Fibrotic scar model and TGF-ß1 differently modulate action potential firing and voltage-dependent ion currents in hippocampal neurons in primary culture.
Eur J Neurosci
; 46(6): 2161-2176, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28833693
ABSTRACT
Traumatic injury of the central nervous system is accompanied by various functional and morphological changes. Animal models of traumatic brain injury are commonly used to investigate changes in behaviour, morphology, in the expression of various proteins around the site of the injury, or the expression of diagnostically important biomarkers. Excitability of a single neuron at, or close to, the site of injury was rarely investigated. Several in vitro models were developed which allow such investigation. In the present work, we employed a fibrotic scar model according to Kimura-Kuroda and coauthors to analyse altered excitability of rat hippocampal neurons under the conditions mimicking traumatic brain injury. Hippocampal neurons from newborn rats were cultured either on a fibrotic scar model or in the presence of TGF-ß1, a cytokine secreted at a brain injury site that may have both neuroprotective and neurodegenerative function. Fibrotic scar facilitated ability of neonatal hippocampal neurons to fire action potential series by increasing the density of voltage activated sodium and potassium currents. Chondroitin sulphate proteoglycans played substantial role in these effects, as proven by their full reversion after administration of Chondroitinase ABC. In contrast, TGF-ß1 did not contribute to them. An application of TGF-ß1 itself attenuated generation of action potentials, inhibited sodium current and potentiated potassium currents. Main alteration of electrophysiological parameters of neonatal hippocampal neurons caused by a fibrotic scar model is enhanced excitability. TGF-ß1 may have predominantly neuroprotective role in injured rat hippocampus.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
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Fator de Crescimento Transformador beta
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Hipocampo
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Eslováquia