GABA-A receptor modulating steroids in acute and chronic stress; relevance for cognition and dementia?
| Autor: | Ming-De Wang, Torbjörn Bäckström, Maja Johansson, Roberta Diaz Brinton, Ronald W. Irwin, J. Sjöstedt, Sara K. Bengtsson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Neurology
Neurologi Physiology Disease Bioinformatics Allopregnanolone Biochemistry lcsh:RC346-429 chemistry.chemical_compound 0302 clinical medicine Endocrinology GABA-A receptor modulating steroids Chronic stress 0303 health sciences education.field_of_study GABAA receptor lcsh:QP351-495 Cognition 3. Good health psychological phenomena and processes Neurovetenskaper medicine.medical_specialty Population education Article lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Memory mental disorders medicine Dementia Learning lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Molecular Biology lcsh:Neurology. Diseases of the nervous system 030304 developmental biology GABA-A receptor modulating steroid antagonists Endocrine and Autonomic Systems business.industry Neurosciences medicine.disease lcsh:Neurophysiology and neuropsychology chemistry business 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Stress Neurobiology of Stress, Vol 12, Iss, Pp-(2020) |
| ISSN: | 2352-2895 |
| Popis: | Cognitive dysfunction, dementia and Alzheimer's disease (AD) are increasing as the population worldwide ages. Therapeutics for these conditions is an unmet need. This review focuses on the role of the positive GABA-A receptor modulating steroid allopregnanolone (APα), it's role in underlying mechanisms for impaired cognition and of AD, and to determine options for therapy of AD. On one hand, APα given intermittently promotes neurogenesis, decreases AD-related pathology and improves cognition. On the other, continuous exposure of APα impairs cognition and deteriorates AD pathology. The disparity between these two outcomes led our groups to analyze the mechanisms underlying the difference. We conclude that the effects of APα depend on administration pattern and that chronic slightly increased APα exposure is harmful to cognitive function and worsens AD pathology whereas single administrations with longer intervals improve cognition and decrease AD pathology. These collaborative assessments provide insights for the therapeutic development of APα and APα antagonists for AD and provide a model for cross laboratory collaborations aimed at generating translatable data for human clinical trials. Highlights • Continuous increased allopregnanolone deteriorates memory and accelerates disease progression in tg-Alzheimer’s mice. • Intermittent allopregnanolone treatment improves memory and prevents disease progression in tg-Alzheimer’s mice. • Treatments with intermittent GABA-A modulating steroid antagonists and allopregnanolone are suggested in the paper. |
| Databáze: | OpenAIRE |
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