Advances in neurobiology最新文献

The importance of physical activity in neuroscience is gaining increasing recognition. The question arises: What is the specific focus of exercise, and what factors contribute to the observed benefits of exercise in neuroscience? Various forms of exercise have been examined across physiological, psychological, and biochemical experiments within neuroscience. Still, there is a need for greater clarity to identify optimal exercise conditions, including the FITT-VP variables (frequency, intensity, type, and time).This chapter aims to shed light on the positive impacts of high-intensity training (HIT) exercises in facilitating physiological adaptation and exploring the newfound role in brain functions. Key areas explored include (1) exercise neuroscience at the structural level involving synaptic plasticity and neurogenesis; (2) functional level concerning behavioral development; and (3) molecular level addressing potential mechanisms underlying exercise-induced brain plasticity.Overall, high-intensity training emerges as a more cost-effective method for enhancing physiological adaptations, including improvements in aerobic capacity. Additionally, it has been shown to influence brain functions such as hippocampus-dependent learning and memory positively. These findings offer valuable insights into the practicality of high-intensity training for performance improvement and suggest directions for future research.

Exercise has a remarkable capacity to improve brain function by fostering neuronal plasticity, which enables us to better cope with various psychological and cognitive challenges. Numerous studies have demonstrated the neuroprotective effects of exercise. However, the underlying molecular mechanisms of the neuroprotective effects of exercise are not yet fully understood. In particular, the role of exercise-induced secretion of peripheral factors into circulation that influence the brain is understudied. Recent research has shown that extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are secreted during exercise. The discovery that EVs can mediate intracellular communication by delivering cargo signifies a promising area of research to understand the impact of exercise on the brain. In the present review, we provide an overview of recent advancements in understanding the regulatory mechanisms of EV biogenesis and discuss how EV molecular composition is influenced by exercise. Additionally, we highlight the potential role of EVs as exercise-specific mediators and as a promising therapeutic tool for neurodegenerative diseases, such as Alzheimer's disease.

The central nervous system is susceptible to gradual decline with age, affecting all types of glial cells in the process. Compared to other glial cells, the oligodendroglial lineage is highly vulnerable to ageing and undergoes significant characteristic changes that impact upon its structure and impair its physiological functions. Therefore, the ageing and degeneration of oligodendroglia become major risk factors for neurodegenerative diseases. During the age-related disease process, changes in oligodendroglia lead to a decline in their ability to regenerate myelin and respond to the aged microenvironment, which are closely linked to the pathogenesis of neurodegenerative diseases, facilitating the emergence of these diseases in older populations. In this chapter, we introduce the physiological changes of oligodendroglia during ageing and the related mechanisms and then summarise their pathophysiological contributions to age-related cognitive disorders. Finally, we discuss potential therapeutic strategies that target oligodendroglia for future research on neurodegenerative diseases.

Myelin sheaths formed by oligodendrocytes (OLs) wrap around neuronal axons and allow for saltatory conduction of nerve impulses, significantly increasing the speed of electrical signal transmission. The development of oligodendrocyte lineage consists of several coordinated steps. Briefly, oligodendrocyte precursor cells (OPCs) are first generated from neural precursor cells of certain neuroepithelial regions, and then they proliferate and migrate to other regions of the central nervous system (CNS), where they differentiate into oligodendrocytes and form myelin sheaths around the axons of neurons. These developmental processes are tightly and precisely regulated during animal development by a cohort of intracellular molecular and extracellular signals.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system, in which aquaporin-4 immunoglobulin G (AQP4-IgG) targets the water channel aquaporin-4 (AQP4) localized at astrocytic endfeet, thus triggering inflammatory lesions and tissue damage. The pathological characteristics of NMOSD are early loss of oligodendrocytes, extensive demyelination, and axonal injury. The pathogenesis of oligodendrocyte damage in NMOSD includes complement-dependent bystander effect, antibody-dependent cell-mediated cytotoxicity bystander effect, glutamate toxicity, connexin dysregulation, and blood-brain barrier disruption. Remyelination levels in acute NMOSD lesions are low.

In this chapter we will show how electrophysiological recordings were used to gain insights into the transport kinetics and pharmacology of monoamine transporters (MATs). We will discuss data obtained from whole cell patch clamp recordings that allow for real time monitoring of MAT function. A notable property of MATs is that they carry so-called uncoupled currents. We will begin this chapter by reviewing the experimental evidence that has led to the conclusion that the currents carried by MATs are largely uncoupled and, therefore, not directly related to substrate transport. We will discuss how this has made it difficult to understand the operation of MATs. We will also explain why the existence of these currents has led to the proposition that MATs do not operate by alternate access but rather by a single file diffusion mechanism. However, we will show that ultimately the uncoupled currents carried by MATs can be most parsimoniously explained within the framework of the alternate access mechanism. We will review the existing evidence that MATs, like most other transporters, undergo a cycle during which they visit outward and inward-facing conformations (i.e., the transport cycle). We will outline what we have learned about the transport cycle of MATs from electrophysiological recordings. Thereafter, we will describe how electrophysiological recordings can be utilized to understand how drugs that target MATs affect their operation. To this end, we will discuss the binding modes of three different MAT ligands: (i) amphetamines, (ii) ibogaine, and (iii) zinc.

Proper physical activity, even at a very light intensity such as walking or slow running, improves brain health related to prefrontal executive function and hippocampal memory. However, the neural mechanism behind the cognitive enhancement that occurs during dynamic aerobic exercise is elusive and remains unclear in humans. Recently, pupillometry has been attracting attention as a kind of readout of the brain's ascending arousal mechanism, especially for brain noradrenergic and cholinergic system activation. Thus, to identify the neural mechanism behind the effects of very-light-intensity exercise, our recent work has focused on pupillometry during aerobic exercise, and we have successfully shown the efficacy of pupil dilation as a biological marker, even during very-light-/light-intensity exercise (below the ventilatory threshold). Interestingly, neuromelanin-MRI contrast in the LC, a marker of LC integrity, predicted the magnitude of exercise-induced pupil dilation and psychological arousal changes at the individual level. In addition, we have found that pupil dilation during exercise predicted the positive impact of acute very-light-/light-intensity exercise on prefrontal executive performance and hippocampal memory performance. The series of exercise pupillometry studies we will discuss here provides essential insights into the neural substrates of the advantages of exercise-induced brain stimulation in humans.

Physical activity has been proven to be beneficial for brain function. Due to a lack of appropriate therapies for the majority of brain diseases, exercise has become a favored alternative to prevent and even treat several of these pathologies. Thus, the mechanisms underlying the neuroprotective actions of exercise are under intense scrutiny. Furthermore, since many patients afflicted with different neurological conditions are not able to perform exercise, development of pharmacological mimics based on knowledge of underlying cellular and molecular mechanisms is of therapeutic interest (Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Cell 134:405-415, 2008). As part of these mechanisms, we will examine the role of insulin-like growth factor I (IGF-I), a pleiotropic neuroprotective signal, and one of the established mediators of the beneficial actions of exercise in the brain. Exercise stimulates the entrance of circulating IGF-I into the brain where it mediates pro-neurogenic, pro-cognitive, and mood modulatory effects known to be associated to exercise. Through its potent cytoprotective actions (anti-apoptotic, anti-oxidant, anti-inflammatory), IGF-I participates in reparative and homeostatic processes associated to exercise. We postulate that circulating IGF-I, a regulator of muscle and bone mass, forms part of an interoceptive system within a humoral branch informing the brain of muscle/bone mass. In this way, IGF-I conveys interoceptive signaling to brain areas involved in orchestrating physical activity to adapt them to available vigor, i.e., muscle strength. Because exercise engages the activity of many brain areas, neuroprotection by exercise-elicited entrance of circulating IGF-I is brain-wide.

Oxidative stress in the brain is associated with the development and progression of neurological disorders, posing antioxidant nutrients as an effective strategy for protecting neuronal cells and potentially slowing cognitive decline. Bioactive compounds from natural sources with antioxidant effects promote brain health. Among various natural compounds, astaxanthin (ASX), a potent red-pigment carotenoid found in various microorganisms and marine animals, is well recognized for its potential health benefits. In this review, we highlight the promising neuroprotective effects of ASX through cellular experiments and animal models. This review can provide novel insights on the therapeutic potential of ASX through its antioxidant, anti-inflammatory, and anti-apoptotic effects against neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In addition to demonstrating the neurotrophic effects of ASX on structural and functional changes in hippocampal neuronal plasticity, this review also discusses its synergistic potential with other interventions, such as exercise.

While moderate exercise has been demonstrated to enhance executive function, this beneficial effect may vary depending on the exercise environment. For instance, the decline in blood oxygen levels (hypoxemia) associated with ascent to high altitude has been shown not only to induce acute mountain sickness but also to potentially cause decreased cognitive performance. Therefore, exercise under hypoxic conditions may reduce oxygen delivery to various tissues, thereby attenuating the executive function-enhancing effects of exercise. Previous studies have examined the impact of exercise in hypoxic environments on cognitive function using cognitive task paradigms; however, a consensus has not been reached. One contributing factor to this lack of consensus is the insufficient investigation of how exercise in hypoxic environments affects neural activity in brain regions specific to cognitive function tasks. This limitation stems from the practical difficulties of utilizing positron emission tomography (PET) and magnetic resonance imaging (MRI) systems in hypoxic environments. We addressed these challenges by employing functional near-infrared spectroscopy (fNIRS), which requires only a compact experimental system, is portable, and can be readily installed in gym settings. Our findings revealed that exercise in hypoxic environments induces decreasing cognitive performance, specifically cognitive fatigue, by reducing task-specific neural activity. This chapter provides an overview of our research methodology and results.