The role of neurosteroids in the pathogenesis of hepatic encephalopathy
Hepatic Encephalopathy (HE) represents a neuropsychiatric syndrome caused by acute or chronic liver failure. Hyperammonemia plays a pivotal role in the development of HE through modulation of neurotransmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, and energy deficit. Neuro...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
University of Belgrade, Medical Faculty
2016-01-01
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| Series: | Medicinski Podmladak |
| Subjects: | |
| Online Access: | http://scindeks-clanci.ceon.rs/data/pdf/0369-1527/2016/0369-15271601035M.pdf |
| Summary: | Hepatic Encephalopathy (HE) represents a neuropsychiatric syndrome caused by acute or chronic liver failure. Hyperammonemia plays a pivotal role in the development of HE through modulation of neurotransmission, oxidative stress, neuroinflammation, mitochondrial dysfunction, and energy deficit. Neurosteroids contribute significantly to increased GABAergic tone in HE. Ammonia, in combination with manganese and proinflammatory cytokines, stimulate neurosteroid synthesis by up-regulation of translocator protein, a component of multiprotein complex that stimulate cholesterol transport into astrocytic mitochondria. Cholesterol serves as a substrate for the synthesis of neurosteroids allopregnanolone and tetrahydro-deoxycorticosterone. After release from astrocytes, allopregnanolone and tetrahydro-deoxycorticosterone potentiate GABAergic transmission by positive allosteric modulation of GABAA receptor, thus contributing to cognitive deficit and alterations in sleep-wake cycle. Additional potential mechanisms of neurosteroid action in HE include modulation of serotoninergic, cholinergic, glutamatergic, glycinergic, and opioid receptor activities, as well as modulation of gene expression. This review aimed to summarize current knowledge of the role of neurosteroids in the pathogenesis of HE. |
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| ISSN: | 0369-1527 2466-5525 |