The influence of alpha-synuclein on neurodegenerative processes in the murine brain

• Autorzy: Wojnar E. , Wawer A. , Joniec-Maciejak I. , Sznejder-Pachołek A. , Mirowska-Guzel D.
• Języki publikacji: EN

Abstrakty

EN

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.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.73-74

Twórcy

autor

Wojnar E.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Wawer A.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Joniec-Maciejak I.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Sznejder-Pachołek A.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Mirowska-Guzel D.

• Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
• Institute of Psychiatry and Neurology, Warsaw, Poland