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Amyloid precursor protein induces reactive astrogliosis.
Velezmoro Jauregui, Gretsen; Vukic, Dragana; Onyango, Isaac G; Arias, Carlos; Novotný, Jan S; Texlová, Katerina; Wang, Shanshan; Kovacovicova, Kristina Locker; Polakova, Natalie; Zelinkova, Jana; Carna, Maria; Lacovich, Valentina; Head, Brian P; Havas, Daniel; Mistrik, Martin; Zorec, Robert; Verkhratsky, Alexei; Keegan, Liam; O'Connell, Mary A; Rissman, Robert; Stokin, Gorazd B.
Afiliación
  • Velezmoro Jauregui G; Translational Ageing and Neuroscience Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
  • Vukic D; Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • Onyango IG; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
  • Arias C; Faculty of Science, National Centre for Biomedical Research, Masaryk University, Brno, Czech Republic.
  • Novotný JS; Translational Ageing and Neuroscience Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
  • Texlová K; Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
  • Wang S; Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Olomouc, Czech Republic.
  • Kovacovicova KL; Translational Ageing and Neuroscience Program, Centre for Translational Medicine, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
  • Polakova N; Veterans Affairs San Diego Healthcare System, San Diego, USA.
  • Zelinkova J; Department of Anesthesia, University of California San Diego, La Jolla, California, USA.
  • Carna M; PsychoGenics, Paramus, New Jersey, USA.
  • Lacovich V; Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Olomouc, Czech Republic.
  • Head BP; Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Olomouc, Czech Republic.
  • Havas D; Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Olomouc, Czech Republic.
  • Mistrik M; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
  • Zorec R; Veterans Affairs San Diego Healthcare System, San Diego, USA.
  • Verkhratsky A; Department of Anesthesia, University of California San Diego, La Jolla, California, USA.
  • Keegan L; PsychoGenics, Paramus, New Jersey, USA.
  • O'Connell MA; Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacky University Olomouc, Olomouc, Czech Republic.
  • Rissman R; Laboratory of Neuroendocrinology, Molecular Cell Physiology, Faculty of Medicine, Institute of Pathophysiology, University of Ljubljana, Ljubljana, Slovenia.
  • Stokin GB; Celica Biomedical, Technology Park, Ljubljana, Slovenia.
Acta Physiol (Oxf) ; 240(6): e14142, 2024 06.
Article en En | MEDLINE | ID: mdl-38584589
ABSTRACT

AIM:

Astrocytes respond to stressors by acquiring a reactive state characterized by changes in their morphology and function. Molecules underlying reactive astrogliosis, however, remain largely unknown. Given that several studies observed increase in the Amyloid Precursor Protein (APP) in reactive astrocytes, we here test whether APP plays a role in reactive astrogliosis.

METHODS:

We investigated whether APP instigates reactive astroglios by examining in vitro and in vivo the morphology and function of naive and APP-deficient astrocytes in response to APP and well-established stressors.

RESULTS:

Overexpression of APP in cultured astrocytes led to remodeling of the intermediate filament network, enhancement of cytokine production, and activation of cellular programs centered around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion abrogated remodeling of the intermediate filament network and blunted expression of IFN-stimulated gene products in response to lipopolysaccharide. Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein observed canonically in astrocytes in response to TBI.

CONCLUSIONS:

The APP thus represents a candidate molecular inducer and regulator of reactive astrogliosis. This finding has implications for understanding pathophysiology of neurodegenerative and other diseases of the nervous system characterized by reactive astrogliosis and opens potential new therapeutic avenues targeting APP and its pathways to modulate reactive astrogliosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Precursor de Proteína beta-Amiloide / Gliosis Límite: Animals Idioma: En Revista: Acta Physiol (Oxf) Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Astrocitos / Precursor de Proteína beta-Amiloide / Gliosis Límite: Animals Idioma: En Revista: Acta Physiol (Oxf) Asunto de la revista: FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido