Does reduced lipid metabolism lead to attention and memory problems?
Lab rotation project description
In this rotation the student will join an interdisciplinary project investigating the role of lipids in cognitive function. The overall aim of this project is to test whether changes in lipids are causally related to the memory and attention disruptions that we have found using a genetically modified mouse model of reduced neuregulin function.
The student will optionally learn how to measure behaviour such as prepulse inhibition in mice and analyse these datasets using statistics. The student will use RNA extracted from mouse brain to investigate expression of genes involved in lipid metabolism and investigate whether these are associated with any behavioural changes detected.
This will provide training in in vivo skills, animal behaviour, statistics, database handling, general molecular laboratory skills including RNA extraction and quantitative PCR.
Molecules, Cells and Organisms
Psychology & Pharmacy
LR1, LR2, LR3
Linked PhD Project Outline
There is considerable genetic and pathologic evidence for an association between dysregulation of the developmental gene neuregulin 1 (NRG1) and schizophrenia. The underlying molecular and cellular mechanisms are not known. In previous studies in mutant mice we found that heterozygous Nrg1 mutant mice with reduced neuregulin function from birth, demonstrated deficits in pre-pulse inhibition, a measure of attention and a sex-specific (males only) disruption of episodic memory in adulthood.
Differential metabolomic profiling of brain tissue revealed that these behavioural phenotypes were accompanied, most prominently, by alterations in specific lipid metabolism pathways. There is good evidence for a role of lipids in cognition in Alzheimers disease and ageing.
In this project we will investigate whether these changes in brain lipid metabolism might be important in generating the problems with memory and attention in adulthood in these and other mutant lines of mice. This investigates a much wider question about the role of lipids in cognition and whether lipids would provide a useful therapeutic target for diseases associated with a neurodevelopmental origin such as schizophrenia and autism.
5 recent publications related to project:
- O'Callaghan MJ, Bay-Richter C , O'Tuathaigh CMP, Heery DM, Waddington JL and Moran PM (2014) Dopamine D2 but not Dopamine D1 receptor is necessary for the enhancement of latent inhibition by clozapine and haloperidol in mice. Journal of Psychopharmacology 28(10) 973-7.
- Chan CM, Fulton J, Montiel-duarte C, Collins HM, Bharti N, Wadein F, Moran PM, Mongan NP and Heery DM (2013) A Signature Motif Mediating Selective Interactions of BCL11A with the NR2E/F Subfamily of Orphan Nuclear Receptors. Nucleic Acids Research 41 :9663-79.
- McIntosh AL, Ballard TM, Steward LJ, Moran PM and Fone KCF (2013). The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats. Psychopharmacology. 228 : 31-42.
- Bay-Richter C, O'Callaghan MJ, Mathur N, O'Tuathaigh CMP, Heery DM, Fone KCF, Waddington JL and Moran PM (2013) D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors. Neuropsychopharmacology, 38: 1512-1520.
- Rafter M, Fone KC and Moran PM, 2016. Glutamate Pharmacological models relevant to schizophrenia and psychosis: can a receptor occupancy normalisation approach reduce the gap between animal and human experiments?. In: MIKHAIL PLETNIKOV, ed., Modeling Psychopathogical dimensions of Schizophrenia: From molecules to Behaviour 23. Elsevier. 140-184