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Article ; Online: Neurobiology and Changing Ecosystems: Mechanisms Underlying Responses to Human-Generated Environmental Impacts.

Anttonen, Tommi / Burghi, Thiago / Duvall, Laura / Fernandez, Maria P / Gutierrez, Gabrielle / Kermen, Florence / Merlin, Christine / Michaiel, Angie

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 45, Page(s) 7530–7537

Abstract: Human generated environmental change profoundly affects organisms that reside across diverse ecosystems. Although nervous systems evolved to flexibly sense, respond, and adapt to environmental change, it is unclear whether the rapid rate of environmental ...

Abstract	Human generated environmental change profoundly affects organisms that reside across diverse ecosystems. Although nervous systems evolved to flexibly sense, respond, and adapt to environmental change, it is unclear whether the rapid rate of environmental change outpaces the adaptive capacity of complex nervous systems. Here, we explore neural systems mediating responses to, or impacted by, changing environments, such as those induced by global heating, sensory pollution, and changing habitation zones. We focus on rising temperature and accelerated changes in environments that impact sensory experience as examples of perturbations that directly or indirectly impact neural function, respectively. We also explore a mechanism involved in cross-species interactions that arises from changing habitation zones. We demonstrate that anthropogenic influences on neurons, circuits, and behaviors are widespread across taxa and require further scientific investigation to understand principles underlying neural resilience to accelerating environmental change.
MeSH term(s)	Humans ; Ecosystem ; Neurobiology ; Neurons ; Temperature
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1431-23.2023
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Article: The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea.

Kirjavainen, Anna / Laos, Maarja / Anttonen, Tommi / Pirvola, Ulla

Biology open

2015 Volume 4, Issue 4, Page(s) 516–526

Abstract: Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic ...

Abstract	Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC), a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.
Language	English
Publishing date	2015-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2632264-X
ISSN	2046-6390
ISSN	2046-6390
DOI	10.1242/bio.20149753
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Article ; Online: Prevalence of temporomandibular disorders (TMD) among Finnish prisoners: cross-sectional clinical study.

Vainionpää, Raija / Kinnunen, Tommi / Pesonen, Paula / Laitala, Marja-Liisa / Anttonen, Vuokko / Sipilä, Kirsi

Acta odontologica Scandinavica

2018 Volume 77, Issue 4, Page(s) 264–268

Abstract: Objective: The aim of the present study was to evaluate the prevalence of self-reported temporomandibular disorders (TMD) symptoms and clinically diagnosed TMD among Finnish prisoners.: Material and methods: Altogether 100 prisoners from the Pelso ... ...

Abstract	Objective: The aim of the present study was to evaluate the prevalence of self-reported temporomandibular disorders (TMD) symptoms and clinically diagnosed TMD among Finnish prisoners. Material and methods: Altogether 100 prisoners from the Pelso Prison, Vaala, Finland, underwent dental and TMD clinical examinations performed by a calibrated and well-trained dentist. Symptom Questionnaire and clinical examination according to a Finnish pre-final version of the DC/TMD (Diagnostic Criteria for Temporomandibular Disorders) Axis I protocol were used to evaluate the prevalence of TMD sub-diagnoses. Results: The most common TMD symptoms were facial pain (54.0%), temporomandibular joint noises (43.0%) and headache (37.0%). The prevalence of joint-related TMD diagnoses was four and a half times higher than diagnoses attributed with pain (76.0% vs. 17.0%). The most common TMD diagnoses were degenerative joint disease (33.0%) and disc displacement with reduction (33.0%). Conclusions: The prevalence of self-reported TMD symptoms and clinical assessed TMD, especially join-related TMD diagnoses, is high among Finnish prisoners. Examination and treatment of TMD should become a common practice also in prison dental care.
MeSH term(s)	Cross-Sectional Studies ; Facial Pain/diagnosis ; Facial Pain/epidemiology ; Female ; Finland/epidemiology ; Headache/diagnosis ; Headache/epidemiology ; Health Status ; Humans ; Male ; Neurologic Examination/statistics & numerical data ; Physical Examination/statistics & numerical data ; Prevalence ; Prisoners/statistics & numerical data ; Prisons ; Temporomandibular Joint Disorders/diagnosis ; Temporomandibular Joint Disorders/epidemiology
Language	English
Publishing date	2018-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	210362-x
ISSN	1502-3850 ; 0001-6357
ISSN (online)	1502-3850
ISSN	0001-6357
DOI	10.1080/00016357.2018.1535660
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Article ; Online: The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

Anna Kirjavainen / Maarja Laos / Tommi Anttonen / Ulla Pirvola

Biology Open, Vol 4, Iss 4, Pp 516-

2015 Volume 526

Abstract	Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC), a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.
Keywords	Planar polarity ; Patterning ; Development ; Hair cell ; Stereociliary bundle ; Kinocilium ; Microtubules ; aPKC ; Auditory ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2015-03-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cytoskeletal Stability in the Auditory Organ

Anttonen, Tommi / Belevich, Ilya / Laos, Maarja / Herranen, Anni / Jokitalo, Eija / Brakebusch, Cord / Pirvola, Ulla

eNeuro

2017 Volume 4, Issue 5

Abstract: Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of ... ...

Abstract	Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice
MeSH term(s)	Actins/metabolism ; Age Factors ; Animals ; Animals, Newborn ; Cochlea/cytology ; Cochlea/embryology ; Cochlea/growth & development ; Cytoskeleton/metabolism ; Embryo, Mammalian ; Epithelium/embryology ; Epithelium/growth & development ; Epithelium/metabolism ; Epithelium/ultrastructure ; Female ; Gene Expression Regulation, Developmental/genetics ; Hair Cells, Vestibular/metabolism ; Hair Cells, Vestibular/ultrastructure ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Electron, Scanning ; Myosin Type II/metabolism ; Pregnancy ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Wound Healing/genetics ; rhoA GTP-Binding Protein/genetics ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	Actins ; Fgfr3 protein, mouse (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1) ; Myosin Type II (EC 3.6.1.-) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2017-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0149-17.2017
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Article ; Online: Macromolecular and electrical coupling between inner hair cells in the rodent cochlea.

Jean, Philippe / Anttonen, Tommi / Michanski, Susann / de Diego, Antonio M G / Steyer, Anna M / Neef, Andreas / Oestreicher, David / Kroll, Jana / Nardis, Christos / Pangršič, Tina / Möbius, Wiebke / Ashmore, Jonathan / Wichmann, Carolin / Moser, Tobias

Nature communications

2020 Volume 11, Issue 1, Page(s) 3208

Abstract: Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from ... ...

Abstract	Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in 'mini-syncytia'. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca
MeSH term(s)	Animals ; Calcium Signaling ; Cochlea/cytology ; Cochlea/innervation ; Cochlear Nerve/metabolism ; Electron Microscope Tomography ; Giant Cells ; Hair Cells, Auditory, Inner/cytology ; Hair Cells, Auditory, Inner/physiology ; Hearing/physiology ; Mice ; Patch-Clamp Techniques ; Rodentia/physiology ; Synapses/metabolism
Language	English
Publishing date	2020-06-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-17003-z
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Article ; Online: Macromolecular and electrical coupling between inner hair cells in the rodent cochlea

Philippe Jean / Tommi Anttonen / Susann Michanski / Antonio M. G. de Diego / Anna M. Steyer / Andreas Neef / David Oestreicher / Jana Kroll / Christos Nardis / Tina Pangršič / Wiebke Möbius / Jonathan Ashmore / Carolin Wichmann / Tobias Moser

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 14

Abstract: The inner hair cells (IHCs) within the cochlea convey sound information and have been thought to be electrically and metabolically independent from each other. Here authors report that a subset of IHCs are electrochemically coupled in ‘mini-syncytia’. ...

Abstract	The inner hair cells (IHCs) within the cochlea convey sound information and have been thought to be electrically and metabolically independent from each other. Here authors report that a subset of IHCs are electrochemically coupled in ‘mini-syncytia’.
Keywords	Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Macromolecular and electrical coupling between inner hair cells in the rodent cochlea

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 14

Abstract	The inner hair cells (IHCs) within the cochlea convey sound information and have been thought to be electrically and metabolically independent from each other. Here authors report that a subset of IHCs are electrochemically coupled in ‘mini-syncytia’.
Keywords	Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells.

Laos, Maarja / Anttonen, Tommi / Kirjavainen, Anna / af Hällström, Taija / Laiho, Marikki / Pirvola, Ulla

Aging

2014 Volume 6, Issue 6, Page(s) 496–510

Abstract: Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs hold promise as a platform for therapeutic regeneration of the sensory hair cells. Prior data have shown proliferative restrictions of adult SCs forced to re-enter the cell ...

Abstract	Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs hold promise as a platform for therapeutic regeneration of the sensory hair cells. Prior data have shown proliferative restrictions of adult SCs forced to re-enter the cell cycle. By comparing juvenile and adult SCs in explant cultures, we have here studied how proliferative restrictions are linked with DNA damage signaling. Cyclin D1 overexpression, used to stimulate cell cycle re-entry, triggered higher proliferative activity of juvenile SCs. Phosphorylated form of histone H2AX (γH2AX) and p53 binding protein 1 (53BP1) were induced in a foci-like pattern in SCs of both ages as an indication of DNA double-strand break formation and activated DNA damage response. Compared to juvenile SCs, γH2AX and the repair protein Rad51 were resolved with slower kinetics in adult SCs, accompanied by increased apoptosis. Consistent with thein vitro data, in a Rb mutant mouse model in vivo, cell cycle re-entry of SCs was associated with γH2AX foci induction. In contrast to cell cycle reactivation, pharmacological stimulation of SC-to-hair-cell transdifferentiation in vitro did not trigger γH2AX. Thus, DNA damage and its prolonged resolution are critical barriers in the efforts to stimulate proliferation of the adult inner ear SCs.
MeSH term(s)	Adult Stem Cells/cytology ; Animals ; Cell Proliferation/physiology ; DNA Damage/physiology ; Labyrinth Supporting Cells/cytology ; Mice ; Organ Culture Techniques ; Signal Transduction/physiology
Language	English
Publishing date	2014-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.100668
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Article ; Online: How to bury the dead: elimination of apoptotic hair cells from the hearing organ of the mouse.

Anttonen, Tommi / Belevich, Ilya / Kirjavainen, Anna / Laos, Maarja / Brakebusch, Cord / Jokitalo, Eija / Pirvola, Ulla

Journal of the Association for Research in Otolaryngology : JARO

2014 Volume 15, Issue 6, Page(s) 975–992

Abstract: Hair cell death is a major cause of hearing impairment. Preservation of surface barrier upon hair cell loss is critical to prevent leakage of potassium-rich endolymph into the organ of Corti and to prevent expansion of cellular damage. Understanding of ... ...

Abstract	Hair cell death is a major cause of hearing impairment. Preservation of surface barrier upon hair cell loss is critical to prevent leakage of potassium-rich endolymph into the organ of Corti and to prevent expansion of cellular damage. Understanding of wound healing in this cytoarchitecturally complex organ requires ultrastructural 3D visualization. Powered by the serial block-face scanning electron microscopy, we penetrate into the cell biological mechanisms in the acute response of outer hair cells and glial-like Deiters' cells to ototoxic trauma in vivo. We show that Deiters' cells function as phagocytes. Upon trauma, their phalangeal processes swell and the resulting close cellular contacts allow engulfment of apoptotic cell debris. Apical domains of dying hair cells are eliminated from the inner ear sensory epithelia, an event thought to depend on supporting cells' actomyosin contractile activity. We show that in the case of apoptotic outer hair cells of the organ of Corti, elimination of their apices is preceded by strong cell body shrinkage, emphasizing the role of the dying cell itself in the cleavage. Our data reveal that the resealing of epithelial surface by junctional extensions of Deiters' cells is dynamically reinforced by newly polymerized F-actin belts. By analyzing Cdc42-inactivated Deiters' cells with defects in actin dynamics and surface closure, we show that compromised barrier integrity shifts hair cell death from apoptosis to necrosis and leads to expanded hair cell and nerve fiber damage. Our results have implications concerning therapeutic protective and regenerative interventions, because both interventions should maintain barrier integrity.
MeSH term(s)	Actins/metabolism ; Animals ; Apoptosis ; Female ; Male ; Mice ; Microscopy, Electron, Scanning ; Organ of Corti/physiology ; Organ of Corti/ultrastructure ; Phagocytosis ; Wound Healing
Chemical Substances	Actins
Language	English
Publishing date	2014-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2021417-0
ISSN	1438-7573 ; 1525-3961
ISSN (online)	1438-7573
ISSN	1525-3961
DOI	10.1007/s10162-014-0480-x
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