Advances in neurobiology最新文献

Advances in molecular biology and genetics are increasingly revealing the complex etiology of autism spectrum disorder (ASD). In parallel, a number of biochemical, anatomical, and electrophysiological measures are emerging as potential disease-relevant biomarkers that could inform the diagnosis and clinical management of ASD. Rodent ASD models play a key role in ASD research as essential experimental tools. Nevertheless, there are challenges and limitations to the validity and translational value of rodent models, including genetic relevance and cognitive performance differences between humans and rodents. In this chapter, we begin with a brief history of autism research, followed by prominent examples of disease-relevant mouse models enabled by current knowledge of genetics, molecular biology, and bioinformatics. These ASD-associated rodent models enable quantifiable biomarker development. Finally, we discuss the prospects of ASD biomarker development.

Since the early 1990s, there have literally been thousands of reports related to magnetic resonance imaging of the autistic brain. The goals of these studies have ranged from identifying the earliest biological predictors of an autistic diagnosis to determining brain systems most altered in autistic individuals. Some of the later works attempt to use distinct patterns of brain alterations to help define more homogenous subtypes of autism. Far less work has been done to identify brain changes that are associated with therapeutic interventions. In this chapter, we will touch on all of these efforts as they relate to the general topic of the usefulness of brain imaging as a biomarker of autism.

Systems neuroscience explores the intricate organization and dynamic function of neural circuits and networks within the brain. By elucidating how these complex networks integrate to execute mental operations, this field aims to deepen our understanding of the biological basis of cognition, behavior, and consciousness. In this chapter, we outline the promising future of systems neuroscience, highlighting the emerging opportunities afforded by powerful technological innovations and their applications. Cutting-edge tools such as awake functional MRI, ultrahigh field strength neuroimaging, functional ultrasound imaging, and optoacoustic techniques have revolutionized the field, enabling unprecedented observation and analysis of brain activity. The insights gleaned from these advanced methodologies have empowered the development of a suite of exciting applications across diverse domains. These include brain-machine interfaces (BMIs) for neural prosthetics, cognitive enhancement therapies, personalized mental health interventions, and precision medicine approaches. As our comprehension of neural systems continues to grow, it is envisioned that these and related applications will become increasingly refined and impactful in improving human health and well-being.

Besides its two defining misfolded proteinopathies-Aβ plaques and tau neurofibrillary tangles-Alzheimer's disease (AD) is an exemplar of a neurodegenerative disease with prominent reactive astrogliosis, defined as the set of morphological, molecular, and functional changes that astrocytes suffer as the result of a toxic exposure. Reactive astrocytes can be observed in the vicinity of plaques and tangles, and the relationship between astrocytes and these AD neuropathological lesions is bidirectional so that each AD neuropathological hallmark causes specific changes in astrocytes, and astrocytes modulate the severity of each neuropathological feature in a specific manner. Here, we will review both how astrocytes change as a result of their chronic exposure to AD neuropathology and how those astrocytic changes impact each AD neuropathological feature. We will emphasize the repercussions that AD-associated reactive astrogliosis has for the astrocyte-neuron interaction and highlight areas of uncertainty and priorities for future research.

Proper functioning of the central nervous system depends on various tightly regulated phenomena, among which astrocyte-neuron interactions are of critical importance. Various studies across the species have highlighted the diverse yet crucial roles of astrocytes in regulating the nervous system development and functions. In simpler organisms like worms or insects, astrocyte-like cells govern basic functions such as structural support to neurons or regulation of extracellular ions. As the species complexity increases, so does the functional and morphological complexity of astrocytes. For example, in fish and amphibians, these cells are involved in synaptic development and ion homeostasis, while in reptiles and birds, astrocytes regulate synaptic transmission and plasticity and are reported to be involved in complex behaviors. Other species like those belonging to mammals and, in particular, primates have a heterogeneous population of astrocytes, exhibiting region-specific functional properties. In primates, these cells are responsible for proper synaptic transmission, neurotransmitter release and metabolism, and higher cognitive functions like learning, memory, or information processing. This chapter highlights the well-established and somewhat conserved roles of astrocytes and astrocyte-neuron interactions across the evolution of both invertebrates and vertebrates.

Neural plasticity can be defined as the ability of neural circuits to be shaped by external and internal factors. It provides the brain with a capacity for functional and morphological remodelling, with many lines of evidence indicating that these changes are vital for learning and memory formation. The basis of this brain plasticity resides in activity- and experience-driven modifications of synaptic strength, including synaptic formation, elimination or weakening, as well as of modulation of neuronal population, which drive the structural reorganization of neural networks. Recent evidence indicates that brain-resident glial cells actively participate in these processes, suggesting that mechanisms underlying plasticity in the brain are multifaceted. Establishing the 'tripartite' synapse, the role of astrocytes in modulating synaptic transmission in response to neuronal activity was recognized first. Further redefinition of the synapse as 'quad-partite' followed to acknowledge the contribution of microglia which were revealed to affect numerous brain functions via dynamic interactions with synapses, acting as 'synaptic sensors' that respond to neuronal activity and neurotransmitter release, as well as crosstalk with astrocytes. Early studies identified microglial ability to dynamically survey their local brain environment and established their integral role in the active interfacing of environmental stimuli (both internal and external), with brain plasticity and remodelling. Following the introduction to neurogenesis, this chapter details the role that microglia play in regulating neurogenesis in adulthood, specifically as it relates to learning and memory, as well as factors involved in modulation of microglia. Further, a microglial perspective is introduced for the context of environmental enrichment impact on neurogenesis, learning and memory across states of stress, ageing, disease and injury.

Pediatric traumatic brain injury (TBI) is a significant healthcare issue, but potential treatments are absent despite robust investigation in several clinical trials. Factors attributed to clinical TBI, such as heterogeneity of injury and single-dose pharmacological treatments as well as timing of administration, may be reasons for the negative studies. Preclinical models of TBI can reduce some of the impediments by highlighting differences in injury depending on injury severity and location and by conducting dose response studies, thus providing better therapeutic targets and pharmacological profiles for clinical use. In this chapter, there were sufficient reports to make comparisons between the models in terms of pathophysiology, behavioral dysfunction, and the efficacy of therapeutic interventions. The models used to date include controlled cortical impact (CCI), weight drop, fluid percussion, and abusive head trauma. Several therapeutics were identified after CCI injury but none in the other models, which underscores the need for studies evaluating the therapies reported after CCI injury as well as novel potential approaches.

Traumatic brain injuries are increasingly common in older adults and represent a substantial source of morbidity and mortality for this population. In addition to the impact from the primary insult, TBI can lead to a variety of chronic neurocognitive conditions including dementia, depression, and sleep disturbances. When caused by TBI, these conditions differ importantly from their non-TBI-related counterparts. Much about how TBI relates to the development of these conditions is unknown, and more research is needed to further elucidate optimal treatment strategies.

After the previous sections on "Fractals: What and Why?," the last section of this book covers the software tools necessary to perform computational fractal-based analysis, with special emphasis on its applications into the neurosciences. The use of ImageJ and MATLAB, as well as other software packages, is reviewed. The current and future applications of fractal modeling in bioengineering and biotechnology are discussed as well. Perspectives on the translation of merging fractals with artificial intelligence-based methods with the final aim of pattern discrimination in neurological diseases by means of a unified fractal model of the brain are also given. Moreover, some new translational applications of fractal analysis to the neurosciences are presented, including eye tracking analysis, cognitive neuroscience, and music.

Brain parenchyma microvasculature is set in disarray in the presence of tumors, and malignant brain tumors are among the most vascularized neoplasms in humans. As microvessels can be easily identified in histologic specimens, quantification of microvascularity can be used alone or in combination with other histological features to increase the understanding of the dynamic behavior, diagnosis, and prognosis of brain tumors. Different brain tumors, and even subtypes of the same tumor, show specific microvascular patterns, as a kind of "microvascular fingerprint," which is particular to each histotype. Reliable morphometric parameters are required for the qualitative and quantitative characterization of the neoplastic angioarchitecture, although the lack of standardization of a technique able to quantify the microvascular patterns in an objective way has limited the "morphometric approach" in neuro-oncology.In this chapter, we focus on the importance of computational-based morphometrics, for the objective description of tumoral microvascular fingerprinting. By also introducing the concept of "angio-space," which is the tumoral space occupied by the microvessels, we here present fractal analysis as the most reliable computational tool able to offer objective parameters for the description of the microvascular networks.The spectrum of different angioarchitectural configurations can be quantified by means of Euclidean and fractal-based parameters in a multiparametric analysis, aimed to offer surrogate biomarkers of cancer. Such parameters are here described from the methodological point of view (i.e., feature extraction) as well as from the clinical perspective (i.e., relation to underlying physiology), in order to offer new computational parameters to the clinicians with the final goal of improving diagnostic and prognostic power of patients affected by brain tumors.