BPharm (Rhodes University, South Africa, 1987)
DPhil (Oxford University, UK, 1997)
Investigating the effect of lithium on dopamine signalling through glycogen synthase kinase 3β (GSK-3β)
The aim of this study is to further our understanding of the mechanism of action of the mood stabiliser lithium. Two neurobiological effects of the mood stabiliser lithium which may be relevant to its therapeutic mechanism of action are attenuation of dopamine neurotransmission and inhibition of the intracellular signalling enzyme glycogen synthase kinase 3β (GSK-3β). Recent reports that GSK-3β is involved dopamine receptor signalling suggest that these two neurobiological effects of lithium may be related. In this project we are investigating the effect of lithium on dopamine receptor signalling through GSK-3β.
Does exercise attenuate the effect of diabetes on cognition and brain neuropathology?
Diabetes is a major risk factor associated with neurodegenerative disorders including dementias. We hypothesise that lifestyle factors such as exercise and diet can influence this risk. In this study we are using a mouse model of type I diabetes to determine how exercise versus sedentary behaviour affects diabetes-induced deficits in spatial and non-spatial memory and changes in markers of neurodegeneration in the brain. (In collaboration with Dr Sasha Gartside and Dr Elizabeta Mukaetova-Ladinska)
Interpreting the effects of lithium on the structural neuroimaging signal.
There is a growing body of evidence from structural neuroimaging studies in bipolar patients that chronic treatment with the mood stabiliser lithium increases grey matters volume in a number of brain areas. The origin of this apparent increase in grey matter is unclear- neurotrophic effects of lithium on the brain tissue is one obvious possibility. However, another possibility is that the increase in grey matter is not ‘real’, but is rather an artefact produced by lithium’s interaction with water molecules during the neuroimaging scan. In this project we are using MRI in laboratory rodents to investigate this and determine whether the increase in grey matter volume detected in neuroimaging studies is indeed an indication of neurotrophism. (In collaboration with Prof Nicol Ferrier, Prof Andy Blamire and Dr David Cousins)
Understanding the neurobiology of cognitive abnormalities in psychiatric disorders.
Pharmacological and lesion studies have highlighted the role for the prefrontal cortex in a number of cognitive functions including executive function, attention, planning and impulse control. These processes are altered in a number of disorders including affective disorders, schizophrenia and addiction. There are a number of manipulations that can affect the structure of prefrontal cortical neurones. For example, chronic glucocorticoids and stress have all been shown to cause dendritic pruning in PFC neurones. However, the functional consequences of these structural changes in particular in relation to cognition are unclear. This project seeks to explore the relationships between neuronal structure and function in the PFC and PFC-mediated cognitive performance. We are testing the hypotheses that changes in neuronal structure necessarily result in changes in cognition and that subtle changes in dendritic branching caused by factors relevant to the aetiology of affective disorders (e.g. stress or corticosterone) are sufficient to cause significant cognitive changes. (In collaboration with Dr Sasha Gartside, Joanne Wallace)
Using PET to study 5-HT function
A study aimed at developing novel PET ligands which can be used to study presynaptic 5-HT function (in Collaboration with Dr Mike Carroll, Dr Sasha Gartside, Caroline McCardle)
I teach pharmacology and psychopharmacology on a number of degree courses including, BSc Honours in Pharmacology, BSc Honours in Biomedical Sciences and MBBS.
Module Leader for:
Stage 3 Neuropharmacology (PED3008)
Stage 3 Pharmacology techniques (PED3001)
Chair Pharmacology Curriculum Committee