Influence of systemic inflammation and fluctuations of blood glucose level on amyloidopathy progression in mouse model of sporadic Alzheimer’s disease

• Autorzy: Wieckowska A. , Wydrych M. , Mietelska-Porowska A. , Wojda U.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Prominent neuropathologic features of Alzheimer’s Disease (AD) are the appearance of senile plaques composed of amyloid peptides and neurofibrillary tangles derived from Tau protein. Induction of main risk factors before the appearance of typical neuropathological AD hallmarks can help to track the sequence of different and complicated early molecular mechanisms of the sporadic form of human AD (SAD). AIM(S): Our aim is to establish a mouse model that would mimic molecular mechanisms leading to SAD by induction of systemic neuroinflammation and insulin resistance in transgenic mice with mutated human gene encoding amyloid precursor protein (Tg APP). Additionally, we would like to check whether the same experimental conditions may induce AD hallmarks in wild type mice, that may be a proof of lifestyle factors influence on AD development. METHOD(S): In order to induce neuroinflammation and evaluate the influence of insulin dysregulation in the brain, Tg APP and C57BL mice were injected with LPS, and diabetes was induced by high-fat diet feeding, or streptozocin injection. Every two weeks blood glucose level and body weight were checked. To characterize the metabolic phenotype and immunostaining pattern of neuroinflammatory markers and amyloid β, mice blood and brain tissue were used. RESULTS: We show effects of systemic administration of infectious agent in neuroinflammation in the brain and body weight and blood biochemical pattern related to high-fat diet and their relation with amyloidopathy progression in the brain. CONCLUSIONS: The data verify if lifestyle conditions including ongoing systemic inflammation and metabolic changes related to unhealthy diet may accelerate amyloidopathy progression. Studied factors may cause changes not only in Tg APP mice but also lead to the development of AD hallmarks in brain of mice without mutations in APP gene. Results might provide the evidence that the proposed animal model may be an effective tool to study the molecular mechanisms of early stages of SAD progression. FINANCIAL SUPPORT: Polish National Science Centre Grant 2014/15/D/NZ4/04361.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.63

Twórcy

autor

Wieckowska A.

• Neurobiology Center, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Wydrych M.

• Neurobiology Center, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Mietelska-Porowska A.

• Neurobiology Center, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Wojda U.

• Neurobiology Center, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland