Advances in neurobiology最新文献

Adult hippocampal neurogenesis (AHN) is the process of generating new neurons in the adult hippocampal dentate gyrus (DG). Exercise promotes AHN and improves hippocampal function through neuroplastic enhancement. The underlying regulatory factors of this process are currently being vigorously studied. However, many previous studies have used a rodent wheel-running model, in which the exercise condition (e.g., volume, intensity, duration) cannot be controlled. In contrast, treadmill running (TR) allows the precise regulation of conditions such that animals can run according to specific experimental aims. Understanding the intensity-dependent effects of exercise on AHN and hippocampal functions, and the underlying mechanisms, is crucial for the development of exercise prescriptions for humans in diverse educational and clinical fields. Based on the lactate threshold (LT), an inflection point at which blood lactate accumulation drastically rises during incremental exercise, exercise can be defined as minimal-stress light-intensity exercise (below LT) and exercise-derived-stress vigorous-intensity exercise (above LT). This chapter begins with a brief overview of AHN, followed by a discussion of LT-based exercise effects on AHN and hippocampal function as they vary with exercise intensity, primarily following the findings from the TR models, and closing with the molecular factors involved in AHN and hippocampal function regulation.

It has been suggested that acute physical exercise at low to moderate intensity improves cognitive function, as shown by improvements in cognitive performance. Decades of research have explored or discussed physiological mechanisms underlying cognitive improvements induced by acute exercise. However, the precise physiological mechanisms responsible for improvements in cognitive function remain to be elucidated. There is a large body of evidence to suggest that cognitive function is linked with dopamine (DA) in the brain. Rodent studies have shown that acute exercise releases neurotransmitters in the brain. Recent studies using positron emission tomography (PET) have also suggested that acute exercise released endogenous DA in humans. Furthermore, it appears that endogenous DA release is linked with improvements in cognitive function induced by acute exercise. Therefore, in this chapter, we focus on DA and discuss it as a promising candidate to account for exercise-cognition interaction, particularly improvement in cognitive function induced by acute exercise. We propose that further studies using PET would be helpful to progress our understanding of improvements in cognitive function induced by acute exercise.

Drosophila melanogaster, commonly referred to as the "fruit fly," has been a long-utilized animal model in multiple areas of biological research. It is estimated that 75% of human genes, which are associated with disease, have homologues in Drosophila. The conservation of biological systems, the genetic tractability, short generation time, and a broad array of available behavioral assessments make Drosophila an especially robust model organism for neuroscience investigations. The dopamine (DA) system, in particular, is highly conserved between mammals and Drosophila. Mutations of the DA transporter (DAT), a negative regulator of DA neurotransmission, have been associated with multiple different neuropsychiatric and neurodegenerative disorders, including autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), and Parkinson's disease (PD). Utilization of Drosophila models demonstrates specific structural and functional alterations in mutated DAT that manifest as unique behavioral phenotypes. Ultimately, combining techniques ranging from biochemistry, electrochemistry, and complex behavioral analyses facilitated a deeper understanding of how transporter function and dysfunction can translate to neurological and neuropsychiatric disorders.

The evolution of the nervous system emerged in primaeval animals to coordinate their behaviour then advanced by the division of function between neurones and neuroglia; neurones became dedicated to information processing and neuroglia specialised in homeostatic support. As the nervous system became more complex and neurones extended axonal connections, so periaxonal glial cells arose to provide axonal support. In many invertebrates, periaxonal glia produce multilamellar structures similar in architecture and function to the myelin sheath of vertebrates. These protomyelin structures support exceptionally high velocity of action potential propagation, which in some shrimps may reach 200 m/s. Myelin sheaths 'proper' are a vertebrate development and emerged in jawed fish with the central nervous system (CNS) of the brain and spinal cord becoming enclosed within the cranium and vertebral column. This was coincident with a clear division between oligodendrocytes that myelinate axons in the CNS and Schwann cells that myelinate peripheral axons; it seems likely that peripheral myelin evolved first. In the CNS, myelinated axons form the white matter, which interconnects the different regions of the CNS with each other and with the periphery. This is termed the connectome, which is particularly advanced in humans, occupying ~50% of total volume of the brain, compared to ~12% in rodents. The highly developed connectome, supported by oligodendroglial cells, is the foundation of human intelligence.

Myelinating oligodendrocytes and oligodendrocyte precursor cells (OPCs) make up half the cells in the central nervous system and are affected by and contribute to all neurological diseases. The pathology of myelinating oligodendrocytes is fundamentally characterized by myelin disruption and loss, termed demyelination, whereas that of OPCs is principally defined by remyelination and repair in the form of regeneration of myelinating oligodendrocytes. Demyelination is generally associated with white matter diseases, such as multiple sclerosis, although oligodendroglial pathology is a major factor in most neuropathologies, including Alzheimer's disease, ischaemic injury, and traumatic injury. Oligodendroglial changes are often driven by neuroinflammatory factors and involve oxidative stress, metabolic malfunction, and excitotoxicity. Understanding the complexities of demyelination and remyelination pathogenesis is essential for the development of new therapeutic strategies. In this chapter, we summarise the key features of demyelination and remyelination, discuss factors underlying a remyelination failure, and compare the differences between humans and mice. We propose some perspectives on treatment strategies for remyelination in the hope that future advances will provide solutions to the challenges associated with demyelinating diseases.

This chapter delves into the impact of acute exercise on executive function-a key component of cognitive functions. Despite a robust body of evidence showcasing the substantial benefits of chronic exercise on executive function, a notable gap exists in our understanding of its acute effects. The chapter unfolds in four key segments. Firstly, it provides a succinct definition of executive function. Subsequently, it synthesizes findings from previous systematic reviews and meta-analyses, elucidating the overall impact of acute exercise on executive function. Despite occasional discrepancies in individual studies, a consistent positive association emerges. The third segment employs the 3W+1H framework to explore moderators shaping this relationship, scrutinizing the "Who, What, When, and How" factors. Through this lens, the chapter aims to uncover nuanced conditions under which acute exercise optimally enhances executive function. Lastly, the chapter outlines future research directions, emphasizing the necessity for targeted investigations to refine our understanding of the intricate interplay between acute exercise and executive function. This inquiry contributes to the ongoing discourse on the benefits of exercise for executive function, offering insights with potential applications in both research and practical contexts to promote cognitive well-being.

Aerobic exercise works as a "brain stimulation" or "medicine" to improve executive function, memory, and mental health. In addition to this evidence, recent studies have demonstrated that aerobic exercise positively affects neuroplasticity in the sensorimotor cortex, which is essential for motor skill learning, or rehabilitation in patients with central nervous system disorders. A shift in the excitatory/inhibitory balance within the sensorimotor cortex through the modulation of intracortical excitability elicited by aerobic exercise has been postulated as the underlying mechanism. In this chapter, we focus on acute aerobic exercise and summarize the effects of aerobic exercise on neuroplasticity in the sensorimotor cortex. Additionally, we describe the effects of acute aerobic exercise on changes in intracortical excitability and shifts in excitatory/inhibitory balance, which are considered mechanisms of enhanced neuroplasticity, with a brief explanation of the methods used to evaluate them. We provide important insights into the potential benefits of exercise beyond cognition and memory, thus expanding the role of aerobic exercise as a "brain stimulation" and "medicine."

Oligodendrocytes are cells in the central nervous system that are specialised to form myelin sheaths around axons. They are generated from oligodendrocyte precursor cells that persist in the adult brain and are responsible for myelin plasticity that is essential for learning and repair in pathology. Oligodendrocytes exhibit morphological and molecular heterogeneity, and, besides their role in myelination, they provide metabolic and homeostatic support for neurones. In addition, some oligodendrocytes exhibit an immune function as antigen-presenting cells under certain conditions. The myelinating function of oligodendrocytes is essential for nervous system operational integrity, and the loss of myelin leads to neurodegeneration and an irreversible loss of function.

This chapter provides a comprehensive review of white matter injuries, with a particular focus on oligodendrocyte lineage cell-mediated mechanisms and strategies. Traumatic mechanical insults, vascular conditions, perinatal injuries, and degenerative diseases all have white matter components and can be studied using different animal models. These distinct etiologies converge on similar pathophysiological features comprised of programmed cell death of oligodendrocyte lineage cells, demyelination, release of myelin debris, ion imbalance, excitotoxicity, mitochondrial dysfunction, and Wallerian degeneration. Therapeutics that target oligodendrocyte lineage cells are warranted due to their role in remyelination, immunomodulation, circuit remodeling, and maintenance of vasculature. Thus, emerging diagnostic techniques can help in assessing the extent of oligodendrocyte lineage cell-related pathology, while regenerative treatments, including cell transplantation, endogenous cell mobilization, biomaterials, and rehabilitation, can facilitate recovery by driving regeneration of oligodendrocyte lineage cells and myelin. Despite tremendous progress in this field, the heterogeneity of oligodendrocyte lineage cells suggests that a personalized medicine approach may optimize recovery following injury.

Solute carrier 6 family members comprise of neurotransmitter sodium symporters that are the transporters primarily involved in the reuptake of released neurotransmitters from the synaptic space. The family includes structurally related transporters involved in biogenic amine and amino acid neurotransmitter uptake and is a well-known therapeutic target for several classes of inhibitors for the treatment of ailments ranging from depression, pain, addiction, seizures and anxiety. Inhibition of NSS transporters can work either through competitive inhibition or through allosteric inhibition at diverse sites that target multiple conformational states of the transporters. This chapter explores the diverse inhibition strategies observed with numerous inhibitors that target this class of transporters and potential for improvements in inhibition strategies.