Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.
ASN Neuro
; 2(2): e00030, 2010 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-20396375
Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15-25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20-24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.
Palavras-chave
4-PBA, 4-phenylbutyric acid; 6-NBDG, 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose; Cx, connexin; DCF, 2',7'-dichlorodihydrofluorescein; DIC, differential interference contrast; DMEM, Dulbecco's modified Eagle's medium; ER, endoplasmic reticulum; FBS, fetal bovine serum; LYCH, Lucifer Yellow CH; LYVS, Lucifer Yellow VS; MnTBAP, manganese(III) tetrakis (4-benzoic acid) porphyrin chloride; NA, numerical aperture; NOS, nitric oxide synthase; PKC, protein kinase C; RNS, reactive nitrogen species; ROS, reactive oxygen species; STZ, streptozotocin; TMAO, trimethylamine N-oxide dihydrate; TUDCA, tauroursodeoxycholic acid; aCSF, artificial cerebrospinal fluid; astrocyte; carboxy-DCF-DA, carboxy DCF diacetate; connexin (Cx); dBcAMP, dibutyryl cAMP; diabetes; gap junction; hyperglycaemia; l-NAME, l-Nω-nitro-l-arginine methyl ester; streptozotocin
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Comunicação Celular
/
Astrócitos
/
Junções Comunicantes
/
Diabetes Mellitus Experimental
/
Hiperglicemia
Limite:
Animals
Idioma:
En
Revista:
ASN Neuro
Assunto da revista:
NEUROLOGIA
/
QUIMICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos