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Dr George E. Barreto

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I am a Neuroscientist in the Department of Biological Sciences at the University of Limerick. My research has been focused on addressing the signalling pathways affected by hormonal deprivation in the brain. With aging, and especially during the menopause/andropause, hormonal levels in blood, and brain, are significantly decreased and this might be a causative factor for an increased susceptibility to develop a neurodegenerative event. The brain is a steroidogenic tissue, meaning that it synthesizes endogenous estradiol and possesses the enzymatic machinery to convert testosterone into estradiol. Reduced hormonal levels in the brain are also associated with a dysregulation in lipid metabolism, and this pathophysiology may account for an increased neuroinflammation in the brain of Alzheimer’s and Parkinson’s patients, and this response is dependent on the sex. More importantly, sex differences in glial cells have been also observed, and these cells might be as important as neurons for brain homeostasis. My research interests also include addressing neuroprotection by Selective Estrogen Receptors Modulators (SERMs), such as those used in clinics (Tamoxifen, Raloxifene, Ospemifene and Bazedozifene) and a drug used as HRT (Hormonal Replacement Therapy) by post-menopausal women (Tibolone, a Selective Tissue Estrogenic Activity Regulator).

My current projects focus on deciphering the neuropathological mechanisms induced by accumulation of lipids (palmitic acid) in human astrocytes from male and female donors. Our goal is to identify different mechanisms by which hormones can affect brain lipid metabolism and how lipids accumulation can induce neuroinflammation in absence of brain-synthesized estradiol. We use transcriptomics, proteomics and metabolomics data generated in our lab, and the most current molecular and cellular tools (cell cultures, genes/proteins silencing, fluorescence microscopy, proteins and RNA analysis, immunohistology etc).

Publications

Baez-Jurado E, Rincón-Benavides MA, Hidalgo-Lanussa O, Guio-Vega G, Ashraf GM, Sahebkar A, Echeverria V, Garcia-Segura LM, Barreto GE. Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells. Frontier in Neuroendocrinology 2019 Jan;52:44-64. DOI: 10.1016/j.yfrne.2018.09.001

Martin-Jiménez C, Gaitán-Vaca DM, Areiza N, Echeverria V, Ashraf GM, González J, Sahebkar A, Garcia-Segura LM, Barreto GE. Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury. Neuroendocrinology 2019;108(2):142-160. DOI: 10.1159/000495078

Jurado-Coronel JC, Cabezas R, Ávila Rodríguez MF, Echeverria V, García-Segura LM, Barreto GE. Sex differences in Parkinson's disease: Features on clinical symptoms, treatment outcome, sexual hormones and genetics. Frontiers in Neuroendocrinology 2018 Jul;50:18-30. DOI: 10.1016/j.yfrne.2017.09.002

Martin-Jiménez CA, García-Vega Á, Cabezas R, Aliev G, Echeverria V, González J, Barreto GE. Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases. Progress in Neurobiology 2017 Nov;158:45-68. DOI: 10.1016/j.pneurobio.2017.08.001

Acaz-Fonseca E, Avila-Rodriguez M, Garcia-Segura LM, Barreto GE. Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions. Progress in Neurobiology 2016 Sep;144:5-26. DOI: 10.1016/j.pneurobio.2016.06.002