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Mechanisms of Ageing and Development Dec 2021Brain aging is a complex process that affects everything from the subcellular to the organ level, begins early in life, and accelerates with age. Morphologically, brain... (Review)
Review
Brain aging is a complex process that affects everything from the subcellular to the organ level, begins early in life, and accelerates with age. Morphologically, brain aging is primarily characterized by brain volume loss, cortical thinning, white matter degradation, loss of gyrification, and ventricular enlargement. Pathophysiologically, brain aging is associated with neuron cell shrinking, dendritic degeneration, demyelination, small vessel disease, metabolic slowing, microglial activation, and the formation of white matter lesions. In recent years, the mechanics community has demonstrated increasing interest in modeling the brain's (bio)mechanical behavior and uses constitutive modeling to predict shape changes of anatomically accurate finite element brain models in health and disease. Here, we pursue two objectives. First, we review existing imaging-based data on white and gray matter atrophy rates and organ-level aging patterns. This data is required to calibrate and validate constitutive brain models. Second, we review the most critical cell- and tissue-level aging mechanisms that drive white and gray matter changes. We focuse on aging mechanisms that ultimately manifest as organ-level shape changes based on the idea that the integration of imaging and mechanical modeling may help identify the tipping point when normal aging ends and pathological neurodegeneration begins.
Topics: Aging; Atrophy; Brain; Cellular Senescence; Functional Neuroimaging; Humans; Models, Biological
PubMed: 34600936
DOI: 10.1016/j.mad.2021.111575 -
Physiological Reviews Apr 2022The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the brain is geared fully toward processing information and behaving,... (Review)
Review
The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the brain is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. The blood-brain barrier establishes a stable environment that is optimal for neuronal function, yet the barrier imposes a physiological problem; transcapillary filtration that forms extracellular fluid in other organs is reduced to a minimum in brain. Consequently, the brain depends on a special fluid [the cerebrospinal fluid (CSF)] that is flushed into brain along the unique perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined the term glymphatic system, based on its dependency on astrocytic vascular endfeet and their adluminal expression of aquaporin-4 water channels facing toward CSF-filled perivascular spaces. Glymphatic clearance of potentially harmful metabolic or protein waste products, such as amyloid-β, is primarily active during sleep, when its physiological drivers, the cardiac cycle, respiration, and slow vasomotion, together efficiently propel CSF inflow along periarterial spaces. The brain's extracellular space contains an abundance of proteoglycans and hyaluronan, which provide a low-resistance hydraulic conduit that rapidly can expand and shrink during the sleep-wake cycle. We describe this unique fluid system of the brain, which meets the brain's requisites to maintain homeostasis similar to peripheral organs, considering the blood-brain-barrier and the paths for formation and egress of the CSF.
Topics: Amyloid beta-Peptides; Biological Transport; Blood-Brain Barrier; Brain; Cerebrospinal Fluid; Glymphatic System; Humans
PubMed: 33949874
DOI: 10.1152/physrev.00031.2020 -
Neural Plasticity 2021The blood-brain barrier (BBB) is a semipermeable and extremely selective system in the central nervous system of most vertebrates, that separates blood from the brain's... (Review)
Review
The blood-brain barrier (BBB) is a semipermeable and extremely selective system in the central nervous system of most vertebrates, that separates blood from the brain's extracellular fluid. It plays a vital role in regulating the transport of necessary materials for brain function, furthermore, protecting it from foreign substances in the blood that could damage it. In this review, we searched in Google Scholar, Pubmed, Web of Science, and Saudi Digital Library for the various cells and components that support the development and function of this barrier, as well as the different pathways to transport the various molecules between blood and the brain. We also discussed the aspects that lead to BBB dysfunction and its neuropathological consequences, with the identification of some of the most important biomarkers that might be used as a biomarker to predict the BBB disturbances. This comprehensive overview of BBB will pave the way for future studies to focus on developing more specific targeting systems in material delivery as a future approach that assists in combinatorial therapy or nanotherapy to destroy or modify this barrier in pathological conditions such as brain tumors and brain stem cell carcinomas.
Topics: Animals; Biomarkers; Blood-Brain Barrier; Brain; Humans
PubMed: 34912450
DOI: 10.1155/2021/6564585 -
Chinese Medical Journal Oct 2016To systematically review the updated information about the gut microbiota-brain axis. (Review)
Review
OBJECTIVE
To systematically review the updated information about the gut microbiota-brain axis.
DATA SOURCES
All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of "gut microbiota", "gut-brain axis", and "neuroscience".
STUDY SELECTION
All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design.
RESULTS
It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota.
CONCLUSIONS
Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future.
Topics: Animals; Brain; Central Nervous System; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System
PubMed: 27647198
DOI: 10.4103/0366-6999.190667 -
Cell Aug 2015Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the... (Review)
Review
Advances in neuroscience identified addiction as a chronic brain disease with strong genetic, neurodevelopmental, and sociocultural components. We here discuss the circuit- and cell-level mechanisms of this condition and its co-option of pathways regulating reward, self-control, and affect. Drugs of abuse exert their initial reinforcing effects by triggering supraphysiologic surges of dopamine in the nucleus accumbens that activate the direct striatal pathway via D1 receptors and inhibit the indirect striato-cortical pathway via D2 receptors. Repeated drug administration triggers neuroplastic changes in glutamatergic inputs to the striatum and midbrain dopamine neurons, enhancing the brain's reactivity to drug cues, reducing the sensitivity to non-drug rewards, weakening self-regulation, and increasing the sensitivity to stressful stimuli and dysphoria. Drug-induced impairments are long lasting; thus, interventions designed to mitigate or even reverse them would be beneficial for the treatment of addiction.
Topics: Animals; Brain; Choice Behavior; Dopamine; Humans; Neural Pathways; Neuronal Plasticity; Reward; Substance-Related Disorders
PubMed: 26276628
DOI: 10.1016/j.cell.2015.07.046 -
Trends in Neurosciences Jul 2020The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the... (Review)
Review
The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the central nervous system (CNS). Imaging studies, as well as manipulations of fluid transport, point to a key role of the glymphatic-lymphatic system in clearance of amyloid-β and other proteins. As such, the glymphatic-lymphatic system represents a new target in combating neurodegenerative diseases. Not unexpectedly, introduction of a new plumbing system in the brain has stirred controversies. This opinion article will highlight what we know about the brain's fluid transport systems, where experimental data are lacking, and what is still debated.
Topics: Brain; Central Nervous System; Glymphatic System; Humans; Lymphatic Vessels; Neurodegenerative Diseases
PubMed: 32423764
DOI: 10.1016/j.tins.2020.04.003 -
Dialogues in Clinical Neuroscience Mar 2016Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and... (Review)
Review
Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and neurobiological studies. This work has given us a rich understanding of brain networks that promote habits, and has also helped us to understand what constitutes a habitual behavior as opposed to a behavior that is more flexible and prospective. Mounting evidence from studies using neural recording methods suggests that habit formation is not a simple process. We review this evidence and take the position that habits could be sculpted from multiple dissociable changes in neural activity. These changes occur across multiple brain regions and even within single brain regions. This strategy of classifying components of a habit based on different brain signals provides a potentially useful new way to conceive of disorders that involve overly fixed behaviors as arising from different potential dysfunctions within the brain's habit network.
Topics: Animals; Brain; Habits; Humans; Nerve Net
PubMed: 27069378
DOI: 10.31887/DCNS.2016.18.1/ksmith -
The Journal of Physiology Aug 2015Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural... (Review)
Review
Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.
Topics: Adolescent; Adolescent Development; Animals; Brain; Humans; Nicotine; Nicotinic Agonists
PubMed: 26018031
DOI: 10.1113/JP270492 -
Neuroscience and Biobehavioral Reviews Mar 2021The paper reviews the relations between sex and brain in light of the binary conceptualization of these relations and the challenges posed to it by the 'mosaic'... (Review)
Review
The paper reviews the relations between sex and brain in light of the binary conceptualization of these relations and the challenges posed to it by the 'mosaic' hypothesis. Recent formulations of the binary framework range from arguing that the typical male brain is different from the typical female brain to claiming that brains are typically male or female because brain structure can be used to predict the sex category (female/male) of the brain's owner. These formulations are challenged by evidence that sex effects on the brain may be opposite under different conditions, that human brains are comprised of mosaics of female-typical and male-typical features, and that sex category explains only a small part of the variability in human brain structure. These findings led to a new, non-binary, framework, according to which mosaic brains reside in a multi-dimensional space that cannot meaningfully be reduced to a male-female continuum or to a binary variable. This framework may also apply to sex-related variables and has implications for research.
Topics: Brain; Female; Humans; Magnetic Resonance Imaging; Male; Sex Factors
PubMed: 33440198
DOI: 10.1016/j.neubiorev.2020.11.018 -
International Journal of Molecular... Mar 2022The brain is one of the most energy-consuming organs in the body. Satisfying such energy demand requires compartmentalized, cell-specific metabolic processes, known to... (Review)
Review
The brain is one of the most energy-consuming organs in the body. Satisfying such energy demand requires compartmentalized, cell-specific metabolic processes, known to be complementary and intimately coupled. Thus, the brain relies on thoroughly orchestrated energy-obtaining agents, processes and molecular features, such as the neurovascular unit, the astrocyte-neuron metabolic coupling, and the cellular distribution of energy substrate transporters. Importantly, early features of the aging process are determined by the progressive perturbation of certain processes responsible for adequate brain energy supply, resulting in brain hypometabolism. These age-related brain energy alterations are further worsened during the prodromal stages of neurodegenerative diseases, namely Alzheimer's disease (AD), preceding the onset of clinical symptoms, and are anatomically and functionally associated with the loss of cognitive abilities. Here, we focus on concrete neuroenergetic features such as the brain's fueling by glucose and lactate, the transporters and vascular system guaranteeing its supply, and the metabolic interactions between astrocytes and neurons, and on its neurodegenerative-related disruption. We sought to review the principles underlying the metabolic dimension of healthy and AD brains, and suggest that the integration of these concepts in the preventive, diagnostic and treatment strategies for AD is key to improving the precision of these interventions.
Topics: Alzheimer Disease; Astrocytes; Brain; Humans; Neurons
PubMed: 35409145
DOI: 10.3390/ijms23073785