International review of neurobiology最新文献

Amyotrophic lateral sclerosis (ALS) is a neurological disease marked by the degeneration of motor neurons, leading to muscle weakness and paralysis. While the cause of ALS is uncertain, research indicates that changes in the gut microbiome may influence the disease's progression. This chapter explores how alterations in gut microbiota affect the enteric neuromuscular system (ENS) in ALS. In ALS patients, disrupted gut microbiota are linked to the brain-gut axis, impacting both gastrointestinal function and neuronal health. Studies show that microbial changes are associated with inflammation, immune instability, and neurodegeneration, which exacerbate the disease. Gastrointestinal issues like constipation and dysphagia in ALS are tied to ENS dysregulation. Understanding the connections between the gut microbiome, ENS, and central nervous system (CNS) may lead to novel therapies targeting neurodegeneration and microbial dysbiosis in ALS.

Changes in the makeup of gut microbiota are linked to many neuropsychiatric diseases. Although the exact connection between gut dysbiosis and brain dysfunction is not yet fully understood, but recent data suggests that gut dysbiosis may contribute to the development of Alzheimer's disease (AD) by promoting neuroinflammation, insulin resistance, oxidative stress, and amyloid-beta (Aβ) aggregation. Gut dysbiosis in animal models is primarily characterized by an elevated ratio of Firmicutes/Bacteroidetes which may lead to the accumulation of amyloid precursor protein (APP) in the intestine, in the early stages of AD. Probiotics play a significant role in preventing against the symptoms of AD by restoring gut-brain homeostasis. This chapter provides an overview of the gut microbiota and its dysregulation in etiology of AD. Moreover, novel insights into alteration of the composition of gut microbiota as a preventive or therapeutic approach to AD are discussed.

MG epidemiology may provide clues to disease etiology and pathogenesis. It is crucial for health planning and to estimate societal needs for health care resources. Recent high-quality studies have found an annual MG incidence of approximately 20 per million person-years, and a prevalence of approximately 25 per 100,000 population. Geographical variation reflects differences in case finding and diagnostic tools, but also a multitude of genetic and environmental etiological and risk factors. MG prevalence has increased in recent years because of more elderly people in the general population, improved case finding, and improved MG treatment with reduced mortality. In populations with optimal treatment, there is only a slightly increased mortality risk with MG. There are marked variations among MG disease subgroups regarding epidemiology. MuSK MG is more common in the Mediterranean area, juvenile MG is most common in China, whereas late onset MG with AChR antibodies is a subtype that has increased in incidence and prevalence globally.

Myasthenia gravis (MG) is the prototypical disorder of the neuromuscular junction. The clinical hallmarks of MG are fatigability and fluctuating voluntary muscle weakness. Although MG can potentially affect any muscle, some muscle groups are involved preferentially and an important clinical distinction can be made between the disease localized exclusively to the extraocular muscles and the disease affecting other muscle groups, called "generalized", with relevant therapeutic and prognostic implications. The clinician should be familiar with both common and uncommon patterns of weakness associated with MG and actively search for suggestive anamnestic cues when this disease is suspected. This chapter will focus on the different clinical presentations of MG, encompassing both the detailed clinical complaints and the anamnestic aspects, with a focus on the specific muscular distribution, and the clinical features associated with myasthenic crisis. Lastly, the most described atypical presentations and their differential diagnostic work-up will be reviewed.

Advances in immunology over the last several years have provided insights into the pathophysiology of autoimmune diseases such as generalized myasthenia gravis (gMG). This has translated into the development of effective, rapidly acting, and targeted novel immune therapies. The two categories of new therapies available at present include the complement C5 inhibitors and the neonatal Fc receptor (FcRn) antagonists. The place of these drugs in the algorithm of MG treatment continues to evolve. Simultaneously, drug development proceeds, with other complement inhibitors, new B cell inhibitor therapy, chimeric antigen therapies and immune tolerizing therapies are in the pipeline. The treatment of gMG will continue to evolve; treatments for subgroups of patients including MuSK- ab+, seronegative and thymoma-associated MG are important areas for future development.

Sleep is vital for physical and mental health and plays an important role in general well-being. Given the high prevalence of sleep disturbances in contemporary society, developing effective sleep-enhancing interventions, including non-pharmacological approaches such as hypnosis, is important. In this chapter, we will first discuss the nature of sleep and the factors that can disturb it. We will present scientific evidence on how hypnotherapy can improve sleep parameters and disturbances. This will be followed by the presentation of experimental studies highlighting the potential of hypnotic suggestions to modulate objective parameters of sleep depth. In conclusion, we will hypothesise on a potential mechanism by which hypnotic suggestions might be capable of modulating sleep.

Placebo effects refer to changes in outcomes driven by learning and expectations, and they can shape responses to both pharmacologic and non-pharmacologic interventions. This chapter examines the neurobiology of placebo and nocebo effects, with an emphasis on findings from human research. Drawing primarily from controlled laboratory studies, we highlight neuroimaging and transcriptomic mechanisms that shed light on the formation of placebo and nocebo responses. In particular, this chapter highlights how expectations and contextual cues can enhance or diminish the efficacy of both pharmacologic and non-pharmacologic interventions. A focus is placed on the role of open-label, cost perception, branding, and treatment modality in modulating placebo effects. The neurochemical basis of placebo analgesia is also examined, with a central role identified for endogenous opioids, and additional contributions from the endocannabinoid and dopaminergic systems. Neuroimaging studies reveal brain networks and structural markers that predict placebo responsiveness. Genetic and transcriptomic insights add a molecular layer to this understanding as well as RNA expression profiles, helping to identify placebo responders. Finally, the chapter emphasizes the clinical relevance of nocebo effects, detailing how negative expectations and communication can worsen outcomes. We also discuss the clinical relevance of these mechanisms, particularly in rheumatology, where both functional and structural brain changes have been observed. It advocates for improved communication strategies, personalized consent, and ethical integration of placebo science to optimize pain care and clinical trial designs. Future research should focus on translating individual variability in placebo and nocebo effects into strategies for advancing personalized and precision medicine.

Animal models offer a platform to advance our understanding of myasthenia gravis (MG), an autoimmune disorder characterized by impaired neuromuscular transmission. Experimental autoimmune MG models (EAMG) actively induce autoimmunity through antigen immunization, aiding in understanding the immune response to self. Passive transfer models (PTMG) involve the injection of pathogenic antibodies into animals, providing insights into antibody-mediated mechanisms and complement-driven damage to the neuromuscular junction (NMJ). The pathogenic effect of autoantibodies targeting acetylcholine receptors (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4) results in changes to the NMJ that are mechanistically distinct. These models validate therapeutic interventions preclinically, with methodologies ranging from antibody transfer to genetic modifications. Despite the translational challenges, these models bridge preclinical research and clinical applications, enabling the development of targeted treatments for MG.

Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies attack proteins at the neuromuscular junction, resulting in impaired neuromuscular transmission. Like other autoimmune diseases, MG arises when the immune system fails to distinguish self from non-self, attacking and damaging normal tissues. The pathological response involves not only B cells, responsible for autoantibody production, but also T cells, which provide essential support for B cell pathogenicity. While the precise triggers of this abnormal immune response remain undefined, MG is recognized as a multifactorial disease influenced by immune dysregulation along with genetic and environmental factors. This chapter explores the complex immunopathology of MG, highlighting how these factors collectively contribute to disease development. We examine the physiological development of T and B cell compartments, the tolerance checkpoints designed to prevent autoimmunity, and the consequences of their failure. Finally, we discuss the dysregulation of these cellular compartments in MG, emphasizing their roles in disease progression, the persistence of autoimmunity, and responses to treatment.