Downregulation of connexin 43 potentiates amitriptyline-induced brain-derived neurotrophic factor expression in primary astrocytes through lysophosphatidic acid receptor1/3, Src, and extracellular signal-regulated kinase.
Eur J Pharmacol
; 925: 174986, 2022 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-35490723
ABSTRACT
Connexin 43 (Cx43) expression is decreased in the prefrontal cortex of patients with depression, but its significance is still unknown. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are involved in the effects of antidepressant. However, the relationship between Cx43 expression and induction of brain-derived neurotrophic factor production by antidepressants is unknown. On the basis of our previous study, which showed that adrenergic receptors stimulation results in potentiation of BDNF expression in astrocytes with downregulated Cx43 expression, we investigated the induction of BDNF expression by amitriptyline, a tricyclic antidepressant, in Cx43-knockdown astrocytes. Amitriptyline treatment potentiated BDNF expression in Cx43-knockdown astrocytes compared with those treated with non-targeting small interfering RNA (siRNA). Using a pharmacological approach, we revealed that the potentiating effect of amitriptyline on BDNF expression was mediated by lysophosphatidic acid (LPA) receptor1/3 (LPA1/3) stimulation and subsequent activation of Src-extracellular signal-regulated kinase (ERK) signaling. These findings suggest that downregulation of Cx43 in patients with depression might contribute to the therapeutic efficacy of antidepressants rather than the pathogenesis of depression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Astrocitos
/
Conexina 43
/
Factor Neurotrófico Derivado del Encéfalo
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Amitriptilina
Límite:
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón