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INTRODUCTION: Parkinson’s disease (PD), one of the most common neurological disorder, is characterized by the loss of dopaminergic neurons in substantia nigra and striatum (ST). The typical reaction of central nervous system (CNS) on neurodegenerative processes is microglia activation and the inflammatory reaction. The data suggests that increased level of α‑synuclein (ASN), a small protein which is the major component of Lewy bodies, can induce microglia activation. Activated microglial cells release proinflammatory and potentially cytotoxic substances like cytokines. Till now, little is known about in vivo effects of exogenous ASN monomers on initiation of neuroinflammation and neurodegeneration. AIM(S): The aim of the present study was to examine the effect of increased ASN monomers concentration on microglia response and expression of pro‑ and anti‑inflammatory cytokines (interleukin 1α (IL‑1α), IL‑10, IL‑12) in the ST. METHOD(S): Male and female C57Bl/10 Tar mice 9 month-old were used in this study. Human recombinant ASN was bilaterally administered into ST (single treatment – 4 μg / structure, 8 μg per brain) and mice were decapitated after 4 or 12 weeks post injection. The changes in the level of inflammatory factors in ST were evaluated using Real-Time PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed increased level of a microglia marker – ionized calcium-binding adapter molecule 1 (IBA1) protein after ASN injection into ST. We noticed also some differences in the level of one of the most important pro inflammatory cytokines – IL‑1α. CONCLUSIONS: Our study showed that monomers of ASN are strongly involved in the inflammatory reaction in the murine CNS. Further studies are required to reveal the detailed mechanism of the influence of ASN on neuroinflammation in course of Parkinson’s disease. FINANCIAL SUPPORT: This study was supported by Grant No 1M9/PM 2/16 (Medical University of Warsaw). Research subject was implemented with CePT infrastructure financed by the European Union – The Europan Regional Development Fund within the operational programme “Innovative economy for 2007–2013.
INTRODUCTION: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. It is characterized by a progressive loss of dopaminergic neurons accompanied by a decreased concentration of dopamine (DA) and its metabolites in the striatum (ST). Experimental and clinical data indicate that α‑synuclein (ASN) plays an important role in many processes observed in the brains of patients with PD, such as disorder homeostasis of dopamine (DA) or initiate of oxidative stress. Changes in ASN levels due to its aggregation, overexpression or decreased expression may disrupt DA homeostasis and contribute to the neurodegeneration process observed in PD. AIM(S): The aim of the present study was to investigate the influence of cerebral injection of ASN on neurotransmitters level in ST. We also examine the expression of tyrosine hydroxylase gene (TH, the rate-limiting enzyme of catecholamine biosynthesis) and tissue transglutaminase 2 gene (TG2; an enzyme involved in aggregation of ASN). METHOD(S): Male and female C57Bl/10 Tar mice 9 month-old were used in this study. Human recombinant ASN was bilaterally administered into ST (4 μg/structure, 8 μg per brain) and mice were decapitated after 4 or 12 weeks post injection. Concentration of striatal neurotransmitters were measured by high performance liquid chromatography (HPLC). The gene expressions were examined by Real Time PCR. RESULTS: Intracerebral administration of ASN monomers led to changes in concentrations of striatal neurotransmitters but do not affect the expression of TH gene. The ASN administered intracerebrally into ST increases striatal expression of TG2 gene, which can lead to enhanced ASN aggregation. CONCLUSIONS: The biochemical changes observed after ASN administration may initiate further neurodegenerative processes and probably represent a very early stage in development of PD. Further research must be conducted to better understand the crucial role of ASN in the neurodegenerative process in PD. FINANCIAL SUPPORT: This study was supported by Grant No. 1M9/PM 2/16 (Medical University of Warsaw). Research subject was implemented with CePT infrastructure financed by the European Union – The Europan Regional Development Fund within the operational programme “Innovative economy for 2007–2013.
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