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 -