Endothelial cells promote excitatory synaptogenesis and improve ischemia-induced motor deficits in neonatal mice.
Neurobiol Dis
; 121: 230-239, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30308244
ABSTRACT
Brain microvascular endothelial cells (BMEC) are highly complex regulatory cells that communicate with other cells in the neurovascular unit. Cerebral ischemic injury is known to produce detectable synaptic dysfunction. This study aims to investigate whether endothelial cells in the brain regulate postnatal synaptic development and to elucidate their role in functional recovery after ischemia. Here, we found that in vivo engraftment of endothelial cells increased synaptic puncta and excitatory postsynaptic currents in layers 2/3 of the motor cortex. This pro-synaptogenic effect was blocked by the depletion of VEGF in the grafted BMEC. The in vitro results showed that BMEC conditioned medium enhanced spine and synapse formation but conditioned medium without VEGF had no such effects. Moreover, under pathological conditions, transplanted endothelial cells were capable of enhancing angiogenesis and synaptogenesis and improved motor function in the ischemic injury model. Collectively, our findings suggest that endothelial cells promote excitatory synaptogenesis via the paracrine factor VEGF during postnatal development and exert repair functions in hypoxia-ischemic neonatal mice. This study highlights the importance of the endothelium-neuron interaction not only in regulating neuronal development but also in maintaining healthy brain function.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Isquemia Encefálica
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Potenciais Pós-Sinápticos Excitadores
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Células Endoteliais
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Transtornos Motores
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Córtex Motor
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article