Advances in neurobiology最新文献

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.

Understanding exercise intensity is essential for optimizing training outcomes and minimizing health risks. This chapter introduces key physiological and subjective parameters used to assess exercise intensity, including heart rate reserve (HRR), oxygen uptake reserve (VO2R), maximal oxygen consumption (VO2max), and ratings of perceived exertion (RPE). Standardized classifications from organizations such as the American College of Sports Medicine (ACSM) are presented, alongside practical methods like the Talk Test for field applications. Incremental exercise testing is highlighted for identifying physiological thresholds, including lactate and ventilatory thresholds, which serve as critical markers for personalized training. Additionally, recent advances in neuroimaging-including electroencephalography (EEG), near-infrared spectroscopy (NIRS), and functional magnetic resonance imaging (fMRI)-are reviewed to explore how different exercise intensities affect brain activity. Evidence suggests that even low to moderate-intensity exercise can positively influence cognitive function and cerebral blood flow. The integration of wearable technologies has further enabled real-time monitoring of both physiological and neurocognitive responses. Overall, this chapter underscores the importance of individualized, evidence-based approaches in exercise prescription and highlights emerging methods for linking exercise intensity with brain function.

The dopamine transporter (DAT) plays a critical role in the central nervous system and has been implicated in numerous psychiatric disorders. The ligand-based approaches are instrumental to decipher the structure-activity relationship (SAR) of DAT ligands, especially the quantitative SAR (QSAR) modeling. By gathering and analyzing data from literature and databases, we systematically assemble a diverse range of ligands binding to DAT, aiming to discern the general features of DAT ligands and uncover the chemical space for potential novel DAT ligand scaffolds. The aggregation of DAT pharmacological activity data, particularly from databases like ChEMBL, provides a foundation for constructing robust QSAR models. The compilation and meticulous filtering of these data, establishing high-quality training data sets with specific divisions of pharmacological assays and data types, along with the application of QSAR modeling, prove to be a promising strategy for navigating the pertinent chemical space. Through a systematic comparison of DAT QSAR models using training data sets from various ChEMBL releases, we underscore the positive impact of enhanced data set quality and increased data set size on the predictive power of DAT QSAR models.

Oligodendroglia are the only cell lineage of the central nervous system (CNS) responsible for producing myelin. They originate from precursor cells known as oligodendrocyte precursor cells (OPCs), which are born around the ventricular zones of the brain and spinal cord and migrate throughout the developing CNS, and many of them ultimately differentiate into mature myelinating oligodendrocytes. Recent research has shown that OPCs and oligodendrocytes possess distinct characteristics when compared either to other types of glial cells in the CNS or to each other. Under different physiological and pathophysiological conditions, the processes of development or regeneration, the features, and, in some cases, even the functions of oligodendroglia can be modified. These changes can contribute to disease progression and affect the functional status of the nervous system. For instance, experience-dependent "adaptive" myelination plays a crucial role in the plasticity of neuronal circuits and influences learning processes; additionally, the non-myelinating functions of oligodendroglia expand their pathological potential, allowing them to regulate neuronal development and activity, angiogenesis, astrocyte maturation, and neuroinflammation. This chapter serves as a comprehensive introduction to oligodendroglia by presenting evidence from fundamental studies and fresh insights into their development, physiological and pathophysiological attributes, as well as the newly discovered non-myelinating functions.

Some neuronal populations in the brain have the ability to release multiple neurotransmitters, which may be packaged in the same vesicle, or released by distinct subsets of vesicles. Here, we review current knowledge on the molecular mechanisms by which multiple neurotransmitters can be stored in the same cell and the functional implications that this has for information processing throughout the brain and the control of movement execution by basal ganglia and cortical motor circuits.

Monoamine transmission is critical for regulating numerous physiological processes, including stress, learning, motor activity, and reward. Over the past few decades, the adoption of fast scan cyclic voltammetry has unveiled an intricate interplay between monoamine release and uptake dynamics, particularly concerning monoamine transporter involvement in reward and reinforcement processes for drugs of abuse. This review discusses how fast scan cyclic voltammetry has revolutionized our understanding of the processes that govern monoamine release and uptake, emphasizing the heterogeneity in transporter function across terminal regions, the influence of autoreceptors on monoamine transmission, and the complex interactions between drugs of abuse and monoamine transporters. While much of the review focuses on what is known about dopamine transporters-due to the wealth of evidence on dopamine transmission-we also emphasize significant gaps in knowledge regarding the serotonin and norepinephrine transporters. Finally, we highlight remaining questions about the dynamic nature of monoaminergic transporter efficiency and suggest new areas of investigation to gain a more comprehensive understanding of the biochemical mechanisms through which monoamine transporters regulate behavior.

Cognitive dysfunction in type 2 diabetes mellitus (T2DM) poses a significant peril not only to compromised human well-being but also to the onset of dementia, Alzheimer's disease, and depression. Given the present research findings utilizing animal models, various potential biochemical mechanisms have been reported for hippocampus-based cognitive dysfunction in T2DM. This chapter focuses on the relationship between cognitive dysfunction in T2DM and dysregulation of the hippocampal astrocyte-neuron lactate shuttle, with specific emphasis on monocarboxylate transporter 2 (MCT2). Furthermore, it provides a summary of the evidence suggesting the potentiality of exercise as a viable therapeutic intervention, encompassing not solely glycemic control but also the amelioration of cognitive dysfunction in T2DM.

Monoamine transporters are essential proteins located at presynaptic terminals that play a crucial role in regulating neurotransmission of serotonin, dopamine, and norepinephrine by rapid reuptake of released amines from the synapse. Clinically used antidepressants and widely abused psychostimulants exhibit a high affinity for amine transporters. Function and expression of biogenic amine transporter are altered in subjects suffering from psychiatric diseases such as depression and in psychostimulant use disorder. Therefore, proper functional regulation of monoamine transporters is critical in maintaining normal amine homeostasis. Monoamine transporters possess several potential phosphorylation sites/motifs and exist in a phosphorylated state. Various cellular protein kinases and phosphatases are known to regulate the phosphorylation dynamics of amine transporters, which in turn influences subcellular expression and trafficking, microdomain-specific protein-protein interactions, transporter protein degradation, and overall transport capacity. Dysfunctional amine transporter function, phosphorylation, and association with interacting proteins are evident in neuropsychiatric disease states, including psychostimulant use disorder. However, the neurobiological consequences of in vivo amine transporter phosphorylation and its regulation remain unclear. Recent studies utilizing intact animal models are beginning to connect these molecular mechanisms with observed animal behaviors. This review summarizes current knowledge on the causal role of amine transporter phosphorylation in regulating amine transport and its relevance to animal behavior. Further understanding of phosphorylation-dependent molecular mechanisms governing amine transporter regulation potentially identifies regulatory motif(s) as potential therapeutic targets for treating neuropsychiatric disorders.

Dopamine (DA) is an important modulatory neurotransmitter that is involved in daily activities such as movement, memory, and reward-oriented learning of essential behaviors and needs. DA signaling is initiated by the release of DA into the synaptic cleft that will bind to dopamine receptors to mediate the physiological response. To terminate the DA response, the DA is taken up by the dopamine transporter (DAT), a surface membrane protein. Psychostimulants, like cocaine and amphetamine, both target DAT and interfere with the DA uptake process, resulting in an increased amount of DA in the synaptic cleft. Continuous use of psychostimulants can lead to psychostimulant use disorders (PUDs), which are marked by uncontrollable psychostimulant craving and misuse. Because of the unmet need for treatment options for PUDs, novel strategies for discovering therapies are essential. Over the years, DAT-targeting ligands have been identified with atypical properties such as reduced abuse liability compared to cocaine. These compounds have been proposed to bind to different sites from cocaine and/or prefer and stabilize specific conformations of DAT. In addition, some of these compounds can interfere with psychostimulant-DAT binding and may have therapeutic potential in treating PUDs. This chapter introduces the role of DAT in PUDs, presents the mechanism of action of novel DAT-binding ligands, and discusses the therapeutic potential of atypical DAT-binding ligands for PUDs.

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.