Disputation: Nancy Saana Banono
Doctoral candidate Nancy Saana Banono at NCMM and the Department of Pharmacy, Faculty of Mathematics and Natural Sciences, is defending the thesis "Functional analysis of psychiatric risk genes in zebrafish (Danio rerio): a focus on the L-type voltage-gated calcium channel subtypes Cav 1.2 and Cav 1.3" for the degree of Philosophiae Doctor.
Trial lecture - time and place
07.10.2021, 10.15, Auditorium 2, Pharmacy building
Cognitive dysfunctions in psychotic disorders
In her PhD thesis, Nancy and colleagues sought to understand the contributions of two calcium channel genes (CACNA1C and CACNA1D) toward the development of neuropsychiatric disorders. To help achieve their goal, they used zebrafish larvae that carry mutations in these genes. They discovered that when the functions of CACNA1C and CACNA1D are genetically perturbed, changes in expression of genes important for neuronal survival and function occur and the brain goes into a state of increased excitation, which may contribute to the plethora of behavioural defects observed in their mutant animals.
Main research findings
CACNA1C and CACNA1D are voltage-gated calcium channel genes that have been repeatedly associated with psychiatric disorders by various genomic studies. These genes are involved in gene expression regulation, neurotransmitter release and integration of dendritic information in the brain, but the mechanisms through which they cause disease are poorly understood.
The goal of this thesis was to characterise the effects of mutations in CACNA1C and CACNA1D on early brain function using three zebrafish mutant lines (one cacna1dand two cacna1c mutants) that were characterised through an arsenal of molecular, behavioural, neurophysiological and pharmacological methods.
Larval zebrafish with global cacna1da haploinsufficiency showed a hyperlocomotor phenotype that could be improved or reversed using the antipsychotics haloperidol and risperidone and the mood stabiliser, valproate. Furthermore, larvae with global loss-of-function (LOF) of cacna1c was associated with observable dysmorphologies, changes in downstream molecular targets, compensatory overexpression of cacna1d, and deficits in sensorimotor gating. In addition, spectral analysis of local field potential recordings and neurotransmitter analysis revealed gross neural excitability in the cacna1c LOF mutants.
Together, we have shown that mutations that alter the function of cacna1da and cacna1c lead to a wide-range of phenotypes reminiscent of relevant functional domains observed in psychiatric disorders.
Candidate contact information
Mobile: +47 48342688
Professor Gregers Wegener, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus Univesity
Associate professor Florence Kermen, Department of Biology, Norwegian University of Science and Technology - NTNU
Professor Ragnhild Elisabeth Heimtun Paulsen, Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo
Associate professor Camila E. Esguerra, Section for Pharmacology and Pharmaceutical Sciences, Department of Pharmacy, University of Oslo
Professor Marianne Fyhn, Section for Physiology and Cell Biology, Department of Biosciences, University of Oslo
Professor Ole Andreassen, Institute of Clinical Medicine, Oslo University Hospital
Chair of defence
Professor Sverre Arne Sande, Department of Pharmacy, University of Oslo