Serotonin stimulates mitochondrial transport in hippocampal neurons.
Mol Cell Neurosci
; 36(4): 472-83, 2007 Dec.
Article
en En
| MEDLINE
| ID: mdl-17904380
ABSTRACT
Axonal transport of mitochondria is critical for proper neuronal function. However, little is known about the extracellular signals that regulate this process. In the present study, we show that the neuromodulator serotonin (5-HT) greatly enhances mitochondrial movement in the axons of rat hippocampal neurons in vitro. Administration of a 5-HT1A receptor antagonist inhibited mitochondrial movement, whereas addition of fluoxetine, a selective serotonin reuptake inhibitor, promoted mitochondrial movement. 5-HT receptors are known to activate the Akt/Protein kinase B pathway. Consistent with this, directional mitochondrial movement was almost completely blocked by a specific Akt inhibitor. Moreover, an inhibitor of glycogen synthase kinase-3beta (GSK3beta), a kinase whose activity is blocked by Akt-mediated phosphorylation, promoted mitochondrial movement. These findings show that 5-HT1A receptor activation stimulates mitochondrial movement in hippocampal neurons by inhibiting GSK3beta activity via Akt. Our findings suggest that 5-HT may mediate the redistribution of energy sources within responsive neurons, a possibility that has significant implications for understanding the global biological effects of this important neuromodulator.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Axones
/
Transporte Axonal
/
Transducción de Señal
/
Serotonina
/
Hipocampo
/
Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos