The role of allopregnanolone in depressive-like behaviors: Focus on neurotrophic proteins
| Autor: | Maurício Schüler Nin, Felipe Borges Almeida, Helena Maria Tannhauser Barros |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Physiology
HSD hydroxysteroid dehydrogenase Hippocampus CSF cerebrospinal fluid Biochemistry lcsh:RC346-429 FST forced swim test chemistry.chemical_compound 0302 clinical medicine Endocrinology Neurotrophic factors Neurosteroid Medicine TSPO 18 kDa translocator protein Brexanolone Selective brain steroidogenic stimulant biology Depression lcsh:QP351-495 Neurogenesis PXR pregnane xenobiotic receptor Articles from the Special Issue on Allopregnanolone role in the neurobiology of stress and mood disorders Edited by Graziano Pinna PTSD post-traumatic stress disorder BDNF brain-derived neurotrophic factor USV ultrasonic vocalization Neurotrophin CUS chronic unpredictable stress TrkB tropomyosin receptor kinase B Neuroactive steroid NGF nerve growth factor SBSS selective brain steroidogenic stimulant lcsh:RC321-571 THP tetrahydroprogesterone EKR extracellular signal-regulated kinase 03 medical and health sciences Cellular and Molecular Neuroscience Animal models of depression lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Molecular Biology lcsh:Neurology. Diseases of the nervous system SSRI selective serotonin reuptake inhibitor Endocrine and Autonomic Systems business.industry Allopregnanolone GABAAR GABA type A receptor 3α 5α-tetrahydroprogesterone 030227 psychiatry lcsh:Neurophysiology and neuropsychology BDNF chemistry biology.protein business GABA γ-aminobutyric acid Neuroscience 030217 neurology & neurosurgery Behavioural despair test |
| Zdroj: | Neurobiology of Stress Neurobiology of Stress, Vol 12, Iss, Pp-(2020) |
| ISSN: | 2352-2895 |
| DOI: | 10.1016/j.ynstr.2020.100218 |
| Popis: | Allopregnanolone (3α,5α-tetrahydroprogesterone; pharmaceutical formulation: brexanolone) is a neurosteroid that has recently been approved for the treatment of postpartum depression, promising to fill part of a long-lasting gap in the effectiveness of pharmacotherapies for depressive disorders. In this review, we explore the experimental research that characterized the antidepressant-like effects of allopregnanolone, with a particular focus on the neurotrophic adaptations induced by this neurosteroid in preclinical studies. We demonstrate that there is a consistent decrease in allopregnanolone levels in limbic brain areas in rodents submitted to stress-induced models of depression, such as social isolation and chronic unpredictable stress. Further, both the drug-induced upregulation of allopregnanolone or its direct administration reduce depressive-like behaviors in models such as the forced swim test. The main drugs of interest that upregulate allopregnanolone levels are selective serotonin reuptake inhibitors (SSRIs), which present the neurosteroidogenic property even in lower, non-SSRI doses. Finally, we explore how these antidepressant-like behaviors are related to neurogenesis, particularly in the hippocampus. The protagonist in this mechanism is likely the brain-derived neurotrophic factor (BFNF), which is decreased in animal models of depression and may be restored by the normalization of allopregnanolone levels. The role of an interaction between GABA and the neurotrophic mechanisms needs to be further investigated. |
| Databáze: | OpenAIRE |
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