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Article: Sex-specific changes in protein expression of membrane transporters in the brain cortex of 5xFAD mouse model of Alzheimer's disease.

Puris, Elena / Saveleva, Liudmila / Auriola, Seppo / Gynther, Mikko / Kanninen, Katja M / Fricker, Gert

2024 Volume 15, Page(s) 1365051

Abstract: Membrane transporters playing an important role in the passage of drugs, metabolites and nutrients across the membranes of the brain cells have been shown to be involved in pathogenesis of Alzheimer's disease (AD). However, little is known about sex- ... ...

Abstract	Membrane transporters playing an important role in the passage of drugs, metabolites and nutrients across the membranes of the brain cells have been shown to be involved in pathogenesis of Alzheimer's disease (AD). However, little is known about sex-specific changes in transporter protein expression at the brain in AD. Here, we investigated sex-specific alterations in protein expression of three ATP-binding cassette (ABC) and five solute carriers (SLC) transporters in the prefrontal cortex of a commonly used model of familial AD (FAD), 5xFAD mice. Sensitive liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomic analysis was applied for absolute quantification of transporter protein expression. We compared the changes in transporter protein expressions in 7-month-old male and female 5xFAD mice versus sex-matched wild-type mice. The study revealed a significant sex-specific increase in protein expression of ABCC1 (
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2024.1365051
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Book ; Online: Metals and neurodegeneration: Restoring the balance

Crouch, Peter J. / Kanninen, Katja M. / White, Anthony R.

2016

Abstract: Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These biometals have important roles in the brain, driving cellular respiration, ... ...

Abstract	Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These biometals have important roles in the brain, driving cellular respiration, antioxidant activity, intracellular signaling and many additional structural and enzymatic functions. There is now considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer's, Parkinson's, prion and motor neuron diseases. Recent studies also support biometal roles in a number of less common neurodegenerative disorders. The role of biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. These approaches range from genetic manipulation of biometal transport to chelation of excess metals or delivery of metals where levels are deficient. A number of these approaches are offering promising results in cellular and animal models of neurodegeneration with successful translation to pre-clinical and clinical trials. At a time of aging populations and slow progress in development of neurotherapeutics to treat age-related neurodegenerative diseases, there is now a critical need to further our understanding of biometals in neurodegeneration. This issue covers a broad range of topics related to biometals and their role in neurodegeneration. It is hoped that this will inspire greater discussion and exchange of ideas in this crucial area of research and lead to positive outcomes for sufferers of these neurodegenerative diseases
Keywords	Neurosciences. Biological psychiatry. Neuropsychiatry ; Science (General)
Size	1 electronic resource (132 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020091167
ISBN	9782889197392 ; 2889197395
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Increased Expression of Transferrin Receptor 1 in the Brain Cortex of 5xFAD Mouse Model of Alzheimer's Disease Is Associated with Activation of HIF-1 Signaling Pathway.

Petralla, Sabrina / Saveleva, Liudmila / Kanninen, Katja M / Oster, Julia S / Panayotova, Maria / Fricker, Gert / Puris, Elena

Molecular neurobiology

2024

Abstract: Alzheimer's disease (AD) is the most common cause of dementia. Despite intensive research efforts, there are currently no effective treatments to cure and prevent AD. There is growing evidence that dysregulation of iron homeostasis may contribute to the ... ...

Abstract	Alzheimer's disease (AD) is the most common cause of dementia. Despite intensive research efforts, there are currently no effective treatments to cure and prevent AD. There is growing evidence that dysregulation of iron homeostasis may contribute to the pathogenesis of AD. Given the important role of the transferrin receptor 1 (TfR1) in regulating iron distribution in the brain, as well as in the drug delivery, we investigated its expression in the brain cortex and isolated brain microvessels from female 8-month-old 5xFAD mice mimicking advanced stage of AD. Moreover, we explored the association between the TfR1 expression and the activation of the HIF-1 signaling pathway, as well as oxidative stress and inflammation in 5xFAD mice. Finally, we studied the impact of Aβ
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-024-03990-3
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Article ; Online: Editorial: Air pollution and brain health.

White, Anthony / Kanninen, Katja / Malm, Tarja / Schins, Roel

Neurochemistry international

2020 Volume 141, Page(s) 104900

MeSH term(s)	Air Pollution/adverse effects ; Animals ; Brain/physiology ; Environmental Exposure ; Humans ; Particulate Matter
Chemical Substances	Particulate Matter
Language	English
Publishing date	2020-11-07
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/j.neuint.2020.104900
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Zs.A 1610: Show issues

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Article: The Interaction between Circulating Cell-Free Mitochondrial DNA and Inflammatory Cytokines in Predicting Human Mental Health Issue Risk in Adolescents: An Explorative Study.

Alatalo, Arto / de Sousa Maciel, Izaque / Kucháriková, Nina / Chew, Sweelin / van Kamp, Irene / Foraster, Maria / Julvez, Jordi / Kanninen, Katja M

Biomedicines

2023 Volume 11, Issue 3

Abstract: Adolescence is often a challenging time in which psychiatric issues have a strong connection to mental health disorders later in life. The early identification of the problems can reduce the burden of disease. To date, the effective identification of ... ...

Abstract	Adolescence is often a challenging time in which psychiatric issues have a strong connection to mental health disorders later in life. The early identification of the problems can reduce the burden of disease. To date, the effective identification of adolescents at risk of developing mental health problems remains understudied. Altogether, the interaction between circulating cell-free mtDNA (ccf-mtDNA) and inflammatory cytokines in adolescents is insufficiently understood regarding experienced mental health difficulties. Our study selected the participants based on the Strength and Difficulty Questionnaire (SDQ) score using the cut-off points of 3 and 18 for the low and the high score groups, respectively. The answers of the SDQ at the age of 12.2-15.7 years contributed to the investigation of (i) whether ccf-mtDNA units are associated with cytokines, and (ii) if an interaction model for predicting risk of mental health issues is observed. We discovered a sex-specific correlation between the screened markers associated with mental health problems in the low and high SDQ score groups among the male participants and in the low SDQ score group among the female participants. The mitochondrial
Language	English
Publishing date	2023-03-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11030818
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Article ; Online: Type-I interferons in Parkinson's disease: innate inflammatory response drives fate of neurons in model of degenerative brain disorder: An editorial comment on 'Type-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone'.

Kanninen, Katja M / White, Anthony R

Journal of neurochemistry

2017 Volume 141, Issue 1, Page(s) 9–11

Abstract: Read the commented article 'Type-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone' on page 75. ...

Abstract	Read the commented article 'Type-I interferons mediate the neuroinflammatory response and neurotoxicity induced by rotenone' on page 75.
MeSH term(s)	Humans ; Interferon Type I ; Neurons ; Neurotoxicity Syndromes ; Parkinson Disease ; Rotenone
Chemical Substances	Interferon Type I ; Rotenone (03L9OT429T)
Language	English
Publishing date	2017-02-24
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.13983
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Article ; Online: Particulate matter from car exhaust alters function of human iPSC-derived microglia.

Jäntti, Henna / Jonk, Steffi / Gómez Budia, Mireia / Ohtonen, Sohvi / Fagerlund, Ilkka / Fazaludeen, Mohammad Feroze / Aakko-Saksa, Päivi / Pebay, Alice / Lehtonen, Šárka / Koistinaho, Jari / Kanninen, Katja M / Jalava, Pasi I / Malm, Tarja / Korhonen, Paula

Particle and fibre toxicology

2024 Volume 21, Issue 1, Page(s) 6

Abstract: Background: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence ... ...

Abstract	Background: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. Results: Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml Conclusions: Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.
MeSH term(s)	Humans ; Particulate Matter/toxicity ; Particulate Matter/analysis ; Microglia/chemistry ; Induced Pluripotent Stem Cells/chemistry ; Automobiles ; Reactive Oxygen Species ; Vehicle Emissions/toxicity ; Vehicle Emissions/analysis ; Neurodegenerative Diseases
Chemical Substances	Particulate Matter ; Reactive Oxygen Species ; Vehicle Emissions
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2170936-1
ISSN	1743-8977 ; 1743-8977
ISSN (online)	1743-8977
ISSN	1743-8977
DOI	10.1186/s12989-024-00564-y
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Article ; Online: Proteomic insights into mental health status: plasma markers in young adults.

Afonin, Alexey M / Piironen, Aino-Kaisa / de Sousa Maciel, Izaque / Ivanova, Mariia / Alatalo, Arto / Whipp, Alyce M / Pulkkinen, Lea / Rose, Richard J / van Kamp, Irene / Kaprio, Jaakko / Kanninen, Katja M

Translational psychiatry

2024 Volume 14, Issue 1, Page(s) 55

Abstract: Global emphasis on enhancing prevention and treatment strategies necessitates an increased understanding of the biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental ... ...

Abstract	Global emphasis on enhancing prevention and treatment strategies necessitates an increased understanding of the biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the "general psychopathology factor", is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here, we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography-tandem mass spectrometry, 13 proteins with a significant connection with the p-factor were identified, 8 of which were linked to epidermal growth factor receptor (EGFR) signaling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.
MeSH term(s)	Humans ; Young Adult ; Proteomics ; Mental Disorders ; Psychopathology ; Chromatography, Liquid ; Health Status
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-024-02751-z
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Article ; Online: Upregulation of Integrin beta-3 in astrocytes upon Alzheimer's disease progression in the 5xFAD mouse model.

Ivanova, Mariia / Belaya, Irina / Kucháriková, Nina / de Sousa Maciel, Izaque / Saveleva, Liudmila / Alatalo, Arto / Juvonen, Ilona / Thind, Navjot / Andrès, Clarisse / Lampinen, Riikka / Chew, Sweelin / Kanninen, Katja M

Neurobiology of disease

2024 Volume 191, Page(s) 106410

Abstract: Integrins are receptors that have been linked to various brain disorders, including Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. While Integrin beta-3 (ITGB3) is known to participate in multiple cellular processes such as ... ...

Abstract	Integrins are receptors that have been linked to various brain disorders, including Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. While Integrin beta-3 (ITGB3) is known to participate in multiple cellular processes such as adhesion, migration, and signaling, its specific role in AD remains poorly understood, particularly in astrocytes, the main glial cell type in the brain. In this study, we investigated alterations in ITGB3 gene and protein expression during aging in different brain regions of the 5xFAD mouse model of AD and assessed the interplay between ITGB3 and astrocytes. Primary cultures from adult mouse brains were used to gain further insight into the connection between ITGB3 and amyloid beta (Aβ) in astrocytes. In vivo studies showed a correlation between ITGB3 and the astrocytic marker GFAP in the 5xFAD brains, indicating its association with reactive astrocytes. In vitro studies revealed increased gene expression of ITGB3 upon Aβ treatment. Our findings underscore the potential significance of ITGB3 in astrocyte reactivity in the context of Alzheimer's disease.
MeSH term(s)	Animals ; Mice ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Astrocytes/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Neuroglia/metabolism ; Up-Regulation
Chemical Substances	Amyloid beta-Peptides ; Itgb3 protein, mouse
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2024.106410
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Zs.A 4444: Show issues

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Article ; Online: Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection.

Shahbaz, Muhammad Ali / Kuivanen, Suvi / Mussalo, Laura / Afonin, Alexey M / Kumari, Kajal / Behzadpour, Donya / Kalapudas, Juho / Koivisto, Anne M / Penttilä, Elina / Löppönen, Heikki / Jalava, Pasi / Vapalahti, Olli / Balistreri, Giuseppe / Lampinen, Riikka / Kanninen, Katja M

Environmental research

2024 Volume 249, Page(s) 118451

Abstract: Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. ... ...

Abstract	Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. Furthermore, exposure to particulate matter (PM), an important constituent of air pollution, is linked to adverse effects on the brain, including cognitive decline and Alzheimer's disease (AD). The olfactory mucosa (OM), a tissue located at the rooftop of the nasal cavity, is directly exposed to inhaled air and in direct contact with the brain. Increasing evidence of OM dysfunction related to neuropathogenesis and viral infection demonstrates the importance of elucidating the interplay between viruses and air pollutants at the OM. This study examined the effects of subacute exposure to urban PM 0.2 and PM 10-2.5 on SARS-CoV-2 infection using primary human OM cells obtained from cognitively healthy individuals and individuals diagnosed with AD. OM cells were exposed to PM and subsequently infected with the SARS-CoV-2 virus in the presence of pollutants. SARS-CoV-2 entry receptors and replication, toxicological endpoints, cytokine release, oxidative stress markers, and amyloid beta levels were measured. Exposure to PM did not enhance the expression of viral entry receptors or cellular viral load in human OM cells. However, PM-exposed and SARS-CoV-2-infected cells showed alterations in cellular and immune responses when compared to cells infected only with the virus or pollutants. These changes are highly pronounced in AD OM cells. These results suggest that exposure of human OM cells to PM does not increase susceptibility to SARS-CoV-2 infection in vitro, but it can alter cellular immune responses to the virus, particularly in AD. Understanding the interplay of air pollutants and COVID-19 can provide important insight for the development of public health policies and interventions to reduce the negative influences of air pollution exposure.
MeSH term(s)	Particulate Matter/toxicity ; Humans ; Olfactory Mucosa/drug effects ; Olfactory Mucosa/virology ; COVID-19/immunology ; SARS-CoV-2 ; Air Pollutants/toxicity ; Aged ; Male ; Female ; Alzheimer Disease/immunology ; Alzheimer Disease/chemically induced ; Alzheimer Disease/virology ; Middle Aged ; Cytokines/metabolism ; Aged, 80 and over ; Oxidative Stress/drug effects
Chemical Substances	Particulate Matter ; Air Pollutants ; Cytokines
Language	English
Publishing date	2024-02-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2024.118451
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