Caroline Helen Brennan

Caroline Helen Brennan
Queen Mary, University of London | QMUL · School of Biological and Chemical Sciences

PhD

About

135
Publications
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Publications

Publications (135)
Article
Full-text available
An ability to estimate quantities, such as the number of conspecifics or the size of a predator, has been reported in vertebrates. Fish, in particular zebrafish, may be instrumental in advancing the understanding of magnitude cognition. We review here the behavioral studies that have described the ecological relevance of quantity estimation in fish...
Article
Full-text available
A sense of non-symbolic numerical magnitudes is widespread in the animal kingdom and has been documented in adult zebrafish. Here, we investigated the ontogeny of this ability using a group size preference (GSP) task in juvenile zebrafish. Fish showed GSP from 21 days post-fertilization and reliably chose the larger group when presented with discri...
Article
Full-text available
Psychiatric disorders represent a significant burden in our societies. Despite the convincing evidence pointing at gene and gene-environment interaction contributions, the role of genetics in the aetiology of psychiatric disease is still poorly understood. Forward genetic screens in animal models have helped elucidate causal links. Here we discuss...
Article
Full-text available
ANKK1 is a member of the receptor-interacting protein serine/threonine kinase family, known to be involved in cell proliferation, differentiation and activation of transcription factors. Genetic variation within the ANKK1 locus is suggested to play a role in vulnerability to addictions. However, ANKK1 mechanism of action is still poorly understood....
Article
Full-text available
Developmental consequences of prenatal drug exposure have been reported in many human cohorts and animal studies. The long-lasting impact on the offspring—including motor and cognitive impairments, cranial and cardiac anomalies and increased prevalence of ADHD—is a socioeconomic burden worldwide. Identifying the molecular changes leading to develop...
Article
Pollution is harmful to human physical health and wellbeing. What is less well established is the relationship between adolescent mental health – a growing public health concern – and pollution. In response, we systematically reviewed studies documenting associations between pollution and mental health in adolescents. We searched Africa Wide, Medli...
Article
Full-text available
Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and long-term effects of developmental exposure to low dose...
Article
Full-text available
We found a region of the zebrafish pallium that shows selective activation upon change in the numerosity of visual stimuli. Zebrafish were habituated to sets of small dots that changed in individual size, position, and density, while maintaining their numerousness and overall surface. During dishabituation tests, zebrafish faced a change in number...
Article
Background: Nicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking. Aims: We evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal. Methods: Zeb...
Article
Full-text available
An interactive effect between nicotine and 3,4-methylenedioxymethamphetamine (MDMA) has been reported but the mechanism underlying such interaction is not completely understood. This study used zebrafish to explore gene expression changes associated with altered sensitivity to the rewarding effects of MDMA following 2-week exposure to nicotine and...
Article
Full-text available
Background Whilst there is little uncertainty about the deleterious impact of pollution on human and planetary health, pollution’s impact on adolescent mental health is less well understood. This is particularly true for young people in underdeveloped and developing world contexts, about whom research is generally lacking. Furthermore, although ado...
Preprint
Full-text available
Non-symbolic number cognition based on an approximate sense of magnitude has been documented in adult zebrafish. Here we investigated the ontogeny of this ability using a group size preference task in juvenile zebrafish. Fish showed group size preference from 26 days post fertilization (dpf) and from 27 dpf fish reliably chose the larger group when...
Article
Full-text available
Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene wi...
Article
Full-text available
Individual differences in personality are associated with variation in healthy aging. Health behaviours are often cited as the likely explanation for this association; however, an underlying biological mechanism may also exist. Accelerated leukocyte telomere shortening is implicated in multiple age-related diseases and is associated with chronic ac...
Article
Brain lateralization refers to hemispheric asymmetries in functions and/or neuroanatomical structures. Functional specialization in non-human animals has been mainly inferred through observation of lateralized motor responses and sensory perception. Only in a few cases has the influence of brain asymmetries on behaviour been described. Zebrafish ha...
Preprint
Full-text available
Non-symbolic number cognition based on an approximate sense of magnitude has been documented in zebrafish. Here we investigated for the first time its neural bases. Zebrafish were habituated to a set of three or nine small dots associated with food reward. During habituation trials, the dots changed in their individual size, position and density ma...
Article
Full-text available
Mastering relational concepts and applying them to different contexts presupposes abstraction capacities and implies a high level of cognitive sophistication. One way to investigate extrapolative abilities is to assess cross-dimensional application of an abstract relational magnitude rule to new domains. Here we show that angelfish initially traine...
Article
Full-text available
While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smokin...
Preprint
Full-text available
Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene wi...
Article
Full-text available
Early life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish (Danio rerio) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant behav...
Preprint
Full-text available
Background Whilst there is little uncertainty about the deleterious impact of pollution on human and planetary health, pollution’s impact on child and adolescent mental health is less well understood. This is particularly true for young people in underdeveloped and developing world contexts, about whom research is generally lacking. Furthermore, al...
Preprint
Full-text available
Telomere length reflects cellular ageing. Increased telomere shortening in leukocytes is associated with a range of neurodegenerative and cardiovascular diseases, the onset and progression of which may be mediated by behavioural traits such as anxiety and stress reactivity. However, the effects of the hypothalamus-pituitary-adrenal axis stress resp...
Article
Full-text available
Evidence has shown that a variety of vertebrates, including fish, can discriminate collections of visual items on the basis of their numerousness using an evolutionarily conserved system for approximating numerical magnitude (the so-called Approximate Number System, ANS). Here we combine a habituation/dishabituation behavioural task with molecular...
Article
Full-text available
To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 i...
Article
Full-text available
To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 i...
Article
Full-text available
To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 i...
Preprint
Full-text available
Early-life stress (ELS) is defined as a short or chronic period of trauma, environmental or social deprivation, which can affect different neurochemical and behavioral patterns during adulthood. Zebrafish ( Danio rerio ) have been widely used as a model system to understand human neurodevelopmental disorders and display translationally relevant beh...
Preprint
Full-text available
While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smokin...
Article
As a model organism, zebrafish have much to offer neuroscientific research and they are increasingly being used in behavioral neuroscience, for example to study the genetics of learning and memory. As fish are often considered “less clever” than mammals, it is important to understand how they learn and to establish optimal testing conditions. In th...
Preprint
Full-text available
BACKGROUND: Although there is clear evidence of genetic contributions to susceptibility to nicotine addiction, it has proved difficult to identify causal alleles and pathways from studies in humans. Mutagenesis in model species generates strong phenotypes not present in wildtype populations and can be used to identify biological mechanisms underlyi...
Article
Full-text available
Regulatory agencies recommend that centrally-active drugs are tested for abuse potential prior to approval. Standard preclinical assessments are conducted in rats or non-human primates (NHPs). This study evaluated the ability of the zebrafish conditioned place preference (CPP) model to predict human abuse outcomes. Twenty-seven compounds from a var...
Preprint
Full-text available
Zebrafish are an important model species with unparalleled potential to advance understanding of the genetics and neurobiology of behaviour through genetic and pharmacological screening and mutant analysis. However, advances using this species have been limited by the lack of robust, standardised methodology and equipment suitable for assessing adu...
Chapter
Full-text available
With lifespans rapidly increasing worldwide there has been a marked increase in age-related diseases—particularly those affecting cognition—that place a major socioeconomic burden on society. Despite this, much of what occurs during the aging process at a molecular level is poorly understood, facilitating the need for a greater understanding of the...
Article
Full-text available
Nature Communications 7 Article number:11942 (2016); Published 23 June 2016; Updated 21 July 2016 The original version of this Article contained an error in the spelling of the author Luisa Robbez-Masson, which was incorrectly given as Luisa Robert-Masson. This has now been corrected in both the PDFand HTML versions of the Article.
Article
Full-text available
Receptor tyrosine kinases (RTKs) and integrins cooperate to stimulate cell migration and tumour metastasis. Here we report that an integrin influences signalling of an RTK, c-Met, from inside the cell, to promote anchorage-independent cell survival. Thus, c-Met and β1-integrin co-internalize and become progressively recruited on LC3B-positive 'auto...
Data
Supplementary Figures 1-11 and Supplementary Table 1
Data
c-Met-GFP expressing cells loose adherence. c-Met-GFP cells were cultured on plastic, tetracycline (0.1 μg/ml) added and a time-lapse low-light movie performed for 16 h. A fluorescent (GFP) picture and a phase picture were taken every 10 min. S3: GFP; S4: phase.
Data
Results of colocalization analysis of the confocal images shown was calculated with the JaCoP plugin1 for ImageJ (National Institutes of Health, Bethesda). The co-localization index is represented by Pearson's coefficient calculated following Costes randomization (200 cycles) and automatic threshold calculation. The distribution of Pearson's coeffi...
Data
Co-trafficking of HGF-AlexaFluor-555 bound c-Met and β1- integrin. MDA-MB-468 cells were cultured on a MatTek dish and were surface labelled with an Alexa Fluor 488-labelled total β1 integrin antibody (K20) for 1 h on ice. After washing with cold growth medium, cells were incubated 10 min with HGF-AlexaFluor-555 on ice, washed with cold growth medi...
Data
- c-Met-GFP expressing cells loose adherence. c-Met-GFP cells were cultured on plastic, tetracycline (0.1 μg/ml) added and a time-lapse low-light movie performed for 16 h. A fluorescent (GFP) picture and a phase picture were taken every 10 min. S3: GFP; S4: phase.
Data
Co-trafficking of HGF-AlexaFluor-555 bound c-Met and a5 integrin-GFP. β1A cells were transfected with a5-integrin-GFP and 24 h later incubated with HGF-AlexaFluor- 555 for 10 min and washed three times. The movie was started at 30 min post-HGF (thus postendocytosis) and lasted 22 min.
Data
- c-Met-GFP traffics constitutively c-Met-GFP cells were cultured on plastic coated with Poly-L-lysine in presence of tetracycline (0.1 μg/ml) for 16 h. A single confocal section of the same cells (GFP) was acquired every 30 sec during 1 h.
Article
Background Impulsivity is poorly planned, premature or inappropriate behaviour, and deficits in impulse control are linked to a number of neuropsychiatric disorders. There are a number of theories relating to the neural basis of impulsivity, but the precise molecular mechanisms of impulse control are not clearly understood. Motor impulsivity has be...
Article
Full-text available
Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel...
Article
Full-text available
In zebrafish developmentally exposed to ambient ethanol (20mM-50mM) 1-9 days post fertilization (dpf), the cortisol response to stress has been shown to be significantly attenuated in larvae, juveniles and 6 month old adults. These data are somewhat at variance with similar studies in mammals, which often show heightened stress responses. To test w...
Article
Full-text available
Cellular and molecular processes that mediate individual variability in impulsivity, a key behavioral component of many neuropsychiatric disorders, are poorly understood. Zebrafish heterozygous for a nonsense mutation in ache (ache (sb55/+)) showed lower levels of impulsivity in a 5-choice serial reaction time task (5-CSRTT) than wild type and ache...
Article
Background: Individuals with severe generalized recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering disorder caused by mutations in the COL7A1 gene, develop unexplained aggressive squamous cell carcinomas (SCC). Here we report that loss of type VII collagen (Col7) in SCC results in increased TGFβ signaling and angiogenesis i...
Article
Full-text available
Background: Ethanol exposure during pregnancy is one of the leading causes of preventable birth defects, leading to a range of symptoms collectively known as fetal alcohol spectrum disorder. More moderate levels of prenatal ethanol exposure lead to a range of behavioural deficits including aggression, poor social interaction, poor cognitive perfor...
Article
Speed–accuracy trade-offs are well studied in human decision making, but we are only beginning to understand how such trade-offs affect other animals. Similarly, it is poorly understood how consistent individual differences in decision making are influenced by their social context. Here we investigated whether zebrafish, Danio rerio, show individua...
Article
Full-text available
Parallel visual search mechanisms have been reported previously only in mammals and birds, and not animals lacking an expanded telencephalon such as bees. Here we report the first evidence for parallel visual search in fish using a choice task where the fish had to find a target amongst an increasing number of distractors. Following two-choice disc...
Article
Full-text available
Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CN...
Article
Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have...