caa a22 4500 445364726 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10048-011-0294-5 doi (NATIONALLICENCE)springer-10.1007/s10048-011-0294-5 Up-regulation of metallothionein gene expression in Parkinsonian astrocytes [Elektronische Daten] [Gregory Michael, Sharmin Esmailzadeh, Linda Moran, Lynne Christian, Ronald Pearce, Manuel Graeber] The role of glial cells in Parkinson's disease (PD) is unclear. We have previously reported a striking up-regulation of DnaJB6 heat shock protein in PD substantia nigra astrocytes. Whole genome transcriptome analysis also indicated increased expression of metallothionein genes in substantia nigra and cortex of sporadic PD cases. Metallothioneins are metal-binding proteins in the CNS that are released by astrocytes and associated with neuroprotection. Metallothionein expression was investigated in 18 PD cases and 15 non-PD controls using quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridisation (ISH) and immunocytochemistry (ICC). We observed a strong increase in the expression of metallothioneins MT1E, MT1F, MT1G, MT1H, MT1M, MT1X and MT2A in both PD nigra and frontal cortex. Expression of LRP2 (megalin), the neuronal metallothionein receptor was also significantly increased. qRT-PCR confirmed metallothionein up-regulation. Astrocytes were found to be the main source of metallothioneins 1 and 2 based on ISH results, and this finding was confirmed by ICC. Our findings demonstrate metallothionein expression by reactive astrocytes in PD nigra and support a neuroprotective role for these cells. The traditional view that nigral astrocytes are non-reactive in PD is clearly incorrect. However, it is possible that astrocytes are themselves affected by the disease process which may explain their comparatively modest and previously overlooked response. Springer-Verlag, 2011 Cell death nationallicence Glial degeneration nationallicence Megalin nationallicence Neuroprotection nationallicence Reactive astrocytes nationallicence Michael Gregory Centre for Neuroscience and Trauma, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, E1 2AT, London, UK aut Esmailzadeh Sharmin The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut Moran Linda The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut Christian Lynne The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut Pearce Ronald The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut Graeber Manuel The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut neurogenetics Springer-Verlag 12/4(2011-11-01), 295-305 1364-6745 12:4<295 2011 12 10048 https://doi.org/10.1007/s10048-011-0294-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0294-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Michael Gregory Centre for Neuroscience and Trauma, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, E1 2AT, London, UK aut NATIONALLICENCE 700 1- Esmailzadeh Sharmin The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut NATIONALLICENCE 700 1- Moran Linda The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut NATIONALLICENCE 700 1- Christian Lynne The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut NATIONALLICENCE 700 1- Pearce Ronald The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut NATIONALLICENCE 700 1- Graeber Manuel The former University Department of Neuropathology, Imperial College, University of London and Hammersmith Hospitals Trust, W6 8RF, London, UK aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/4(2011-11-01), 295-305 1364-6745 12:4<295 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer