title: The effect of α-synuclein on gliosis and IL-1α, TNFα, IFNγ, TGFβ expression in murine brain.
abstract: BACKGROUND
  Alpha - synuclein (ASN) is the principal component of Lewy pathology and strongly influences on the pathogenesis of Parkinson's disease (PD). The increased level of ASN protein causes microglial response. The reactive microglial cells may actively participate in the damaging of dopaminergic neurons. The data suggests that ASN accumulation in astrocytes might damage these cells in the substantia nigra pars compacta (SN) and promotes degeneration of dopaminergic neurons in SN. We examined the potential role of recombinant ASN monomers as a major pathogenic factor causing the inflammatory response in the central nervous system.
  
  
  METHODS
  Mice were bilaterally infused by human ASN monomers into the striatum (ST) or SN (single treatment was 4μg/structure, 8μg per brain) and decapitated after 1, 4 or 12 weeks post injection. The changes in the level of inflammatory factors in ST were evaluated using Real-Time PCR and Western Blot method. The analysis of morphological changes of glial cells was performed by immunohistochemical staining.
  
  
  RESULTS
  We observed a strong activation of microglia cells in ST and increased expression of striatal interleukin 1α, tumor necrosis factor alpha and interferon gamma after ASN injection into the ST. We noticed an increase in striatal glial fibrillary acidic protein mRNA level 4 weeks after ASN injection into the ST. Injection of ASN into the SN led to an increase of striatal transforming growth factor beta mRNA level and has no influence on striatal glial fibrillary acidic protein mRNA level.
  
  
  CONCLUSIONS
  Our results suggest that both the microglia activation and supressing astrocytes play a crucial role in ASN-related dopaminergic neurotoxicity.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warszawa, Centre for Preclinical Research and Technology CePT, Warszawa, Poland. Electronic address: anna.sznejder@wum.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Sznejder-Pachołek
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warszawa, Centre for Preclinical Research and Technology CePT, Warszawa, Poland. Electronic address: ilona.joniec@wum.edu.pl.
authors.forename: Ilona
authors.initials: I
authors.lastname: Joniec-Maciejak
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warszawa, Centre for Preclinical Research and Technology CePT, Warszawa, Poland. Electronic address: adriana.wawer@wum.edu.pl.
authors.forename: Adriana
authors.initials: A
authors.lastname: Wawer
authors.affiliation: Department of Neurosurgery, University of California at San Francisco, San Francisco, CA, USA. Electronic address: agnieszka.ciesielska@ucsf.edu.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ciesielska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University of Warszawa, Centre for Preclinical Research and Technology CePT, Warszawa, Poland; 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warszawa, Poland. Electronic address: dmirowska@wum.edu.pl.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Mirowska-Guzel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D010300:Parkinson Disease; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D053582:Interleukin-1alpha; C497604:SNCA protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein; D007371:Interferon-gamma; D004298:Dopamine
keywords: Alpha-synuclein; Cytokines; Gliosis; Neuroinflammation; Parkinson’s disease