Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities.

The use of zebrafish (Danio rerio) in biomedical research has expanded at a tremendous rate over the last two decades. Along with increases in laboratories using this model, we are discovering new and important diseases. We review here the important pathogens and diseases based on some 20 years of research and findings from our diagnostic service at the NIH-funded Zebrafish International Resource Center. Descriptions of the present status of biosecurity programmes and diagnostic and treatment approaches are included. The most common and important diseases and pathogens are two parasites, Pseudoloma neurophilia and Pseudocapillaria tomentosa, and mycobacteriosis caused by Mycobacterium chelonae, M. marinum and M. haemophilum. Less common but deadly diseases are caused by Edwardsiella ictaluri and infectious spleen and kidney necrosis virus (ISKNV). Hepatic megalocytosis and egg-associated inflammation and fibroplasia are common, apparently non-infectious, in zebrafish laboratories. Water quality diseases include supersaturation and nephrocalcinosis. Common neoplasms are spindle cell sarcomas, ultimobranchial tumours, spermatocytic seminomas and a small-cell carcinoma that is caused by a transmissible agent. Despite the clear biosecurity risk, researchers continue to use fish from pet stores, and here, we document two novel coccidia associated with significant lesions in zebrafish from one of these stores.

Health monitoring and disease prevention at the Zebrafish International Resource Center.

In this chapter we review the components of the fish health program at the Zebrafish International Resource Center. We describe health-monitoring strategies to assess individual and colony health, practices to prevent the spread of pathogens within the fish colony, and a biosecurity program designed to prevent entry of new fish pathogens. While this program is designed for a facility on a recirculating water system with expectations of high volumes of import and export, many of the components can be directly applied or modified for application in facilities of different sizes and with other programmatic goals.

Primary intestinal and vertebral chordomas in laboratory zebrafish (Danio rerio).

Chordomas are uncommon neoplasms arising from notochord remnants, most commonly occurring in the axial skeleton. Extraskeletal soft tissue chordomas are rare primary tumors, and primary alimentary tract chordomas have not been reported. Herein we report 24 cases of spontaneous primary intestinal chordomas in zebrafish, as well as 9 spontaneous vertebral chordomas. Both intestinal and vertebral tumors showed invasive behavior, although more commonly in the latter. In all cases of primary intestinal chordomas, there was no axial or peripheral skeletal or other nonvisceral involvement. Although uncommon, intestinal chordomas represent a unique background lesion in aged zebrafish.

Malignant dysembryoplastic neuroepithelial tumour in a zebrafish (Danio rerio).

Neuroectodermal tumours in man, including medulloblastoma, medulloepithelioma, neuroblastoma, esthesioneuroblastoma, primitive neuroectodermal tumour and dysembryoplastic neuroepithelial tumour, typically occur in children and young adults. These tumour types are occasionally observed in juvenile and adult zebrafish (Danio rerio) either as induced tumours in carcinogen-exposed zebrafish or as an incidental finding in zebrafish≥2years of age. An adult zebrafish submitted for routine histological examination was sent for a second opinion consultation after an uncharacteristic brain mass was identified. Microscopically, the expansile and infiltrative extracortical mass arising from the cerebellum had a diffuse microcystic pattern with solid hypercellular regions occupying 80% of the extrameningeal space and effacing the endomeninx and significantly displacing the metencephalon. The mass was composed of dense sheets of oligodendrocyte-like cells, random neurons and pseudocysts containing 'floating neurons' within a scant mucinous matrix. Neoplastic cells demonstrated positive perinuclear and intracytoplasmic expression of S-100. Malignant dysembryoplastic neuroepithelial tumour was diagnosed based on the histological features of the brain mass, which were indistinguishable from the human tumour. To our knowledge, this is the first report of a dysembryoplastic neuroepithelial tumour in a zebrafish.

Nicotine's effect on neural and cognitive functioning in an aging population.

Tobacco is a dangerous and addictive drug being consumed by more than 13% of Americans over the age of 65. Of the people in this cohort it has been estimated that between 24% and 85% experience some form of age related cognitive decline and 30-50% of the population will be diagnosed with Alzheimer's disease by the age of 85. Recent advances in nicotine research have pointed to a number of cognitive and neurological benefits that have been linked to the ingestion of nicotine. These discoveries hold the potential of new drugs and therapies that retain and improve upon nicotine's benefits while eliminating the negative impact that both nicotine and tobacco possess. This article examines cognitive decline in the elderly and looks at nicotine's potential role in ameliorating this decline. In service to this, the neurological and cognitive actions of nicotine are reviewed, as are theories on the neurological degeneration associated with Alzheimer's disease (AD).

Characterization of an Escherichia coli mutant deficient in dihydrolipoyl dehydrogenase activity.

A mutant of Escherichia coli deficient in dihydrolipoyl dehydrogenase (DHL) activity has been isolated and its characteristics have been studied. The activities of the pyruvic dehydrogenase (PDC) and alpha-ketoglutaric dehydrogenase complexes (KDC) are not present in extracts of the mutant unless purified dihydrolipoyl dehydrogenase is added. Experiments with antiserum to DHL have shown that cross-reacting material exists in mutant extracts. This suggests that the dihydrolipoyl dehydrogenase mutation (dhl(-)) is a missense structural mutation. The mutation maps very close to, if not adjacent to, the ace loci, and is not linked to the suc loci. This means the dhl locus is grouped with the genes for the other components of the PDC and not with the genes for KDC. The mutation is also transducible into prototrophic strains, demonstrating that no prior mutation is necessary for the DHL activity deficiency to exist. This evidence is consistent with the idea that there is only one gene for DHL and is supported by previous biochemical studies which have shown that DHL preparations from either enzyme complex are electrophoretically and immunochemically indistinguishable. Possible mechanisms for the genetic and metabolic control of DHL, PDC, and KDC are discussed.