Transient Receptor Potential Melastatin 3 Is Functionally Expressed in Oligodendrocyte Precursor Cells and Is Upregulated in Ischemic Demyelinated Lesions.
Biol Pharm Bull
; 44(2): 181-187, 2021.
Article
en En
| MEDLINE
| ID: mdl-33518671
Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into oligodendrocytes and myelinate axons. The number of OPCs is reportedly increased in brain lesions in some demyelinating diseases and during ischemia; however, these cells also secrete cytokines and elicit both protective and deleterious effects in response to brain injury. The mechanism regulating the behaviors of OPCs in physiological and pathological conditions must be elucidated to control these cells and to treat demyelinating diseases. Here, we focused on transient receptor potential melastatin 3 (TRPM3), a Ca2+-permeable channel that is activated by the neurosteroid pregnenolone sulfate (PS) and body temperature. Trpm3+/Pdgfra+ OPCs were detected in the cerebral cortex (CTX) and corpus callosum (CC) of P4 and adult rats by in situ hybridization. Trpm3 expression was detected in primary cultured rat OPCs and was increased by treatment with tumor necrosis factor α (TNFα). Application of PS (30-100 µM) increased the Ca2+ concentration in OPCs and this effect was inhibited by co-treatment with the TRP channel blocker Gd3+ (100 µM) or the TRPM3 inhibitor isosakuranetin (10 µM). Stimulation of TRPM3 with PS (50 µM) did not affect the differentiation or migration of OPCs. The number of Trpm3+ OPCs was markedly increased in demyelinated lesions in an endothelin-1 (ET-1)-induced ischemic rat model. In conclusion, TRPM3 is functionally expressed in OPCs in vivo and in vitro and is upregulated in inflammatory conditions such as ischemic insults and TNFα treatment, implying that TRPM3 is involved in the regulation of specific behaviors of OPCs in pathological conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
Enfermedades Desmielinizantes
/
Canales Catiónicos TRPM
/
Accidente Vascular Cerebral Lacunar
/
Células Precursoras de Oligodendrocitos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biol Pharm Bull
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Japón