Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after gliotoxic lesion in the rat brainstem

Abstract

Objective: The aim of this study was to evaluate the effect of diabetic hyperglycemia on astrocyte function, estimated by means of glial fibrillary acidic protein -GFAP -immunohistochemical expression. Materials and methods: Adult male rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 microlitres 0.1% EB solution or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB or 0.9% saline solution were also injected in non-diabetic rats. Animals were anesthetized and perfused through the heart 15 and 31 days after EB or saline injection, and brainstem sections were collected for ultrastructural analysis and GFAP immunohistochemical staining. Results: The GFAP brown-stained areas were evaluated by colorimetry using a computerized image analysis system and the results have shown that diabetes hindered the increase of GFAP astrocyte expression in the EB-injected group compared to non-diabetic animals. However, diabetes did not affect GFAP response in the saline-injected group or in control animals. Conclusion: Streptozotocin-induced diabetic condition reduced astrocytic GFAP expression following gliotoxic injury. Arq Bras Endocrinol Metab. 2013;57(6):431-6 Keywords Astrocytes; GFAP; central nervous system; diabetes mellitus; ethidium bromide RESUMO Objetivo: O objetivo deste estudo foi avaliar o efeito da hiperglicemia na função astrocitária, estimada pela expressão imuno-histoquímica da proteína glial fibrilar ácida -GFAP. Materiais e métodos: Ratos machos adultos receberam uma injeção intravenosa única de estreptozotocina (50 mg/kg) e foram submetidos, 10 dias após, à injeção de 10 microlitros de solução de BE 0,1% ou de salina 0,9% na cisterna pontina. Dez microlitros de BE 0,1% ou salina 0,9% foram também injetados em ratos não diabéticos. Os animais foram anestesiados e perfundidos por via intracardíaca aos 15 e 31 dias pós-injeção de BE ou salina, e amostras de tronco encefálico foram coletadas para estudo ultraestrutural e análise imuno-histoquímica para a GFAP. Resultados: Utilizando um sistema computadorizado de análise de imagens, os resultados das áreas coradas em marrom pela GFAP, medidas por colorimetria, mostram que o diabetes reduziu o aumento de expressão dessa proteína no grupo injetado com BE em comparação aos animais não diabéticos, mas não alterou a resposta no grupo injetado com salina ou nos controles diabéticos. Conclusão: O estado diabético induzido pela estreptozotocina reduziu a expressão astrocitária de GFAP após dano gliotóxico. Arq Bras Endocrinol Metab. 2013;57(6):431-6 Descritores Astrócitos; GFAP; sistema nervoso central; diabetes melito; brometo de etídio

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

“…Diabetic rats presented lesions similar to those observed in earlier investigations (13)(14)(15)24) involving EB injection in streptozotocin-induced diabetes and comparable to those observed in cyclophosphamide immunosuppressed rats (5), in which large amounts of myelin debris and demyelinated axons were found as well as delayed remyelination by both oligodendrocytes and Schwann cells. The persistence of myelin-derived membranes in an expanded extracellular space suggested that somehow phagocytic activity was impaired (13).…”

“…The EB-induced lesions were similar to those previously described in the brainstem of diabetic (13)(14)(15) and non-diabetic rats (1)(2)(3)(4)(5)(6). In general terms, they were characterized by demyelinated areas in the ventral surface of the pons and mesencephalon, con-taining in the central region phagocytic cells, variable amounts of myelin-derived membranes in a distended extracellular space as well as naked axons.…”

“…The persistence of myelin-derived membranes in an expanded extracellular space suggested that somehow phagocytic activity was impaired (13). Diabetes has also shown to decrease GFAP expression in reactive astrocytes around EB-induced lesions (15). The mechanisms by which the diabetic state affect CNS glial cells, such as oligodendrocytes, and astrocytes, remain unclear.…”

“…On the other hand, insulin treatment prevented diabetes-induced alterations in astrocyte glutamate uptake and reverted the decreased GFAP expression in rats at 4 and 8 weeks of diabetes duration (12). Glial modifications were clearly pointed in some studies using streptozotocin-diabetic rats after the injection of EB (13)(14)(15), with marked delay on macrophagic scavenging activity of myelin debris, on oligodendrocyte and Schwann cell remyelination (13), on blood-brain barrier repair (14) as well as on glial fibrillary acidic protein (GFAP) expression in reactive astrocytes at the periphery of the injury site (15).…”

Rauwolfia vomitoria and Gongronema latifolium extracts influences cerebellar cortex

“…How-ever, it is reported that apparent decreased GFAP content reflects a decrease in GFAP expression, but may not be a decrease in the number of astrocytes [62].…”