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Mammalian central nervous system (CNS) has limited capacity for regeneration. CNS injuries cause life-long debilitation and lead to $50 billion in healthcare costs in U.S. alone each year. Despite numerous efforts in the last few decades, CNS-related injuries remain as detrimental as they were 50 years ago. Some functional recovery can occur, but most regeneration are limited by an extracellular matrix (ECM) that actively inhibits axonal repair and promotes glial scarring. In most tissues, the ECM is an architectural foundation that plays an active role in supporting cellular development and regenerative response after injury. In mammalian CNS, however, this is not the case - its composition is not conducive for regeneration, with various molecules restricting plasticity and neuronal growth. In fact, the CNS ECM alters its composition dramatically following injury to restrict regeneration and to prioritize containment of injury as well as preservation of intact neural circuitry. This leads us to hypothesize that the inhibitory extracellular environment needs be modified or supplemented to be more regeneration-permissive for significant CNS regeneration. Mammalian nervous tissue cannot provide such ECM, and synthesizing it in a laboratory is beyond current technology. Evolutionarily lower species possess remarkably regenerative neural tissue. For example, small fresh-water dwelling zebrafish ( Danio rerio ) can regenerate severed spinal cord, re-gaining full motor function in a week. We believe their ECM contributes to its regenerative capability and that it can be harnessed to induce more regeneration in mammalian CNS. This study shows that ECM derived from zebrafish brains promotes more neuronal survival and axonal network formation than the widely studied and available ECM derived from mammalian tissues such as porcine brains, porcine urinary bladder, and rat brains. We believe its regenerative potential, combined with its affordability, easy handling, and fast reproduction, will make zebrafish an excellent candidate as a novel ECM source. [ABSTRACT FROM AUTHOR]

Heart disease is the leading cause of mortality in the U.S. with approximately 610,000 people dying every year. Effective therapies for many cardiac diseases are lacking, largely due to an incomplete understanding of their genetic basis and underlying molecular mechanisms. Zebrafish (Danio rerio) are an excellent model system for studying heart disease as they enable a forward genetic approach to tackle this unmet medical need. In recent years, our team has been employing electrocardiogram (ECG) as an efficient tool to study the zebrafish heart along with conventional approaches, such as immunohistochemistry, DNA and protein analyses. We have overcome various challenges in the small size and aquatic environment of zebrafish in order to obtain ECG signals with favorable signal-to-noise ratio (SNR), and high spatial and temporal resolution. In this paper, we highlight our recent efforts in zebrafish ECG acquisition with a cost-effective simplified microelectrode array (MEA) membrane providing multi-channel recording, a novel multi-chamber apparatus for simultaneous screening, and a LabVIEW program to facilitate recording and processing. We also demonstrate the use of machine learning-based programs to recognize specific ECG patterns, yielding promising results with our current limited amount of zebrafish data. Our solutions hold promise to carry out numerous studies of heart diseases, drug screening, stem cell-based therapy validation, and regenerative medicine. [ABSTRACT FROM AUTHOR]

Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation. [ABSTRACT FROM AUTHOR]

The article reports on the gene selection method developed by two groups of research teams in the U.S. Researchers adopted chimaeric enzymes called zinc-finger nucleases to disrupt selected genes of the zebrafish which they chose as a laboratory model. Sharon Amacher and colleagues at the University of California in Berkeley used nucleases with four zinc fingers. They did not observe DNA breaks except on those they intended. Scot Wolfe and Nathan Lawson, along with colleagues at the University of Massachusetts Medical School in Worcester, also utilized three-finger nucleases and recorded off-target cleavage in about 1% to 5% of their zebrafish.