Progress in molecular biology and translational science
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Prog Mol Biol Transl Sci · Jan 2020
ReviewIn vitro models for ASD-patient-derived iPSCs and cerebral organoids.
Autism spectrum disorder (ASD) is a set of pervasive neurodevelopmental disorders. The causation is multigenic in most cases, which makes it difficult to model the condition in vitro. ⋯ This chapter aims to give an overview of the iPSC technology for generating neural cells and cerebral organoids as models for neurodevelopment and how these models are utilized in the study of ASD. The combination of iPSC technology and the genetic modification tool CRISPR/Cas9 is described, and current limitations and future perspectives of iPSC technology is discussed.
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Various genetic and environmental factors have been suggested to cause autism spectrum disorders (ASDs). A variety of animal models of ASDs have been developed and used to investigate the mechanisms underlying the pathogenesis of ASDs. These animal models have contributed to clarifying that abnormalities in neuronal morphology and neurotransmission are responsible for the onset of ASDs. ⋯ In this chapter, we first introduce a list of commonly available animal models of ASDs and describe the validity of each model from the viewpoint of behaviors and neuroanatomy. We next detail the malfunction of microglia that has been reported in animal models of ASDs and discuss the roles of microglia in ASD pathogenesis. We will further propose possible therapeutic strategies to tackle ASDs by controlling microglial functions.
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Prog Mol Biol Transl Sci · Jan 2019
ReviewMagnetoencephalography applied to the study of Alzheimer's disease.
Magnetoencephalography (MEG) is a relatively modern neuroimaging technique able to study normal and pathological brain functioning with temporal resolution in the order of milliseconds and adequate spatial resolution. Although its clinical applications are still relatively limited, great advances have been made in recent years in the field of dementia and Alzheimer's disease (AD) in particular. In this chapter, we briefly describe the physiological phenomena underlying MEG brain signals and the different metrics that can be computed from these data in order to study the alterations disrupting brain activity not only in demented patients, but also in the preclinical and prodromal stages of the disease. ⋯ To this aim, findings from different approaches such as resting state or during the performance of different cognitive paradigms are discussed. Lastly, there is an increasing interest in current scientific literature in promoting interventions aimed at modifying certain lifestyles, such as nutrition or physical activity among others, thought to reduce or delay AD risk. We discuss the utility of MEG as a potential marker of the success of such interventions from the available literature.
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Prog Mol Biol Transl Sci · Jan 2017
ReviewThe Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs.
Normal gas exchange after birth requires functional lung alveolar units that are lined with epithelial cells, parts of which are intricately fused with microvascular capillaries. A significant phase of alveolar lung development occurs in the perinatal period, continues throughout early stages in life, and requires activation of matrix-remodeling enzymes. Failure to achieve an optimum number of alveoli during lung maturation can cause several untoward medical consequences including disabling obstructive and/or restrictive lung diseases that limit physiological endurance and increase mortality. ⋯ Broadly, with the exception of MMP2 and MMP14, most deletional mutations of MMPs fail to perturb lung development; however, their individual absence can alter the pathophysiology of respiratory diseases. Specifically, under stressed conditions such as acute respiratory infection and allergic inflammation, MMP2 and MMP9 can play a protective role through bacterial clearance and production of chemotactic gradient, while loss of MMP12 can protect mice from smoke-induced lung disease. Therefore, better understanding of the expression and function of MMPs under normal lung development and their resurgence in response respiratory diseases could provide new therapeutic options in the future.