Imperial College London

Emeritus ProfessorGlendaGillies

Faculty of MedicineDepartment of Brain Sciences

Emeritus Professor of Neuroendocrine Pharmacology
 
 
 
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Contact

 

+44 (0)20 7594 7050g.gillies

 
 
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Location

 

515Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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77 results found

Al-Zaid FS, Hurley MJ, Dexter DT, Gillies GEet al., 2023, Neuroprotective role for RORA in Parkinson's disease revealed by analysis of post-mortem brain and a dopaminergic cell line, NPJ PARKINSONS DISEASE, Vol: 9

Journal article

Gillies GE, Virdee K, Pienaar I, Al-Zaid F, Dalley JWet al., 2017, Enduring, Sexually Dimorphic Impact of In Utero Exposure to Elevated Levels of Glucocorticoids on Midbrain Dopaminergic Populations, BRAIN SCIENCES, Vol: 7

Journal article

Virdee K, Kentrop J, Jupp B, Venus B, Hensman D, McArthur S, Wilkinson J, Robbins TW, Gillies G, Dalley JWet al., 2016, Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory, Psychopharmacology, Vol: 233, Pages: 3751-3761, ISSN: 1432-2072

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.

Journal article

McArthur S, Pienaar IS, Siddiqi SM, Gillies GEet al., 2015, Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment., Brain Structure and Function, Vol: 221, Pages: 2459-2475, ISSN: 1863-2653

The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias.

Journal article

Gillies GE, Virdee K, Mcarthur S, Dalley JWet al., 2014, SEX-DEPENDENT DIVERSITY IN VENTRAL TEGMENTAL DOPAMINERGIC NEURONS AND DEVELOPMENTAL PROGRAMING: A MOLECULAR, CELLULAR AND BEHAVIORAL ANALYSIS, NEUROSCIENCE, Vol: 282, Pages: 69-85, ISSN: 0306-4522

Journal article

Gillies GE, Pienaar IS, Vohra S, Qamhawi Zet al., 2014, Sex differences in Parkinson's disease, FRONTIERS IN NEUROENDOCRINOLOGY, Vol: 35, Pages: 370-384, ISSN: 0091-3022

Journal article

Virdee K, McArthur S, Brischoux F, Caprioli D, Ungless MA, Robbins TW, Dalley JW, Gillies GEet al., 2013, Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons which Underpin Sexually Dimorphic Behavioral Resilience., Neuropsychopharmacology

Journal article

Gillies GE, 2012, Differential actions of estrogens in the male and female brain: a case for sex-specific medicines, Brain Aromatase, Estrogens and Behavior, Publisher: Oxford University Press, Pages: 253-278, ISBN: 9780199841196

Book chapter

McArthur S, Gillies GE, 2011, Peripheral vs. Central Sex Steroid Hormones in Experimental Parkinson's Disease., Front Endocrinol (Lausanne), Vol: 2

The nigrostriatal dopaminergic (NSDA) pathway degenerates in Parkinson's disease (PD), which occurs with approximately twice the incidence in men than women. Studies of the influence of systemic estrogens in females suggest sex hormones contribute to these differences. In this review we analyze the evidence revealing great complexity in the response of the healthy and injured NSDA system to hormonal influences, and emphasize the importance of centrally generated estrogens. At physiological levels, circulating estrogen (in females) or estrogen precursors (testosterone in males, aromatized to estrogen centrally) have negligible effects on dopaminergic neuron survival in experimental PD, but can modify striatal dopamine levels via actions on the activity or adaptive responses of surviving cells. However, these effects are sexually dimorphic. In females, estradiol promotes adaptive responses in the partially injured NSDA pathway, preserving striatal dopamine, whereas in males gonadal steroids and exogenous estradiol have a negligible or even suppressive effect, effectively exacerbating dopamine loss. On balance, the different effects of gonadal factors in males and females contribute to sex differences in experimental PD. Fundamental sex differences in brain organization, including the sexually dimorphic networks regulating NSDA activity are likely to underpin these responses. In contrast, estrogen generated locally appears to preserve striatal dopamine in both sexes. The available data therefore highlight the need to understand the biological basis of sex-specific responses of the NSDA system to peripheral hormones, so as to realize the potential for sex-specific, hormone-based therapies in PD. Furthermore, they suggest that targeting central steroid generation could be equally effective in preserving striatal dopamine in both sexes. Clarification of the relative roles of peripheral and central sex steroid hormones is thus an important challenge for future studies.

Journal article

McArthur S, Cristante E, Paterno M, Christian H, Roncaroli F, Gillies GE, Solito Eet al., 2010, Annexin A1: A Central Player in the Anti-Inflammatory and Neuroprotective Role of Microglia, JOURNAL OF IMMUNOLOGY, Vol: 185, Pages: 6317-6328, ISSN: 0022-1767

Journal article

Dexter D, Allen R, Gillies G, Buckingham Jet al., 2010, Stress is a Predisposing Factor for Parkinson's Disease in Males but Not Females, MOVEMENT DISORDERS, Vol: 25, Pages: S619-S619, ISSN: 0885-3185

Journal article

Gillies GE, McArthur S, 2010, Independent influences of sex steroids of systemic and central origin in a rat model of Parkinson's disease: A contribution to sex-specific neuroprotection by estrogens, HORMONES AND BEHAVIOR, Vol: 57, Pages: 23-34, ISSN: 0018-506X

Journal article

Gillies GE, McArthur S, 2010, Estrogen actions in the brain and the bases for differential actions in men and women: a case for sex-specific medicines, Pharmacological Reviews, Vol: 62, Pages: 155-198

Journal article

McArthur S, Robinson IC, Gillies GE, 2010, Novel Ontogenetic Patterns of Sexual Differentiation in Arcuate Nucleus GHRH Neurons revealed in GHRH-Enhanced Green Fluorescent Protein Transgenic Mice, Endocrinology

Journal article

McArthur S, Prasongchean W, Gillies G, Solito Eet al., 2008, A critical role for the anti-inflammatory protein annexin A1 in microglial phagocytosis, FUNDAMENTAL & CLINICAL PHARMACOLOGY, Vol: 22, Pages: 23-23, ISSN: 0767-3981

Journal article

Solito E, McArthur S, Christian H, Gavins F, Buckingham JC, Gillies GEet al., 2008, Annexin A1 in the brain-undiscovered roles?, TRENDS IN PHARMACOLOGICAL SCIENCES, Vol: 29, Pages: 135-142, ISSN: 0165-6147

Journal article

McArthur S, McHale E, Gillies GE, 2007, The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner, NEUROPSYCHOPHARMACOLOGY, Vol: 32, Pages: 1462-1476, ISSN: 0893-133X

Journal article

McArthur S, Murray HE, Dhankot A, Dexter DT, Gillies GEet al., 2007, Striatal susceptibility to a dopaminergic neurotoxin is independent of sex hormone effects on cell survival and DAT expression but is exacerbated by central aromatase inhibition, JOURNAL OF NEUROCHEMISTRY, Vol: 100, Pages: 678-692, ISSN: 0022-3042

Journal article

Warne JP, John CD, Christian HC, Morris JF, Flower RJ, Sugden D, Solito E, Gillies GE, Buckingham JCet al., 2006, Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 291, Pages: E1264-E1273, ISSN: 0193-1849

Journal article

Gillies G, McArthur S, McHale E, 2006, Sex dimorphisms in the 3D cytoarchitecture of the adult VTA and permanent alterations by glucocorticoid exposure in late gestation, 6th International Congress of Neuroendocrinology, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: 95-96, ISSN: 0091-3022

Conference paper

McArthur S, Siddique ZL, Christian HC, Capone G, Theogaraj E, John CD, Smith SF, Morris JF, Buckingham JC, Gillies GEet al., 2006, Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats, ENDOCRINOLOGY, Vol: 147, Pages: 1904-1915, ISSN: 0013-7227

Journal article

McArthur S, McHale E, Dalley JW, Buckingham JC, Gillies GEet al., 2005, Atered mesencephalic dopaminergic populations in adulthood as a consequence of brief perinatal glucocorticoid exposure, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 17, Pages: 475-482, ISSN: 0953-8194

Journal article

Gillies GE, Murray HE, Dexter D, McArthur Set al., 2004, Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of Parkinson's disease, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, Vol: 78, Pages: 513-522, ISSN: 0091-3057

Journal article

Datla KP, Murray HE, Pillai AV, Gillies GE, Dexter DTet al., 2003, Differences in dopaminergic neuroprotective effects of estrogen during estrous cycle, NEUROREPORT, Vol: 14, Pages: 47-50, ISSN: 0959-4965

Journal article

Murray HE, Pillai AV, McArthur SR, Razvi N, Datla KP, Dexter DT, Gillies GEet al., 2003, Dose- and sex-dependent effects of the neurotoxin 6-hydroxydopamine on the nigrostriatal dopaminergic pathway of adult rats: Differential actions of estrogen in males and females, NEUROSCIENCE, Vol: 116, Pages: 213-222, ISSN: 0306-4522

Journal article

Pannell C, Simonian SX, Gillies GE, Luscher B, Herbison AEet al., 2002, Hypothalamic somatostatin and growth hormone-releasing hormone mRNA expression depend upon GABA<sub>A</sub> receptor expression in the developing mouse, NEUROENDOCRINOLOGY, Vol: 76, Pages: 93-98, ISSN: 0028-3835

Journal article

Gillies G, Murray H, Dexter D, 2002, Organizational and activational effects of sex steroid hormones in the brain: Implications for growth, neuroprotection and disease susceptibility, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

Journal article

Lamfon H, Gillies G, Theogaraj E, John C, Smith SF, Buckingham JCet al., 2002, Effects of neonatal dexamethasone, treatment on thymic NOS-2 expression in the adult rat, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

Journal article

Murray HE, McArthur SR, Dexter DT, Gillies GEet al., 2002, Sex difference in the effects of 6-hydroxydopamine lesions in the nigrostriatal dopaminergic pathway of adult rats and sexually dimorphic actions of 17 β-estradiol., BRITISH JOURNAL OF PHARMACOLOGY, Vol: 135, ISSN: 0007-1188

Journal article

Murray HE, Rantle CM, Gillies GE, 2000, Differential ontogeny and sexual dimorphism of γ-aminobutyric acid content and secretion in selected nuclei of the rat hypothalamus, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 525, Pages: 54P-55P, ISSN: 0022-3751

Journal article

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