Astrogliosis in a dish: substrate stiffness induces astrogliosis in primary rat astrocytes
| Autor: | Stephen L. Hayward, Srivatsan Kidambi, Christina L. Wilson |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal structures General Chemical Engineering macromolecular substances Article 03 medical and health sciences medicine chemistry.chemical_classification Reactive oxygen species Glial fibrillary acidic protein biology Super oxide dismutase Chemistry technology industry and agriculture General Chemistry equipment and supplies medicine.disease Phenotype In vitro Astrogliosis Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein Signal transduction Astrocyte |
| Zdroj: | RSC Adv |
| ISSN: | 2046-2069 |
| DOI: | 10.1039/c5ra25916a |
| Popis: | Astrogliosis due to brain injury or disease can lead to varying molecular and morphological changes in astrocytes. Magnetic resonance elastography and ultrasound have demonstrated that brain stiffness varies with age and disease state. However, there is a lack in understanding the role of varied stiffness on the progression of astrogliosis highlighting a critical need to engineer in vitro models that mimic disease stages. Such models need to incorporate the dynamic changes in the brain microenvironment including the stiffness changes. In this study we developed a polydimethyl siloxane (PDMS) based platform that modeled the physiologically relevant stiffness of brain in both a healthy (200 Pa) and diseased (8000 Pa) state to investigate the effect of stiffness on astrocyte function. We observed that astrocytes grown on soft substrates displayed a consistently more quiescent phenotype while those on stiff substrates displayed an astrogliosis-like morphology. In addition to morphological changes, astrocytes cultured on stiff substrates demonstrated significant increase in other astrogliosis hallmarks – cellular proliferation and glial fibrillary acidic protein (GFAP) protein expression. Furthermore, culturing astrocytes on a stiff surface resulted in increased reactive oxygen species (ROS) production, increased super oxide dismutase activity and decreased glutamate uptake. Our platform lends itself for study of potential therapeutic strategies for brain injury focusing on the intricate brain microenvironment-astrocytes signaling pathways. |
| Databáze: | OpenAIRE |
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