The impact of prenatal stress and stress in adulthood on the brain epigenome: association with the occurrence of dementia in the course of Alzheimer's disease and type 2 diabetes
Project title
The impact of prenatal stress and stress in adulthood on the brain epigenome: association with the occurrence of dementia in the course of Alzheimer's disease and type 2 diabetes
Name of Beneficiary/Beneficiaries
Institute of Pharmacology named after Jerzy Maj of the Polish Academy of Sciences
Name of programme
International programs
Competition
EU Joint Programme – Neurodegenerative Disease Research (JPND)
Project value
PLN 744,209.00
Funding value
PLN 744,209.00
Project delivery period
from January 14, 2019 to January 13, 2023
Get to know our team
Project manager: Prof. DSc. Agnieszka Basta Kaim
What problem does our project solve?
Life expectancy has been increasing in recent years, which implies a significant increase in the number of elderly people. Therefore, there is a need to know and understand the biological basis of changes leading to reduced mental performance, which accompanies both normal and pathological aging processes. Research in recent years indicates a diverse picture of the appearance and course of behavioral and cognitive dysfunctions occurring in older people, both in terms of their course and the intensity of symptoms. For example, the picture of dementia observed in patients with Alzheimer's disease (AD) differs from the picture of dementia accompanying normal aging, in the course of which, apart from changes typical of old age, there are usually no severe neurodegenerative changes, including the formation of β-amyloid deposits typical of AD. Therefore, the question arises whether there are factors, including environmental ones, that determine the occurrence of dementias with various histopathological patterns, and at the same time factors that can modulate their molecular/biochemical basis?
In our project, we undertook to verify and assess whether stress, especially prenatal stress, affects the development of the offspring's central nervous system and whether its long-term effects may have a role in the course of age-related cognitive deficits in both physiological and pathological aging.
Who will benefit from the project results?
The results of the research presented in the project indicated a comprehensive basis for cognitive deficits observed in the course of dementia induced by both old age, metabolic disorders and AD pathology. Their analysis can be used as a basis for new points of reference for the pharmacotherapy of these processes, especially considering the limited effectiveness of currently used methods of treating them.
What was the biggest challenge for us in implementing the project?
The research was carried out in animal models using the latest tools, including transgenic mice obtained using the "knock-in" technique of fragments of the promoter of the human amyloid gene, which, on the one hand, made it possible to conduct long-term observations and biochemical, behavioral and cognitive analyzes comparatively in ontogeny in physiological processes, but also pathological aging up to the 20th month of life of animals, and on the other hand it was extremely time-consuming, complicated and cost-intensive. Therefore, we believe that the results obtained will have a high translational value and will constitute the basis for obtaining further projects allowing their continuation.