title: Screening of Toll-like receptors expression in multiple system atrophy brains.
abstract: The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. It was recently suggested that TLRs have an important role in the crosstalk between neurons and glial cells in the central nervous system, thus their deregulation may play a role in neurodegeneration. Multiple system atrophy (MSA) together with Parkinson's disease belongs to a diverse group of neurodegenerative conditions termed α-synucleinopathies. MSA is a fatal late onset disease characterized by the presence of α-synuclein positive glial cytoplasmic inclusions in oligodendrocytes. α-Synuclein can act as a danger-associated molecular pattern and alter TLR expression thereby activating inflammatory responses in the brain. In this study, using real-time PCR, we assessed the expression of TLRs (TLR1-10) in selected areas of MSA brains (substantia nigra, striatum, cerebral cortex, and nucleus dentatus) in comparison with normal controls. We show evidence for increased levels of mRNA-encoding hTLR-3, hTLR-4, and hTLR-5 in substantia nigra, striatum, cerebral cortex, and nucleus dentatus from MSA brains versus normal controls. The levels of expression of hTLR-1 mRNA were elevated in substantia nigra and striatum whereas levels of hTLR-8 and hTLR-9 mRNAs were significantly higher in cerebella from MSA patients. The concerted alteration of expression of multiple TLRs in MSA brains can be of relevance for understanding the pathogenesis of the disease.
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark. tomasz.brudek@regionh.dk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brudek
authors.forename: Kristian
authors.initials: K
authors.lastname: Winge
authors.forename: Tina Klitmøller
authors.initials: TK
authors.lastname: Agander
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002525:Cerebellar Cortex / Q000378:metabolism; D002529:Cerebellar Nuclei / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000473:pathology / Q000503:physiopathology*; D009457:Neuroglia / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism; D051193:Toll-Like Receptors / Q000096:biosynthesis*
chemical_list: D051193:Toll-Like Receptors