Advances in neurobiology最新文献

Auditory-verbal hallucinations (AVH) are debilitating symptoms experienced by those diagnosed with psychosis as well as many other neurological and psychiatric disorders. Critical to supporting individuals with AVH is identifying biomarkers that serve to track changes in brain states that put individuals at risk for developing or worsening of symptoms. There has been substantial literature identifying neural areas to track over time that may prove to be effective clinical tools. The efficacy of these tools has been bolstered when considering them under mechanistic accounts of AVH. In this chapter, we explore the literature that connects mechanistic theories and structurally based models of AVH and the potential biomarkers derived from this research.

Microglia have been implicated in numerous neurodegenerative and neuroinflammatory disorders; however, the causal contribution of this immune cell type is frequently debated. Genetic studies offer a unique vantage point in that they infer causality over a secondary consequence. Genome-wide association studies (GWASs) have identified hundreds of loci in the genome that are associated with susceptibility to neurodegenerative disorders. GWAS studies implicate microglia in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and to a lesser degree suggest a role for microglia in vascular dementia (VaD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and other neurodegenerative and neuropsychiatric disorders. The contribution and function of GWAS risk loci on disease progression is an ongoing field of study, in which large genomic datasets, and an extensive framework of computational tools, have proven to be crucial. Several GWAS risk loci are shared between disorders, pointing towards common pleiotropic mechanisms. In this chapter, we introduce key concepts in GWAS and post-GWAS interpretation of neurodegenerative disorders, with a focus on GWAS risk genes implicated in microglia, their interplay with other cell types and shared convergence of GWAS risk loci on microglia.

Multiple sclerosis (MS) is a devastating autoimmune disease that leads to profound disability. This disability arises from the stochastic, regional loss of myelin-the insulating sheath surrounding neurons-in the central nervous system (CNS). The demyelinated regions are dominated by the brain's resident macrophages: microglia. Microglia perform a variety of functions in MS and are thought to initiate and perpetuate demyelination through their interactions with peripheral immune cells that traffic into the brain. However, microglia are also likely essential for recruiting and promoting the differentiation of cells that can restore lost myelin in a process known as remyelination. Given these seemingly opposing functions, an overarching beneficial or detrimental role is yet to be ascribed to these immune cells. In this chapter, we will discuss microglia dynamics throughout the MS disease course and probe the apparent dichotomy of microglia as the drivers of both demyelination and remyelination.

Sleep is a physiological state that is essential for maintaining physical and mental health. Sleep disorders and sleep deprivation therefore have many adverse effects, including an increased risk of metabolic diseases and a decline in cognitive function that may be implicated in the long-term development of neurodegenerative diseases. There is increasing evidence that microglia, the resident immune cells of the central nervous system (CNS), are involved in regulating the sleep-wake cycle and the CNS response to sleep alteration and deprivation. In this chapter, we will discuss the involvement of microglia in various sleep disorders, including sleep-disordered breathing, insomnia, narcolepsy, myalgic encephalomyelitis/chronic fatigue syndrome, and idiopathic rapid-eye-movement sleep behavior disorder. We will also explore the impact of acute and chronic sleep deprivation on microglial functions. Moreover, we will look into the potential involvement of microglia in sleep disorders as a comorbidity to Alzheimer's disease and Parkinson's disease.

The temporal and spatial pattern of microglia colonization of the nervous system implies a role in early stages of organ development including cell proliferation, differentiation, and neurovascularization. As microglia colonize and establish within the developing nervous system, they assume a neural-specific identity and contribute to key developmental events. Their association around blood vessels implicates them in development of the vascular system or vice versa. A similar association has been reported for neural cell proliferation and associated phenotypic shifts and for cell fate differentiation to neuronal or glial phenotypes. These processes are accomplished by phagocytic activities, cell-cell contact relationships, and secretion of various factors. This chapter will present data currently available from studies evaluating the dynamic and interactive nature of these processes throughout the progression of nervous system development.

Astrocytes have gained increasing recognition as key elements of a broad array of nervous system functions. These include essential roles in synapse formation and elimination, synaptic modulation, maintenance of the blood-brain barrier, energetic support, and neural repair after injury or disease of the nervous system. Nevertheless, our understanding of mechanisms underlying astrocyte development and maturation remains far behind that of neurons and oligodendrocytes. Early efforts to understand astrocyte development focused primarily on their specification from embryonic progenitors and the molecular mechanisms driving the switch from neuron to glial production. Considerably, less is known about postnatal stages of astrocyte development, the period during which they are predominantly generated and mature. Notably, this period is coincident with synapse formation and the emergence of nascent neural circuits. Thus, a greater understanding of astrocyte development is likely to shed new light on the formation and maturation of synapses and circuits. Here, we highlight key foundational principles of embryonic and postnatal astrocyte development, focusing largely on what is known from rodent studies.

The first line of defense for the central nervous system (CNS) against injury or disease is provided by microglia. Microglia were long believed to stay in a dormant/resting state, reacting only to injury or disease. This view changed dramatically with the development of modern imaging techniques that allowed the study of microglial behavior in the intact brain over time, to reveal the dynamic nature of their responses. Over the past two decades, in vivo imaging using multiphoton microscopy has revealed numerous new functions of microglia in the developing, adult, aged, injured, and diseased CNS. As the most dynamic cells in the brain, microglia continuously contact all structures and cell types, such as glial and vascular cells, neuronal cell bodies, axons, dendrites, and dendritic spines, and are believed to play a central role in sculpting neuronal networks throughout life. Following trauma, or in neurodegenerative or neuroinflammatory diseases, microglial responses range from protective to harmful, underscoring the need to better understand their diverse roles and states in different pathological conditions. In this chapter, we introduce multiphoton microscopy and discuss recent advances in structural and functional imaging technologies that have expanded our toolbox to study microglial states and behaviors in new ways and depths. We also discuss relevant mouse models available for in vivo imaging studies of microglia and review how such studies are constantly refining our understanding of the multifaceted role of microglia in the healthy and diseased CNS.

Neuroimaging plays an important role in assessing the consequences of TBI across the postinjury period. While identifying alterations to the brain is important, associating those changes to functional, cognitive, and behavioral outcomes is an essential step to establishing the value of advanced neuroimaging for pediatric TBI. Here we highlight research that has revealed links between advanced neuroimaging and outcome after TBI and point to opportunities where neuroimaging could expand our ability to prognosticate and potentially uncover opportunities to intervene.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique able to depict the magnetic susceptibility produced by different substances, such as deoxyhemoglobin, calcium, and iron. The main application of SWI in clinical neuroimaging is detecting microbleedings and venous vasculature. Quantitative analyses of SWI have been developed over the last few years, aimed to offer new parameters, which could be used as neuroimaging biomarkers. Each technique has shown pros and cons, but no gold standard exists yet. The fractal dimension (FD) has been investigated as a novel potential objective parameter for monitoring intratumoral space-filling properties of SWI patterns. We showed that SWI patterns found in different tumors or different glioma grades can be represented by a gradient in the fractal dimension, thereby enabling each tumor to be assigned a specific SWI fingerprint. Such results were especially relevant in the differentiation of low-grade versus high-grade gliomas, as well as from high-grade gliomas versus lymphomas.Therefore, FD has been suggested as a potential image biomarker to analyze intrinsic neoplastic architecture in order to improve the differential diagnosis within clinical neuroimaging, determine appropriate therapy, and improve outcome in patients.These promising preliminary findings could be extended into the field of neurotraumatology, by means of the application of computational fractal-based analysis for the qualitative and quantitative imaging of microbleedings in traumatic brain injury patients. In consideration of some evidences showing that SWI signals are correlated with trauma clinical severity, FD might offer some objective prognostic biomarkers.In conclusion, fractal-based morphometrics of SWI could be further investigated to be used in a complementary way with other techniques, in order to form a holistic understanding of the temporal evolution of brain tumors and follow-up response to treatment, with several further applications in other fields, such as neurotraumatology and cerebrovascular neurosurgery as well.

Autism spectrum disorder is an increasingly prevalent and debilitating neurodevelopmental condition and an electroencephalogram (EEG) diagnostic challenge. Despite large amounts of electrophysiological research over many decades, an EEG biomarker for autism spectrum disorder (ASD) has not been found. We hypothesized that reductions in complex dynamical system behaviour in the human central nervous system as part of the macroscale neuronal function during cognitive processes might be detectable in whole EEG for higher-risk ASD adults. In three studies, we compared the medians of correlation dimension, largest Lyapunov exponent, Higuchi's fractal dimension, multiscale entropy, multifractal detrended fluctuation analysis and Kolmogorov complexity during resting, cognitive and social skill tasks in 20 EEG channels of 39 adults over a range of ASD risk. We found heterogeneous complexity distribution with clusters of hierarchical sequences pointing to potential cognitive processing differences, but no clear distinction based on ASD risk. We suggest that there is indication of statistically significant differences between complexity measures of brain states and tasks. Though replication of our studies is needed with a larger sample, we believe that our electrophysiological and analytic approach has potential as a biomarker for earlier ASD diagnosis.