Joyce Yau
Senior Lecturer, FHEA
Address
- Street
-
The Queen's Medical Research Institute
BioQuarter
47 Little France Crescent - City
- Edinburgh
- Post code
- EH16 4TJ
Undergraduate teaching
Honours Biomedical Sciences
• Course Organiser - “Genetics and Environmental Influences on Behaviour and Mental Health”
• Contributing lecturer – “Endocrine Physiology and Pharmacology”
Postgraduate teaching
Contributing lecturer - Wellcome Trust Translational Neuroscience 4-year PhD, block 3 Disorders of older age.
Supervisor - PhD and MSc by research students
Open to PhD supervision enquiries?
Yes
Research summary
My research focuses on understanding how stress regulates brain ageing and cognitive function in health and disease. The goal is to uncover mechanisms that lead to new targets for the treatment of cognitive impairment associated with ageing and stress-related disorders.
Key words: Brain, ageing, stress, diet, memory, anxiety, behaviours, cognitive impairment, glucocorticoids, dementia, depression.
Cognitive impairment in the absence of neuropathology occurs in a substantial segment of the elderly population. The mechanisms that underlie mild cognitive impairment (MCI), which may precede dementia, are not fully understood. Risk factors include age, genetics and other health conditions such as diabetes, obesity, and depression. One environmental factor linked to MCI of particular interest is increased exposure to stress glucocorticoid (GC) hormones over the lifespan.
Brain GCs and cognitive function
Whereas only ~5% of circulating GCs are free to enter tissues, intracellular steroid metabolising enzymes make a significant contribution to the local pool of biologically active GCs. We have discovered that 11beta-HSD1, an enzyme that generates active GCs within specific target tissues including in the brain, directly contributes to age-related cognitive decline. Among our key findings, a deficiency of 11beta-HSD1 in a transgenic mouse model protects against impaired memory in old age; and pharmacological inhibition of the enzyme reverses the age-related memory deficits. This supports 11beta-HSD1 as a novel therapeutic target for cognitive enhancement. To help translate our preclinical work to humans, Professor Scott Webster developed a CNS-active selective 11beta-HSD1 inhibitor (Xanamem) which is currently in phase 2 clinical trials for Alzheimer’s disease (Actinogen Medical).
Midlife stress and brain ageing
In contrast to healthy young adults, recovery from chronic stress effects on the brain may be less reversible from midlife to old age. In our preclinical models, we have found that stress exposure in middle-age caused memory impairments that lasted at least 6 months after stress cessation. Strikingly, a deficiency of 11beta-HSD1 prevents the midlife stress triggered impairment of memory into early old age. Unravelling the mechanisms that underpin such long-term impairing effects on cognition may reveal new therapeutic targets.