Cerebral administration of alpha synuclein modulates inflammatory reaction in the nigro striatal system: A comparison of males and females

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

Abstrakty

EN

INTRODUCTION: The risk of developing Parkinson’s disease (PD) is twice as high among men as among women. Estrogens appear to be a protective factor. The progression of PD is characterized by inflammation, especially the activation of the microglia. The data suggests that increased levels of α‑synuclein (ASN) can induce microglia activation. Activated microglial cells release pro‑ and anti‑inflammatory cytokines. AIM(S): The aim of this study was to investigate the role of increased ASN monomers concentration as a major pathogenic factor causing microglia response and changes in the expression of mRNA of inflammatory cytokines (i.e., interleukin 1α (IL‑ α), IL‑10, IL‑12 and tumor necrosis factor α (TNFα)) in the striatum (ST). We also examined the levels of ionized calcium binding adaptor molecule 1 (Iba‑1). We evaluated the differences between the genders after injection of ASN. METHOD(S): Male and female C57Bl/10 Tar 9-month- ‑old mice 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. Changes in the level of inflammatory factors in ST were evaluated using Real‑Time PCR. RESULTS: We observed increased levels of a microglia marker, Iba1 protein, in all experimental groups after 4 weeks of injection of ASN into the ST, with the highest differences in the FOVA group (female after ovariectomy). IL‑10 mRNA levels were significantly elevated in the FOVA group at 4 weeks after ASN administration intothe ST as compared to the ovariectomy control group. We noticed differences in levels of IL‑1α, IL‑12, and TNFα mRNA between the genders after injection of ASN. CONCLUSIONS: Our results support the hypothesis of pro‑inflammatory actions of ASN monomers. Injection of ASN into the ST induces microglia activation. Estrogens appear to be an important factor in the inflammatory reaction in the murine model of Parkinson’s disease after cerebral administration of ASN.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXXVIII

Twórcy

autor

Sznejder-Pacholek A.

• Centre for Preclinical Research and Technology (CePT), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Joniec-Maciejak I.

• Centre for Preclinical Research and Technology (CePT), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Wawer A.

• Centre for Preclinical Research and Technology (CePT), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Wojnar E.

• Centre for Preclinical Research and Technology (CePT), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Mirowska-Guzel D.

• Centre for Preclinical Research and Technology (CePT), Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
• Institute of Psychiatry and Neurology, Warsaw, Poland