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Effects of PDE4B inhibition on excessive weight gain-induced impairment in cognitive function in laboratory mice

   Faculty of Biological Sciences

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  Dr S Clapcote, Dr J. Johnston  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

In humans, obesity impairs cognition and produces atrophy of brain regions associated with learning and memory. Individual cognitive performance declines with increases in body mass and energy consumption. These deficits can be observed throughout life, from childhood to late adulthood. Our lab has generated mice that have a catalytic mutant form of PDE4B (Y358C) with a decreased ability to hydrolyse cAMP. We previously found that these mice show enhanced learning and memory; enhanced long-term potentiation and less synaptic depression in hippocampal slices; increased dendritic spine density in the hippocampus and amygdala; and enhanced neurogenesis in the adult dentate gyrus (McGirr et al. 2016 Neuropsychopharmacology 41:1080-92). In this PhD project, you will explore the cellular and biochemical mechanisms that might underlie obesity-induced changes in brain volume and cognitive function. Specifically, you will use behavioural, electrophysiological, biochemical and histological techniques to investigate the effects of high-fat diet-induced obesity on cognitive function in wild-type mice compared with mice with the PDE4B¬Y358C mutation that was previously shown to cause cognitive enhancement in lean mice fed a standard rodent diet. These experiments will increase understanding of the cellular processes underlying cognitive decline in obesity and the effects of inhibition of PDE4B upon this phenomenon

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.


McGirr A, Lipina TV, Mun HS, Georgiou J, Al-Amri AH, Ng E, Zhai D, Elliott C, Cameron RT, Mullins JG, Liu F, Baillie GS, Clapcote SJ, Roder JC. Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition. Neuropsychopharmacology. 2016 Mar;41(4):1080-92. doi: 10.1038/npp.2015.240.

Titus DJ, Wilson NM, Freund JE, Carballosa MM, Sikah KE, Furones C, Dietrich WD, Gurney ME, Atkins CM. Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor. J Neurosci. 2016 Jul 6;36(27):7095-108. doi: 10.1523/JNEUROSCI.3212-15.2016.

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