RESEARCH PAPER
Cerebral administration of alpha-synuclein monomers modulates inflammatory reaction in nigro-striatal system
 
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1
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Poland
 
2
Gladstone Institutes of Neurological Disease, United States
 
3
Department of Neurology, Institute of Psychiatry and Neurology, Poland
 
 
Corresponding author
Ilona Joniec-Maciejak   

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Banacha 1B, 02-097, Warsaw, Poland
 
 
J Pre Clin Clin Res. 2019;13(1):26-36
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
It has been established that changes in the levels of a-synuclein (ASN) are associated with Parkinson’s disease (PD). The progression of PD is characterized by immune response and inflammation, especially the activation of the microglia. Activated microglia cells release potentially cytotoxic substances, such as pro-inflammatory cytokines, caspases as well as neuroprotective molecules such as neurotrophins.

Objective:
We examined the potential role of recombinant ASN monomers as a major pathogenic factor causing inflammatory responses in the central nervous system.

Methods:
Mice were bilaterally infused with human ASN monomers into the striatum (ST) or substantia nigra pars compacta (SNpc) (single treatment was 4μg/structure, 8μg per brain) and decapitated after 1, 4 or 12 weeks post injection. The changes in the level of neurotrophins, receptor for neurotrophins, marker of microglia and adhesion molecules in ST were evaluated using Real-Time PCR. The analysis of morphological changes of T lymphocytes was performed by immunohistochemical staining.

Results:
In our study, we reported a CD4+ T-cell infiltration to the CNS following ASN delivery to ST or SNpc. We observed a slight effect of ASN on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). The present study demonstrated an increase in the expression of the glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and receptors of nerve growth factor (NGF) – TrkA, receptor of BDNF – TrkB, receptor of NT-3 – TrkC, following the administration of ASN into ST.

Conclusion:
Our research provides further evidence for the involvement of ASN in the inflammatory response in the CNS.

 
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