Megan Holmes
Personal Chair of Molecular Neurodenocrinology

Address
- Street
-
Queens Medical Research Institute
Edinburgh Bioquarter
47 Little France Crescent - City
- Edinburgh
- Post code
- EH16 4TJ
Current research interests
The hormonal response to stress is crucial for survival, yet chronic stress can lead to increased susceptibility to both cardiometabolic disease, as well as psychiatric and memory disorders. My research has focussed on the regulation of the normal response to stress through the hypothalamo-pituitary adrenal axis (Good Stress) and how this is can become dysregulated to cause disease (Bad Stress). My main focus has been on the effect of stress or high glucocorticoids (cortisol in man or cortisosterone in rodents, as well as synthetic steroids such as dexamethasone) during vulnerable developmental periods (prenatal or postnatal) to ‘programme’ life-long changes in affective behaviour and memory and understand the mechanisms that underpin these effects. Such mechanistic studies allow development of novel therapies to alleviate or reverse the adverse consequences of the stress hormones. Other interests include the underestimated importance of the brain in the regulation of blood pressure and salt appetite, and the consequences of stress particularly in development on the trajectory of cognitive decline with age. A major component of our work involves the use of targeted rodent models, that have been developed in our laboratory. We also have developed state-of-the–art high resolution, in vivo imaging paradigms to provide non invasive functional imaging of behavioural responding animals using functional Magnetic Resonance Imaging (fMRI) and monitor feto-placental development (particularly of umbilical vessels and fetal heart) by high resolution ultrasound.-
High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
In:
Cardiovascular Research
DOI: https://doi.org/10.1093/cvr/cvac160
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress
In:
Epigenetics and Chromatin
DOI: https://doi.org/10.1186/s13072-021-00405-8
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Vortioxetine ameliorates anhedonic-like behaviour and promotes strategic cognitive performance in a rodent touchscreen task
In:
Scientific Reports
DOI: https://doi.org/10.1038/s41598-021-88462-7
Research output: Contribution to Journal › Article (E-pub ahead of print) -
THE ROLE OF 11ß-HYDROXY STEROID DEHYDROGENASE TYPE 2 IN GLUCOCORTICOID PROGRAMMING OF AFFECTIVE AND COGNITIVE BEHAVIOURS
In:
Neuroendocrinology
DOI: https://doi.org/10.1159/000499660
Research output: Contribution to Journal › Review article (E-pub ahead of print) -
BDNF+/- rats exhibit depressive phenotype and altered expression of genes relevant in mood disorders
In:
Genes, Brain and Behavior, vol. 18
DOI: https://doi.org/10.1111/gbb.12546
Research output: Contribution to Journal › Article (Published) -
Resilient and depressive-like rats show distinct cognitive impairments in the touchscreen paired-associates learning (PAL) task
In:
Neurobiology of Learning and Memory, vol. 155, pp. 287-296
DOI: https://doi.org/10.1016/j.nlm.2018.08.014
Research output: Contribution to Journal › Article (Published) -
The effect of rat strain and stress exposure on performance in touchscreen tasks
(8 pages)
In:
Physiology & Behavior, vol. 184, pp. 83-90
DOI: https://doi.org/10.1016/j.physbeh.2017.11.010
Research output: Contribution to Journal › Article (Published) -
11β-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation
In:
Brain, Behavior, and Immunity
DOI: https://doi.org/10.1016/j.bbi.2017.11.015
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Viscosity and haemodynamics in a late gestation rat feto-placental arterial network
In:
Biomechanics and Modeling in Mechanobiology
DOI: https://doi.org/10.1007/s10237-017-0892-8
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Forebrain-specific transgene rescue of 11β-HSD1 associates with impaired spatial memory and reduced hippocampal BDNF mRNA levels in aged 11β-HSD1 deficient mice
In:
Journal of Neuroendocrinology
DOI: https://doi.org/10.1111/jne.12447
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity
In:
Seminars in Immunopathology, pp. 1-25
DOI: https://doi.org/10.1007/s00281-016-0575-z
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess
(6 pages)
In:
Proceedings of the National Academy of Sciences (PNAS), vol. 113, pp. 6265-70
DOI: https://doi.org/10.1073/pnas.1520356113
Research output: Contribution to Journal › Article (Published) -
Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension
(11 pages)
In:
Circulation, vol. 133, pp. 1360-1370
DOI: https://doi.org/10.1161/CIRCULATIONAHA.115.019341
Research output: Contribution to Journal › Article (Published) -
The role of Brain Derived Neurotrophic Factor in learned fear processing: an awake rat fMRI study
In:
Genes, Brain and Behavior
DOI: https://doi.org/10.1111/gbb.12277
Research output: Contribution to Journal › Article (Published) -
High-fat diet during pregnancy acts as a stressor increasing maternal glucocorticoids' signaling to the fetus and disrupting maternal behavior in a mouse model
In:
Psychoneuroendocrinology, vol. 61, pp. 10
DOI: https://doi.org/10.1016/j.psyneuen.2015.07.414
Research output: Contribution to Journal › Meeting abstract (Published) -
Fetal programming of adult behaviour by stress and glucocorticoids
In:
Psychoneuroendocrinology, vol. 61, pp. 9
DOI: https://doi.org/10.1016/j.psyneuen.2015.07.411
Research output: Contribution to Journal › Meeting abstract (Published) -
Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids' signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice
(13 pages)
In:
Psychoneuroendocrinology, vol. 60, pp. 138-150
DOI: https://doi.org/10.1016/j.psyneuen.2015.06.012
Research output: Contribution to Journal › Article (Published) -
Imaging learned fear circuitry in awake mice using fMRI
(10 pages)
In:
European Journal of Neuroscience, vol. 42, pp. 2125-2134
DOI: https://doi.org/10.1111/ejn.12939
Research output: Contribution to Journal › Article (Published) -
Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice
(12 pages)
In:
Psychoneuroendocrinology, vol. 59, pp. 59–70
DOI: https://doi.org/10.1016/j.psyneuen.2015.05.003
Research output: Contribution to Journal › Article (Published) -
Early Life Stress Produces Compulsive-Like, but Not Impulsive, Behavior in Females
(9 pages)
In:
Behavioral Neuroscience, vol. 129, pp. 300-308
DOI: https://doi.org/10.1037/bne0000059
Research output: Contribution to Journal › Article (Published)