The role of cyclin-dependent kinase 5 in regulating early inflammatory signaling in the mouse brain during amyloid beta toxicity

• Autorzy: Czapski G.A. , Wilkaniec A. , Gassowska-Dobrowolska M. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Cyclin-dependent kinase 5 (Cdk5) belongs to the family of serine/threonine kinases and plays a fundamental role in brain development and functioning, but its deregulated activity has also been implicated in various neurodegenerative disorders, including Alzheimer’s disease (AD). Moreover, our recent study demonstrated the involvement of Cdk5 in regulating inflammatory processes in the brain during peripheral activation of immune system. However, the relationship between AD, Cdk5 and neuroinflammation is poorly understood. AIM(S): The aim of this study was to investigate the involvement of Cdk5 in regulating neuroinflammation in mouse model of amyloid beta (Aβ) toxicity METHOD(S): Here, we used the experimental model, based on single intracerebroventricular injection of Aβ1‑42 oligomers, enabling the production of Alzheimer-like behavioral abnormalities and resembling some molecular events occurring during early stage of AD. The brain tissue was analyzed up to 35 days post-injection. The role of Cdk5 in inflammatory process activation was evaluated using the pharmacological Cdk5 inhibitor roscovitine. RESULTS: Our results demonstrated that injection of Aβ1‑42 oligomers induces long‑lasting activation of microglia and astrocytes in hippocampus. Analysis of mRNA level for inflammation‑related genes (e.g. Tnf‑α, IL‑1β, IL‑6) showed rapid rise as early as 3 h after injection of Aβ1‑42. Notably, injection of scrambled Aβ1‑42 had no effect on expression of inflammatory mediators. Furthermore, Aβ1‑42 promotes p25 generation, indicative of increased Cdk5 activity. Importantly, inhibition of Cdk5 with roscovitine significantly reduced gene expression and/or protein level of Tnf‑α, IL‑1β, IL‑6, IL‑10 and Nos2. CONCLUSIONS: Our data indicated that Cdk5 plays an important role in Aβ toxicity via controlling brain inflammatory processes. These findings provide important new insights into the molecular mechanisms linking neuroinflammation with the pathogenesis of Alzheimer’s disease. FINANCIAL SUPPORT: This study was supported by The NCN Grant 2011/03/B/NZ3/04549.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.59

Twórcy

autor

Czapski G.A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Wilkaniec A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Gassowska-Dobrowolska M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland