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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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.
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Prog Mol Biol Transl Sci · Jan 2016
ReviewGH and Pituitary Hormone Alterations After Traumatic Brain Injury.
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. ⋯ Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI.
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Prog Mol Biol Transl Sci · Jan 2015
ReviewCommonalities between pain and memory mechanisms and their meaning for understanding chronic pain.
Pain sensing neurons in the periphery (called nociceptors) and the central neurons that receive their projections show remarkable plasticity following injury. This plasticity results in amplification of pain signaling that is now understood to be crucial for the recovery and survival of organisms following injury. These same plasticity mechanisms may drive a transition to a nonadaptive chronic pain state if they fail to resolve following the termination of the healing process. ⋯ Here those mechanisms, their commonalities and subtle differences, will be highlighted and their role in causing chronic pain will be discussed. Arising from these data is the striking argument that chronic pain is a disease of the nervous system, which distinguishes this phenomena from acute pain that is frequently a symptom alerting the organism to injury. This argument has important implications for the development of disease modifying therapeutics.