Neurobiology of disease

Research group

The main goal of our research is to understand the mechanisms that lead to neurodegenerative diseases and to identify novel therapeutic approaches for them. We are interested in the effects of environmental agents (such as air pollution and viral infections) and lifestyle factors on brain health and in Alzheimer's disease. We also study the impact of the environment on mental health in children and adolescents.

We are currently studying transcellular and intercellular communication in neurodegenerative diseases, oxidative stress in astrocytes during neurodegeneration, the importance of Nrf2 in mitochondria, mitochondrial degradation: mechanisms and consequences in neurodegenerative diseases, biometal homeostasis in neurodegenerative diseases, and neurogenesis alterations in disease. We utilize several in vitro and in vivo models of neurodegenerative disease, including human brain cells. We employ a range of behavioral tests and magnetic resonance imaging to measure the outcome of therapeutic interventions in mouse models. We also utilize confocal imaging, ex vivo slice cultures and sophisticated gene transfer technologies in our research. We have recently developed a new model of the human olfactory mucosa.

Funder(s)

Other funders

European Commission

Neurobiology of disease funder logo

Academy of Finland

Neurobiology of disease funder logo

Sigrid Juselius foundation

Neurobiology of disease funder logo

JPco-fuND

Neurobiology of disease funder logo

Finnish Cultural foundation

Neurobiology of disease funder logo

Organization

A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences

Keywords

    • TUBE, Transport derived Ultrafines and the Brain Effects​

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      European Commission Horizon 2020 funded project with multidiciplinary collaboration around Europe and beyond

      • Air pollution is known to cause manifold harmful effects to our health. Beyond lungs and cardiovascular system, the brain is also targeted by this ambient threat. Despite the mounting evidence of the connection of air pollution to neurological disorders, and especially to Alzheimer’s disease, we are still lacking knowledge of the spesific cellular and molecular mechanims of how air pollution affects brain health
      • The TUBE project aims to decipher effects of traffic related ultrafine (UFP) air pollutants  to brain health and understanding the adverse effects of air pollution on the cellular and molecular level.
      • Combines interdisciplinary expertise to model effects of UFPs in the human brain
      • Provides new information to support political decicion making about emission regulations 
      • More information: https://www.tube-project.eu/

    • ADAIR, Alzheimer’s Disease and Air Pollution​

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      JPND funded project with multi-national collaboration between neuroscientists, environmental scientists, clinicians, epidemiologists, informaticians, and non-profit organisations

      • ADAIR applies a precision medicine approach to stratify individuals to subgroups for risk estimation and future Alzheimer’s disease (AD) prevention, ultimately aiming to target air pollution induced effects in those individuals that can most benefit from them
      • The project investigates the novel, ambitious hypothesis that the pollutant exposure environment of an individual alters cellular mechanisms and functions, resulting in the expression of measurable biomarkers. By identifying biomarkers, the individuals with increased AD risk can be stratified prior to the disease onset and preventive measures can be targeted to the specific at-risk populations in order to be most effective.
      • We use a unique recently developed exposure system that combines the air–liquid interface and exposure to complete emissions. This exposure system represents the realistic setting that mimics real-world traffic pollutant exposure. 
      • More information: https://adair-jpnd.eu/

    • Equal-Life

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      European Commission Horizon 2020 funded project with multidiciplinary expertise of 20 partners from 11 European countries. 

      • Mental health is the result of the complex interplay between genetic, psychological, environmental and other factors and experiences.
      • The exposome concept, referring to the totality of exposures from conception onwards, is emerging as a very promising approach in studying the role of the environment in human disease.
      • The Equal-Life project will develop and utilise the exposome concept in an integrated study of the external exposome and its social aspects and of measurable internal physiological factors and link those to a child’s development and life course mental health. 
      • Our aim is to discover novel internal biomarkers in relation to children’s mental health. The specific focus lies in the discovery of proteomic, metabolomic and DNA-based biomarkers in bodily fluids. 
      • More information: https://equal-life.eu/en/project

    • COVID-19 viral impact at the human olfactory mucosa​

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      • The Academy of Finland funded project to provide insight into viral impacts in the cells of the human nasal cavity.
      • Since the start of the COVID-19 pandemic, neurological manifestations associated with COVID-19 have been reported in many patients
      • Exact mechanisms of COVID-19 neurological manifestations remain unknown
      • The Naso-olfactory route is one of hypothesised pathways for the virus to enter the brain. During this project we have developed a novel 3D cell model to mimic the Nose-Brain axis.
      •  We aim to
      • Elucidate mechanisms of  SARS-CoV2 entery in the human olfactory mucosa.
      • Decipher neuroinvasive potential of SARS-CoV2 virus through the olfactory route
      • Investigate the role of pre-exsisting or genetic predesposition to Alzheimer’s disease in SARS-CoV2 associated neurotropism.
      • Our goal is to highlight the vulnerabilities associated with COVID-19 andto provide scientific insight for preventive and therapeutic interventions.

    • The role of olfactory mucosa cells in Alzheimer's disease​

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      • A project funded by the Sigrid Juselius foundation and the Academy of Finland
      • Olfactory dysfunction is observed early in several neurodegenerative disorders. The sense of smell is orchestrated by olfactory mucosal cells located at the roof top of the nasal cavity. However, it is unclear how these cells reflect key features in Alzheimer’s disease (AD) in vitro
      • We utilize the cultured olfactory mucosa (OM) cells derived from living individuals to model late-onset Alzheimer’s disease in vitro. The OM cells are relatively cost-efficient and straightforward to maintain in culture compared to the other existing cell models of AD. The cells do not require reprogramming and provide a source for neural tissue of living individuals. 
      • The model has various applications from drug screening purposes to finding solutions for the early detection of AD.

       

      For more information, please see the following research articles: 

      Lampinen R*, Fazaludeen MF*, Avesani S, Örd T, Penttilä E, Lehtola J-M, Saari T, Hannonen S, Saveleva L, Kaartinen E,  Fernández Acosta F, Cruz-Haces M, Löppönen H, Mackay-Sim A, Kaikkonen MU,  Koivisto AM, Malm T, White AR, Giugno, Chew S, Kanninen KM. Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients . Cells . 2022 Feb 15;11(4):676. doi: 10.3390/cells11040676. 

      Lampinen R, Górová V, Avesani S, Liddell  J.R, Penttilä  E, Závodná  T, Krejčík  Z, Lehtola  J-M, Saari T, Kalapudas J, Hannonen S, Löppönen H, Topinka J, Koivisto A.M, White A.R, Giugno R, Kanninen K.M. Biometal Dyshomeostasis in Olfactory Mucosa of Alzheimer’s Disease Patients.  International Journal of Molecular Sciences. 2022 Apr 8;23(8):4123. doi:: 10.3390/ijms23084123.

    • Beneficial brain health effects of physical exercise​

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      • A project funded by the Sigrid Juselius foundation and the Academy of Finland
      • Even though aging and genetic predisposition are the major Alzheimer’s disease (AD)  risk factors, there are also lifestyle factors such as physical inactivity which exert a huge impact on the development of AD. 
      • The main goal of this project is to provide new understanding on the beneficial mechanisms induced by regular physical exercise both in the brain and periphery, in the context of AD. 
      • Understanding the cellular and molecular events associated with lifestyle modulation such as regular exercise will be highly important for limiting AD-related pathology via non-pharmacological strategy and promoting healthy aging.
      • Our results show that long-term voluntary exercise has beneficial against cognitive impairment developing in the 5xFAD mouse model of AD and this is associated with remodelling of glial cells – the astrocytes. 
      • Long-term voluntary exercise also modulates brain and peripheral iron metabolism, which is altered in AD. Our study was the first which link brain iron status with the reduction of iron regulator protein hepcidin in mice undergoing exercise. The results suggests that regular exercise regulates iron homeostasis decreasing hepcidin levels in the brain possibly via an attenuation of the interleukin-6 (IL-6)/STAT3 pathway.

       

      For more information, please see the following research articles: 

      Belaya I, Kucháriková N, Górová V, Kysenius K, Hare D J, Crouch P J, Malm T, Atalay M, White A R, Liddell JR, Kanninen KM. Regular physical exercise modulates iron homeostasis in the 5xFAD mouse model of Alzheimer’s disease. Int. J. Mol. Sci. 2021, 22 (16), 8715. https://doi.org/10.3390/ijms22168715

      Belaya I, Ivanova M, Sorvari A, Ilicic M, Loppi S, Koivisto H, Varricchio A, Tikkanen H, Walker FR, Atalay M, Malm T, Grubman A, Tanila H, Kanninen KM. Astrocyte remodeling in the beneficial effects of long-term voluntary exercise in Alzheimer’s disease. Journal of Neuroinflammation. 2020 Sep 15; 17: 271. https://doi.org/10.1186/s12974-020-01935-w

Group members - UEF