Regional differences in neuroinflammation-associated gene expression in the brain of sporadic creutzfeldt–jakob disease patients
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Regional differences in neuroinflammation-associated gene expression in the brain of sporadic creutzfeldt–jakob disease patients. / Areškevičiūtė, Aušrinė; Litman, Thomas; Broholm, Helle; Melchior, Linea C.; Nielsen, Pia R.; Green, Alison; Eriksen, Jens O.; Smith, Colin; Lund, Eva L.
I: International Journal of Molecular Sciences, Bind 22, Nr. 1, 140, 2021, s. 1-17.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Regional differences in neuroinflammation-associated gene expression in the brain of sporadic creutzfeldt–jakob disease patients
AU - Areškevičiūtė, Aušrinė
AU - Litman, Thomas
AU - Broholm, Helle
AU - Melchior, Linea C.
AU - Nielsen, Pia R.
AU - Green, Alison
AU - Eriksen, Jens O.
AU - Smith, Colin
AU - Lund, Eva L.
PY - 2021
Y1 - 2021
N2 - Neuroinflammation is an essential part of neurodegeneration. Yet, the current under-standing of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroin-flammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt–Jakob disease. The analysis was performed using NanoString nCounter technology with human neuroinflammation panel+. The observed gene expression patterns were regionally and sub-regionally distinct, suggest-ing a variable neuroinflammatory response. Interestingly, the observed differences could not be explained by the molecular subtypes of sporadic Creutzfeldt–Jakob disease. Furthermore, analyses of canonical pathways and upstream regulators based on differentially expressed genes indicated an overlap between biological processes taking place in different brain regions. This suggests that even smaller-scale spatial data reflecting subtle changes in brain cells’ functional heterogeneity and their immediate pathologic microenvironments are needed to explain the observed differential gene expression in a greater detail.
AB - Neuroinflammation is an essential part of neurodegeneration. Yet, the current under-standing of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroin-flammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt–Jakob disease. The analysis was performed using NanoString nCounter technology with human neuroinflammation panel+. The observed gene expression patterns were regionally and sub-regionally distinct, suggest-ing a variable neuroinflammatory response. Interestingly, the observed differences could not be explained by the molecular subtypes of sporadic Creutzfeldt–Jakob disease. Furthermore, analyses of canonical pathways and upstream regulators based on differentially expressed genes indicated an overlap between biological processes taking place in different brain regions. This suggests that even smaller-scale spatial data reflecting subtle changes in brain cells’ functional heterogeneity and their immediate pathologic microenvironments are needed to explain the observed differential gene expression in a greater detail.
KW - Biomarkers
KW - Brain microenvironment
KW - Creutzfeldt–Jakob disease
KW - Gene expression analysis
KW - Immune re-sponse
KW - Microglia
KW - Neuroinflammation
KW - Prion disease
KW - Regional pathogenesis
U2 - 10.3390/ijms22010140
DO - 10.3390/ijms22010140
M3 - Journal article
C2 - 33375642
AN - SCOPUS:85098771074
VL - 22
SP - 1
EP - 17
JO - International Journal of Molecular Sciences (CD-ROM)
JF - International Journal of Molecular Sciences (CD-ROM)
SN - 1424-6783
IS - 1
M1 - 140
ER -
ID: 254989949