Schuele, Cornelius and Nothdurfter, Caroline and Rupprecht, Rainer (2014) The role of allopregnanolone in depression and anxiety. PROGRESS IN NEUROBIOLOGY, 113. pp. 79-87. ISSN 0301-0082, 1873-5118
Full text not available from this repository. (Request a copy)Abstract
Neuroactive steroids such as allopregnanolone do not only act as transcriptional factors in the regulation of gene expression after intracellular back-oxidation into the 5-alpha pregnane steroids but may also alter neuronal excitability through interactions with specific neurotransmitter receptors. In particular, certain 3 alpha-reduced metabolites of progesterone such as 3 alpha,5 alpha-tetrahydroprogesterone (allopregnanolone) and 3 alpha,5 beta-tetrahydroprogesterone (pregnanolone) are potent positive allosteric modulators of the GABA(A) receptor complex. During the last years, the downregulation of neurosteroid biosynthesis has been intensively discussed to be a possible contributor to the development of anxiety and depressive disorder. Reduced levels of allopregnanolone in the peripheral blood or cerebrospinal fluid were found to be associated with major depression, anxiety disorders, premenstrual dysphoric disorder, negative symptoms in schizophrenia, or impulsive aggression. The importance of allopregnanolone for the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but probably also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function. Certain pharmacokinetic obstacles limit the therapeutic use of natural neurosteroids (low bioavailability, oxidation to the ketone). Until now synthetic neuroactive steroids could not be established in the treatment of anxiety disorders or depression. However, the translocator protein (18 kDa) (TSPO) which is important for neurosteroidogenesis has been identified as a potential novel target. TSPO ligands such as XBD 173 increase neurosteroidogenesis and have anxiolytic effects with a favorable side effect profile. (c) 2013 Published by Elsevier Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GABA-A RECEPTOR; NEUROACTIVE STEROID COMPOSITION; POSTTRAUMATIC-STRESS-DISORDER; OLFACTORY-BULBECTOMIZED RAT; VENTRAL TEGMENTAL AREA; PROTEIN 18 KDA; SOCIAL-ISOLATION; MAJOR DEPRESSION; PLASMA-CONCENTRATIONS; PANIC DISORDER; Allopregnanolone; Neuroactive steroids; Depression; Anxiety; Affective disorders |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 21 Jul 2020 08:55 |
| Last Modified: | 21 Jul 2020 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10746 |
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