Nicotine-mediated neuroprotection of rat spinal networks against excitotoxicity.
Eur J Neurosci
; 47(11): 1353-1374, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29770521
ABSTRACT
Activation of neuronal nicotinic acetylcholine receptors (nAChRs) by nicotine is reported to protect brain neurons from glutamate excitotoxicity. We inquired whether a similar phenomenon can occur in the rat isolated spinal cord (or spinal slice culture) challenged by a transient (1 hr) application of kainate (a powerful glutamate receptor agonist) to induce excitotoxicity mimicking spinal injury in vitro. We recorded spinal reflexes and fictive locomotion generated by the locomotor central pattern generator before and 24 hr after applying kainate. We also monitored network activity with Ca2+ imaging and counted neurons and glia with immunohistochemical methods. In control conditions, nicotine (1 µM; 4 hr) depressed reflexes and fictive locomotion with slow recovery and no apparent neurotoxicity at 24 hr although synchronous Ca2+ transients appeared in slice cultures. Kainate nearly halved neuron numbers (while sparing glia), decreased reflexes and Ca2+ transients, and suppressed fictive locomotion. When nicotine was applied (4 hr) after washout of kainate, fictive locomotor cycles appeared 24 hr later though with low periodicity, and significant protection of neurons, including motoneurons, was observed. Nicotine applied together with kainate and maintained for further 4 hr yielded better neuroprotection, improved fictive locomotion expression and reversed the depression of Ca2+ transients. nAChR antagonists did not intensify kainate neurotoxicity and inhibited the neuroprotective effects of nicotine. These data suggest that nicotine was efficacious to limit histological and functional excitotoxic damage probably because it activated and then desensitized nAChRs on excitatory and inhibitory network neurons to prevent triggering intracellular cell death pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reflexo
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Medula Espinal
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Traumatismos da Coluna Vertebral
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Agonistas Nicotínicos
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Fármacos Neuroprotetores
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Agonistas de Aminoácidos Excitatórios
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Geradores de Padrão Central
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Neurônios Motores
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Nicotina
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália