Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties
| Autor: | Anirban Basu, Susan J. Vannucci, Jaimie L Myrkalo, Sandra J. Hewett, Ellora Sen, Tracy F. Uliasz, Steven W. Levison, Lisa B. Willing |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
IL-1
interleukin-1 Excitotoxicity HBSS Hepes-buffered salt solution MCT-1 monocarboxylate transporter-1 medicine.disease_cause GS glutamine synthetase MTT 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyl-2H-tetrazolium bromide 0302 clinical medicine P6 postnatal day 6 Hypoxia Ischemic Preconditioning Cells Cultured Neurons 0303 health sciences DMEM Dulbecco's modified Eagle's medium dbcAMP dibutyryl-cAMP LDH lactate dehydrogenase General Neuroscience Glutamate receptor glutamine synthetase EAAT-1 excitatory amino acid transporter-1 Cell Differentiation stroke Cell biology Excitatory Amino Acid Transporter 1 medicine.anatomical_structure cell death Neuroprotective Agents GAPDH glyceraldehyde-3-phosphate dehydrogenase transporter Excitatory postsynaptic potential medicine.symptom excitotoxicity Astrocyte Research Article Programmed cell death H/I hypoxia–ischaemia Glutamic Acid glutamate Biology S3 CNS central nervous system Neuroprotection S2 S5 lcsh:RC321-571 03 medical and health sciences Glutamate-Ammonia Ligase Glutamine synthetase Glial Fibrillary Acidic Protein medicine Animals Rats Wistar lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 030304 developmental biology GFAP glial fibrillary acidic protein Hypoxia (medical) Rats TBS Tris-buffered saline nervous system Animals Newborn CP ceruloplasmin Astrocytes Neurology (clinical) Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | ASN NEURO ASN Neuro, Vol 3 (2011) |
| ISSN: | 1759-0914 |
| Popis: | Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic proteinpositive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress. |
| Databáze: | OpenAIRE |
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