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9th Edition of International Conference on

Neurology and Neurological Disorders

June 20-22, 2024 | Paris, France

Neurology 2022

Torbjorn Backstrom

Speaker at Neurology and Neurological Disorders 2022 - Torbjorn Backstrom
Umea Neurosteroid Research Center, Sweden
Title : GABA-A receptor modulating steroids impair learning and memory but can be antagonized with GABA-A receptor modulating steroid antagonists.

Abstract:

Gamma-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the brain and GABA-ergic transmission is shown to be of importance for regulation of mood, memory, and food intake. The progesterone metabolite allopregnanolone (Allo) is a positive GABAA receptor modulating steroid with potent effects. In humans, disorders like premenstrual dysphoric disorder (PMDD), hepatic encephalopathy and polycystic ovarian syndrome are associated with elevated Allo levels and increased negative mood, disturbed memory, and increased food intake in some individuals. This is surprising as Allo shares many properties with benzodiazepines and is mainly considered to be anxiolytic and anti-depressant. However, it is well established that in certain individuals GABAA receptor active compounds could have paradoxical effects and thus be anxiogenic in low physiological plasma concentrations while anxiolytic at high levels. In Alzheimer transgenic mice continuous allo in low stress concentrations deteriorated the dementia progress. We have demonstrated that isoallopregnanolone (Isoallo), the 3β-OH sibling of Allo, functions as a GABAA receptor modulating steroid antagonist (GAMSA), but without any effects by its own on the GABAA receptors. The antagonistic effect is noted in most GABAA subtypes investigated so far. In vivo, Isoallo inhibits Allo-induced anesthesia in rats, as well as sedation or saccadic eye velocity in humans. Isoallo has been studied in women with PMDD. In two phase II studies, Isoallo (Sepranolone) injections significantly ameliorated negative mood in women with PMDD compared with placebo. One GAMSA, UC1011, could inhibit Allo induced memory disturbances in rats. A GAMSA for oral administration have also been developed, GR3027, has been shown to restore learning and motor coordination in rats with hepatic encephalopathy. In human’s, vigilance, cognition, and pathological EEG was improved in patients with hepatic encephalopathy when treated with GR3027.

 

Biography:

Torbjorn C Backstrom currently works at the Clinical sciences, Umea Neurosteroid Research Center, Norrlands universitetssjukhus. Torbjorn does research in Neurology, Gynaecology and Obstetrics. Their current project is 'Satiety induction in polycystic ovarian syndrome and Prader Willi syndrome'.

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