Physical exercise is a potential medicine for cognitive function and mental health; however, regular exercise is more difficult than taking a pill every day. Developing an exercise environment that promotes a positive affective response to exercise and exercise benefits on the brain may encourage people to participate in physical activities. Listening to music while exercising is a promising candidate for such an "enriched exercise environment." This chapter reviews the studies demonstrating the beneficial effects of music on enhancing mood and cognitive function in both acute and chronic settings. Furthermore, the underlying neural mechanisms involved in the effects of exercise with music are discussed from the following three perspectives: (1) musical reward and pleasure, (2) rhythmic entrainment, and (3) sensory distraction. In addition, the concept of groove, which is "the pleasurable sensation of wanting to move the body to music" was used to explore the characteristics of music that are compatible with exercise. Finally, individual variations on whether combining exercises with music are appropriate and the considerations that should be addressed for implementation in the field are discussed.

This review aims to elucidate the positive effects of exercise on cognitive function and explore the underlying mechanisms. Extensive evidence supports the assertion that exercise positively influences neuroplasticity, learning and memory, and mitigates cognitive decline. Nevertheless, comprehending the intricate factors influencing the efficacy of exercise in cognitive improvement remains challenging. Further investigations are imperative to determine the optimal personalized exercise regimen, including the frequency, intensity, type, dosage, and duration, as a non-pharmacological, safe, and cost-effective approach to maximize cognitive benefits. This pursuit holds significant promise for advancing our understanding of exercise as a practical intervention to promote cognitive well-being.

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.

Alzheimer's disease (AD) is a common form of dementia characterized by cognitive decline and abnormal accumulation of proximate neurotoxins in older adults. It accounts for up to 80% of all dementia cases. AD is not exclusively attributed to aging; rather, it involves complex and multifactorial brain changes that can lead to severe functional dependence and ultimately death. Although there has been progress in the development of novel treatments for AD, they are yet to yield disease-modifying effects. Early detection and therapeutic interventions are critical for preventing or delaying the onset of AD. We aimed to provide an overview of emerging evidence on physical exercise as a therapeutic strategy for the prevention and treatment of AD. Studies have demonstrated the potential of exercise in improving cognitive function, reducing the risk of AD, and slowing disease progression by promoting various neuroplastic changes. Therefore, regular exercise should be considered as a disease-modifying intervention for AD and included in comprehensive treatment protocols. Further studies are warranted to establish the optimal exercise regimen for individuals with AD; nonetheless, incorporating exercise into daily routines may contribute toward the prevention and management of AD.

Multiple sclerosis (MS) is a chronic autoimmune and progressive neurodegenerative disease of the central nervous system (CNS) that has a highly variable clinical manifestation and course. MS targets primarily myelin and oligodendroglia; however, all glial cells and neurons become involved early in the pathology. Thus, inflammation, which is widely thought to be initiated peripherally, expands through the CNS, with astrocytes and microglia entering an activated state not only around and within lesions but also widespread. This chapter will emphasize the pathophysiological changes in oligodendrocytes and myelin as a consequence of the inflammatory cascade driving the disease onset and progression. Learning about the mechanisms of oligodendrocyte and myelin damage beyond the immune attack will be instrumental in protecting these two CNS compartments from damage. In turn, knowledge about the axon-myelin unit will help in devising therapies to prevent axonal degeneration, a key clinical hallmark of MS, as it strongly correlates with the progression of CNS atrophy and symptoms. Finally, exploiting paradigms of oligodendrocyte repopulation and remyelination will definitively contribute to devising treatments for tissue repair and halting MS course. This chapter aims at summarizing the state of the art in all these experimental developments including the available clinical therapies and the current clinical trials.

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.

The clinical efficacy of psychostimulant drugs, which target monoamine transporters, in treating attention-deficit/hyperactivity disorders (ADHDs) has stimulated interest on the role of transporter proteins like the dopamine(DA) transporter (DAT) in neurotransmission as well as the potential utility of DAT knockout organisms as models for neuropsychiatric disorders. Indeed, the study of DAT-deficient worms, flies, fish, mice, and rats has revealed a conserved role for DAT in the control of motor behavior as well as repetitive behavior, threat aversion, social behavior, and cognition in mammals. However, the disconnect between phenotypes observed in DAT-deficient model organisms and humans, which exhibit an early-onset syndrome characterized by Parkinsonism/dystonia and premature death, challenges the construct validity of DAT knockout models with respect to modeling neurobehavioral disorders. As an alternate approach, several groups have utilized coding variants in the SLC6A3 genelinked to psychiatric conditions, which display divergent molecular phenotypes. This chapter reviews the development and characterization of models of DAT gene deletion and mutation with a particular emphasis on comparing/contrasting the functional impact of DAT deficiency to DAT dysregulation triggered by neuropsychiatric disorder-linked DAT mutants in vivo. Ultimately, the study of DAT knockout and mutant models has revealed novel functions for DA in the mammalian brain, uncovered a dynamic interplay between the monoaminergic systems, highlighted sex differences in the DA system that determine the behavioral trajectory of DAT deregulation, and allowed for the screening of potential leads for therapeutics to treat disorders linked to aberrant dopaminergic neurotransmission.

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.

The dopamine transporter (DAT) is a plasma membrane protein expressed in dopamine (DA) neurons of the central nervous system and is critical for regulating DA neurotransmission. The DAT is responsible for the reuptake of released DA back into the presynaptic neuron, resulting in the termination of DA transmission. This process also recycles the DA back into the dopaminergic neuron for subsequent release. DAT is the target of psychostimulants including cocaine and amphetamines and has been associated with several neuropsychiatric disorders. Only DAT proteins located on the plasma membrane can remove DA from the extracellular space, and the number of DAT proteins on the cell-surface therefore determines the efficiency of DA clearance. As a result, regulating DAT surface expression is a critical means to regulating the magnitude and duration of DA neurotransmission. This chapter will discuss the different processes and proteins that have been shown to affect DAT surface expression and discuss the relevance to normal DA physiology and diseases that involve aberrant DA signaling.

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.