My research spans the neurobiology of synaptic transmission and plasticity associated with cellular models of learning and addiction. My specific interests are in the mechanisms that underlie both hippocampal long-term potentiation (LTP) and Long-term Depression (LTD). In view of the alterations in cognition associated with Alzheimer’s disease (AD), my group has investigated the effects of beta amyloid peptide (A?), known to be associated with this neurodegenerative disease. Research includes electrophysiological recording from the rat hippocampus in vivo following icv. injection of beta amyloid peptide (Aß) and subsequent biochemical analysis of the stimulated brain tissue to examine changes in kinase and cytokine activity, using Western blotting techniques and phospho-specific antibodies and ELISA . Electrophysiological recording from in vitro hippocampal slices to investigate the molecular mechanism of action of Aß. We have examined a) Aß-mediated activation of stress activated kinase c-jun-n-terminal kinase (JNK) by using a selective antagonist SP600125 and demonstrated that this kinase is involved in synaptic transmission and also in the neurotoxic effects of Aß. Interactions with the L-type voltage gated calcium channel by examining the effects of channel blockers that are presently used in the clinic. Evidence for an interaction between the high-affinity binding site on the beta 7-neuronal nicotinic receptor and Aß the alpha-7 nicotinic acetylcholine receptor. Effects of perixosome proliferator activated receptor (PPAR) agonists on Aß mediated deficits in hippocampal LTP .
WE have also investigated the effects of oligomeric beta amyloid on membrane PrPc and demonstrated it is required in order for Abeta to attenuate LT@P .Statins have also been shown to be neuroprotective and we subsequently used simvastatin to chronically treat a transgenic model of Alzheimer’s disease (APPswe/PS1dE9) and demonstrated improved synaptic plasticity and a change in biochemical signally towards the control following Simvastatin. The most recent and exciting research is focussed on the effects of the non-psychoactivve component of Cannabis Sativa: Cannabidiol. We have shown that it neuroprotective at low concentrations against the effects of beta amyloid peptide both in vitro and in vivo suggesting that this may be a therapy for Alzheimers disease.