosomes for its potential intercellular transfer or its shuttle across the BBB under certain conditions. Antioxid. Redox Signal. 35, 270-292.
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8.
Aging of Brain Related with Mitochondrial Dysfunctions.
Dhote, V, Samundre, P, Ganeshpurkar, A, Upaganlawar, A
Current drug targets. 2021;(14):1668-1687
Abstract
Advancing age presents a major challenge for the elderly population in terms of quality of life. The risk of cognitive impairment, motor in-coordination, and behavioral inconsistency due to neuronal damage is relatively higher in aging individuals of society. The brain, through its structural and functional integrity, regulates vital physiological events; however, the susceptibility of the brain to aging-related disturbances signals the onset of neurodegenerative diseases. Mitochondrial dysfunctions impair bioenergetic mechanism, synaptic plasticity, and calcium homeostasis in the brain, thus sufficiently implying mitochondria as a prime causal factor in accelerating aging-related neurodegeneration. We have reviewed the fundamental functions of mitochondria in a healthy brain and aimed to address the key issues in aging-related diseases by asking: 1) What goes wrong with mitochondria in the aging brain? 2) What are the implications of mitochondrial damage on motor functions and psychiatric symptoms? 3) How environmental chemicals and metabolic morbidities affect mitochondrial functions? Further, we share insights on opportunities and pitfalls in drug discovery approaches targeting mitochondria to slow down the progression of aging and related neurodegenerative diseases.
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9.
Novel therapeutic approaches for Parkinson's disease by targeting brain cholesterol homeostasis.
Pingale, TD, Gupta, GL
The Journal of pharmacy and pharmacology. 2021;(7):862-873
Abstract
OBJECTIVES Human brain is composed of 25% of the cholesterol & any dysfunction in brain cholesterol homeostasis contributes to neurodegenerative disorders such as Parkinson, Alzheimer's, Huntington's disease, etc. A growing literature indicates that alteration in neurotransmission & brain cholesterol metabolism takes place in the early stage of the disease. The current paper summarizes the role of cholesterol & its homeostasis in the pathophysiology of Parkinson's disease. KEY FINDINGS Literature findings suggest the possible role of lipids such as oxysterols, lipoproteins, etc. in Parkinson's disease pathophysiology. Cholesterol performs a diverse role in the brain but any deviation in its levels leads to neurodegeneration. Dysregulation of lipid caused by oxidative stress & inflammation leads to α-synuclein trafficking which contributes to Parkinson's disease progression. Also, α-synuclein by binding to membrane lipid forms lipid-protein complex & results in its aggregation. Different targets such as Phospholipase A2, Stearoyl-CoA desaturase enzyme, proprotein convertase subtilisin/kexin type 9, etc. have been identified as a potential novel approach for Parkinson's disease treatment. SUMMARY In the current review, we have discussed the possible molecular role of cholesterol homeostasis in Parkinson's disease progression. We also identified potential therapeutic targets that need to be evaluated clinically for the development of Parkinson's treatment.
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10.
A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota-Gut-Brain Axis in Satiety Regulation.
Pizarroso, NA, Fuciños, P, Gonçalves, C, Pastrana, L, Amado, IR
Nutrients. 2021;(2)
Abstract
Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota-gut-brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.