Zebrafish as a tractable model of human cardiovascular disease.

Mammalian models including non-human primates, pigs and rodents have been used extensively to study the mechanisms of cardiovascular disease. However, there is an increasing desire for alternative model systems that provide excellent scientific value while replacing or reducing the use of mammals. Here, we review the use of zebrafish, Danio rerio, to study cardiovascular development and disease. The anatomy and physiology of zebrafish and mammalian cardiovascular systems are compared, and we describe the use of zebrafish models in studying the mechanisms of cardiac (e.g. congenital heart defects, cardiomyopathy, conduction disorders and regeneration) and vascular (endothelial dysfunction and atherosclerosis, lipid metabolism, vascular ageing, neurovascular physiology and stroke) pathologies. We also review the use of zebrafish for studying pharmacological responses to cardiovascular drugs and describe several features of zebrafish that make them a compelling model for in vivo screening of compounds for the treatment cardiovascular disease. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Nitric oxide interacts with monoamine oxidase to modulate aggression and anxiety-like behaviour.

Nitric oxide (NO) is a gaseous neurotransmitter that has important behavioural functions in the vertebrate brain. In this study we compare the impact of decreased nitric NO signalling upon behaviour and neurobiology using both zebrafish and mouse. nitric oxide synthase mutant (nos1-/-) zebrafish show significantly reduced aggression and an increase in anxiety-like behaviour without altered production of the stress hormone cortisol. Nos1-/- mice also exhibit decreased aggression and are hyperactive in an open field test. Upon reduction of NO signalling, monoamine neurotransmitter metabolism is reduced as a consequence of decreased Monoamine oxidase activity. Treatment of nos1-/- zebrafish with the 5-HT receptor 1A agonist 8-OH-DPAT rescues aggression and some aspects of anxiety-like behaviour. Taken together, the interplay between NO and 5-HT appears to be critical to control behaviour. Our cross-species approach challenges the previous notion that reduced neuronal NOS leads to increased aggression. Rather, Nos1 knock-out can also lead to decreased aggression in some situations, a finding that may have implications for future translational research.

Exposure and risk factors to coxiella burnetii, spotted fever group and typhus group Rickettsiae, and Bartonella henselae among volunteer blood donors in Namibia.

BACKGROUND: The role of pathogen-mediated febrile illness in sub-Saharan Africa is receiving more attention, especially in Southern Africa where four countries (including Namibia) are actively working to eliminate malaria. With a high concentration of livestock and high rates of companion animal ownership, the influence of zoonotic bacterial diseases as causes of febrile illness in Namibia remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the study was to evaluate exposure to Coxiella burnetii, spotted fever and typhus group rickettsiae, and Bartonella henselae using IFA and ELISA (IgG) in serum collected from 319 volunteer blood donors identified by the Blood Transfusion Service of Namibia (NAMBTS). Serum samples were linked to a basic questionnaire to identify possible risk factors. The majority of the participants (64.8%) had extensive exposure to rural areas or farms. Results indicated a C. burnetii prevalence of 26.1% (screening titre 1∶16), and prevalence rates of 11.9% and 14.9% (screening titre 1∶100) for spotted fever group and typhus group rickettsiae, respectively. There was a significant spatial association between C. burnetii exposure and place of residence in southern Namibia (P<0.021). Donors with occupations involving animals (P>0.012), especially cattle (P>0.006), were also significantly associated with C. burnetii exposure. Males were significantly more likely than females to have been exposed to spotted fever (P<0.013) and typhus (P<0.011) group rickettsiae. Three (2.9%) samples were positive for B. henselae possibly indicating low levels of exposure to a pathogen never reported in Namibia. CONCLUSIONS/SIGNIFICANCE: These results indicate that Namibians are exposed to pathogenic fever-causing bacteria, most of which have flea or tick vectors/reservoirs. The epidemiology of febrile illnesses in Namibia needs further evaluation in order to develop comprehensive local diagnostic and treatment algorithms.

Risk assessment of flavivirus transmission in Namibia.

The role of arboviruses causing acute febrile illness in sub-Saharan Africa is receiving more attention. Reports of dengue in tourists were published nearly 10 years ago in Namibia, but the current epidemiology of arboviruses is unknown and surveys of mosquito vectors have not been carried out since the 1950s. To begin addressing this knowledge gap, a prospective cross-sectional study was conducted using samples from volunteer blood donors linked to questionnaire. Serum samples were tested using a Dengue IgG Indirect ELISA which measured exposure to dengue virus/flaviviruses. Entomological samples were collected from tires during the rainy season (February-March 2012) in six locations across Namibia's capital city, Windhoek. Among 312 blood donors tested, 25 (8.0%) were positive for dengue virus/flavivirus exposure. The only significant risk factor was age group with high exposure rates among those older than 50 (29%) compared with those below 40 years old (between 2.9% and 8.3%) (P<0.002). Larvae and pupae of Aedes aegypti and Culex pipiens complex accounted for 100% of the 2751 samples collected, of which only 12.2% (n=336) were Ae. aegypti. Each site demonstrated high variability of species composition between sampling times. While the significant dengue virus/flavivirus exposure rate among those above 50 years old is likely indicative of the West Nile epidemic in the 70s and 80s, the low exposure among those under 50 suggests that flaviviruses are still circulating in Namibia. While Ae. aegypti and C. pipiens sp. may play a role in future epidemics, the significance of presence may be reduced due to short rain periods, dry, arid, cold winters and policies and social understandings that limit non-structured storage and use of tires in low income areas. Future studies should further characterize the circulating arboviruses and investigate mosquito ecology nationally to map areas at higher risk for future arbovirus outbreaks.