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Altered Brain Hemoglobin Gene Expression in the Frontal Cortex of Patients with Alzheimer's and Acquired Creutzfeldt‐Jakob's Disease
Author(s) -
Vanni Silvia,
Zattoni Marco,
Moda Fabio,
Tagliavini Fabrizio,
Haik Stephane,
Deslys JeanPhilippe,
Zanusso Gianluigi,
Ironside James W,
Ferrer Isidre,
Kovacs Gabor,
Legname Giuseppe
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb136
Subject(s) - disease , gene , pathology , pathological , biology , hemoglobin , temporal cortex , medicine , virology , neuroscience , genetics
Objective The aim of this study was to shed light on the molecular mechanism involved in the onset and the progression of human prion diseases. In particular, we investigated specific alterations that occur in variant and iatrogenic forms of Creutzfeldt‐Jakob disease (vCJD and iCJD) infected brains in comparison to other sporadic (sCJD) or genetic (gCJD) prion and non‐prion neurodegenerative diseases. Methods We collected 132 samples from frontal cortex of frozen brain tissue, from prion‐infected patients (vCJD n=20, iCJD n=11, sCJD n=25, gCJD = 28), patients with Alzheimer's disease (AD n=18) and age‐matched controls (n=30). RNA was extracted and only samples with a RIN≥5 were included in the study RT‐qPCR was performed for the selected transcripts, with ACTB , RPL19, GAPDH and B2M as reference genes. In addition, specific erythrocyte marker ( ALAS2 ) expression analysis was performed in order to account for the blood contamination. Results Previously (Barbisin et al . 2014), we reported a significant down‐regulation in the gene expression of both neuronal/glial hemoglobin chains (n HBB and n HBA2 ) in a macaque model of intracranial BSE‐infection. By contrast, we observed a significant up‐regulation of n HBA1/2 in vCJD brains together with a significant down‐regulation of n HBB in iCJD patients. In addition, both chains display a strong down‐regulation in AD brains, in accordance with earlier results reported in literature (Ferrer et al. 2011). Conclusions Besides an involvement of oxygen‐ and iron‐related pathways unbalance as pathological events shared among different neurodegenerative diseases, these data point towards distinct transcriptional responses depending on the neuropathological alterations in human prion diseases. In particular, the initial site of misfolding event (CNS vs peripheral tissue) and the related difference in disease timing, together with specific molecular and conformational features of the pathological agent of the disease (such as Bovine Spongiform Encephalopathy (BSE)‐derived vCJD, various sCJD and iCJD strains or other misfolded protein events such Aβ accumulation in AD) seem to determine the peculiar hemoglobin dysregulation in different neurodegenerative diseases. In conclusion, these results suggest that gene expression of n HBB and n HBA2 in the CNS is differentially affected by different prion strains. Support or Funding Information This work was supported by a Fondo per gli Investimenti della Ricerca di Base (FIRB) program project [grant number RBAP11FRE9 to G.L.] from Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) Italy.