Functional modulation of strychnine-sensitive glycine receptors in rat hippocampal pyramidal neurons by amyloid-ß protein (1-42).
Brain Res
; 1651: 61-72, 2016 11 15.
Article
em En
| MEDLINE
| ID: mdl-27663971
ABSTRACT
Amyloid-ß peptide (Aß) is considered a key protein in the pathogenesis of Alzheimer's disease because of its neurotoxicity, resulting in impaired synaptic function and memory. On the other hand, it was demonstrated that low (picomolar) concentrations of Aß enhance synaptic plasticity and memory, suggesting that in the healthy brain, physiological Aß concentrations are necessary for normal cognitive functions. In the present study, we found that Aß (1-42) in concentrations of 10 pÐ - 100nÐ enhanced desensitization of the glycine-activated current in isolated CA3 pyramidal neurons and also reversibly suppressed its peak amplitude during short (600ms) co-application with agonist. The effect was most prominent at low glycine concentrations. When glycine receptors were activated by other receptor agonists - taurine and ß-alanine, the changes of current kinetics and amplitudes induced by Aß had a similar character. When Aß (100 pM) was added to the bath solution, it caused, besides acceleration of desensitization, more pronounced reduction of peak current amplitude. This effect developed slowly, during a few minutes, and was more prominent at saturating concentrations of agonists. The results suggest that Aß interacts with glycine receptors through three different mechanisms - by enhancing receptor desensitization, by rapid inhibition of the receptor, and also by means of a slowly developing inhibition of the amplitude of the current, possibly through intracellular mechanisms. The observed changes in the activity of glycine receptors induced by Aß can lead to suppression of the tonic inhibition of hippocampal neurons mediated by extrasynaptic glycine receptors.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeos beta-Amiloides
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Receptores de Glicina
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Células Piramidais
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Região CA3 Hipocampal
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2016
Tipo de documento:
Article