Parkinsonian features in aging GFAP.HMOX1 transgenic mice overexpressing human HO-1 in the astroglial compartment
| Autor: | Carmela Galindez, Marisa Cressatti, Adrienne Liberman, Wei Song, Hillel Zukor, Hyman M. Schipper |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging medicine.medical_specialty Dopamine Central nervous system Gene Expression Mice Transgenic Biology Neuroprotection 03 medical and health sciences 0302 clinical medicine Internal medicine Mitophagy Glial Fibrillary Acidic Protein medicine Autophagy Animals Humans Reelin Cells Cultured Tyrosine hydroxylase Glial fibrillary acidic protein General Neuroscience Membrane Proteins Parkinson Disease Mitochondria Oxidative Stress Reelin Protein 030104 developmental biology Endocrinology medicine.anatomical_structure nervous system Astrocytes biology.protein alpha-Synuclein GABAergic Neurology (clinical) Geriatrics and Gerontology 030217 neurology & neurosurgery Heme Oxygenase-1 Developmental Biology Astrocyte |
| Zdroj: | Neurobiology of aging. 58 |
| ISSN: | 1558-1497 |
| Popis: | Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin). The neurophenotype of these GFAP.HMOX18.5-19m mice is highly consistent with parkinsonism and differs dramatically from the schizophrenia-like features previously documented in younger GFAP.HMOX10-12m mice. Common stressors may elicit either early-onset developmental (schizophrenia) or later-life degenerative (PD) brain disorders depending on whether the glial HO-1 response is engaged prior to or following the maturation of dopaminergic circuitry. Curtailment of glial HO-1 transduction at strategic points of the life course may confer neuroprotection in human degenerative and developmental central nervous system disorders. |
| Databáze: | OpenAIRE |
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