Abstract
Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+ release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+ release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+ overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+ release and ER stress.
Highlights
Astrocytes are ubiquitous in central nervous system (CNS) and mediate multiple functions via releasing nutrients, growth factors, cytokines, and several neurotransmitters, thereby interacting with neurons and other glial cells [1]
Primary cultured spinal cord astrocytes were isolated from newborn rats
As glial fibrillary acidic protein (GFAP) is specially expressed in the astrocytes, before experiment, GFAP antibody was used to identify the purity of astrocytes
Summary
Astrocytes are ubiquitous in central nervous system (CNS) and mediate multiple functions via releasing nutrients, growth factors, cytokines, and several neurotransmitters, thereby interacting with neurons and other glial cells [1]. External stimuli could induce sustained release of some neurotransmitters in neuronal and glial cells. Glutamate, an important excitatory neurotransmitter, could activate calcium signals and mediates interaction between neuronal and glial cells [4]. During early stage of glutamate elevation, glutamate receptor in astrocytes could be activated preferentially to minimize the deleterious effect of glutamate on neuronal cells [6,7]. Prolonged activation by glutamate induces apoptosis in astrocytes, subsequently causing CNS injury [7]. Astrocytes act as a defender in glutamate-induced neuronal cell apoptosis. Excitotoxicity and oxidative stress have been reported to participate in glutamate-induced cytotoxicity [8,9], but the precise underlying mechanism still needs further investigation
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