The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations

The progression of neurodegenerative diseases is reciprocally associated with impairments in peripheral immune responses. We investigated different contexts of selective neurodegeneration to identify specific alterations of peripheral immune cells and, at the same time, discover potential biomarkers...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Carlos del Pilar, Rafael Lebrón-Galán, Ester Pérez-Martín, Laura Pérez-Revuelta, Carmelo Antonio Ávila-Zarza, José Ramón Alonso, Diego Clemente, Eduardo Weruaga, David Díaz
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://doaj.org/article/1971fdd4f2dc4269806dea73b2b40141
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:1971fdd4f2dc4269806dea73b2b40141
record_format dspace
spelling oai:doaj.org-article:1971fdd4f2dc4269806dea73b2b401412021-12-01T19:23:22ZThe Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations1662-510210.3389/fncel.2021.773696https://doaj.org/article/1971fdd4f2dc4269806dea73b2b401412021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.773696/fullhttps://doaj.org/toc/1662-5102The progression of neurodegenerative diseases is reciprocally associated with impairments in peripheral immune responses. We investigated different contexts of selective neurodegeneration to identify specific alterations of peripheral immune cells and, at the same time, discover potential biomarkers associated to this pathological condition. Consequently, a model of human cerebellar degeneration and ataxia -the Purkinje Cell Degeneration (PCD) mouse- has been employed, as it allows the study of different processes of selective neuronal death in the same animal, i.e., Purkinje cells in the cerebellum and mitral cells in the olfactory bulb. Infiltrated leukocytes were studied in both brain areas and compared with those from other standardized neuroinflammatory models obtained by administering either gamma radiation or lipopolysaccharide. Moreover, both myeloid and lymphoid splenic populations were analyzed by flow cytometry, focusing on markers of functional maturity and antigen presentation. The severity and type of neural damage and inflammation affected immune cell infiltration. Leukocytes were more numerous in the cerebellum of PCD mice, being located predominantly within those cerebellar layers mostly affected by neurodegeneration, in a completely different manner than the typical models of induced neuroinflammation. Furthermore, the milder degeneration of the olfactory bulb did not foster leukocyte attraction. Concerning the splenic analysis, in PCD mice we found: (1) a decreased percentage of several myeloid cell subsets, and (2) a reduced mean fluorescence intensity in those myeloid markers related to both antigen presentation and functional maturity. In conclusion, the selective degeneration of Purkinje cells triggers a specific effect on peripheral immune cells, fostering both attraction and functional changes. This fact endorses the employment of peripheral immune cell populations as concrete biomarkers for monitoring different neuronal death processes.Carlos del PilarCarlos del PilarRafael Lebrón-GalánRafael Lebrón-GalánEster Pérez-MartínEster Pérez-MartínLaura Pérez-RevueltaLaura Pérez-RevueltaCarmelo Antonio Ávila-ZarzaCarmelo Antonio Ávila-ZarzaJosé Ramón AlonsoJosé Ramón AlonsoJosé Ramón AlonsoDiego ClementeDiego ClementeEduardo WeruagaEduardo WeruagaDavid DíazDavid DíazFrontiers Media S.A.articleselective neurodegenerationneuroinflammationbrain infiltrationbiomarkersperipheral immune alterationsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution DOAJ
collection DOAJ
language EN
topic selective neurodegeneration
neuroinflammation
brain infiltration
biomarkers
peripheral immune alterations
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle selective neurodegeneration
neuroinflammation
brain infiltration
biomarkers
peripheral immune alterations
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Carlos del Pilar
Carlos del Pilar
Rafael Lebrón-Galán
Rafael Lebrón-Galán
Ester Pérez-Martín
Ester Pérez-Martín
Laura Pérez-Revuelta
Laura Pérez-Revuelta
Carmelo Antonio Ávila-Zarza
Carmelo Antonio Ávila-Zarza
José Ramón Alonso
José Ramón Alonso
José Ramón Alonso
Diego Clemente
Diego Clemente
Eduardo Weruaga
Eduardo Weruaga
David Díaz
David Díaz
The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
description The progression of neurodegenerative diseases is reciprocally associated with impairments in peripheral immune responses. We investigated different contexts of selective neurodegeneration to identify specific alterations of peripheral immune cells and, at the same time, discover potential biomarkers associated to this pathological condition. Consequently, a model of human cerebellar degeneration and ataxia -the Purkinje Cell Degeneration (PCD) mouse- has been employed, as it allows the study of different processes of selective neuronal death in the same animal, i.e., Purkinje cells in the cerebellum and mitral cells in the olfactory bulb. Infiltrated leukocytes were studied in both brain areas and compared with those from other standardized neuroinflammatory models obtained by administering either gamma radiation or lipopolysaccharide. Moreover, both myeloid and lymphoid splenic populations were analyzed by flow cytometry, focusing on markers of functional maturity and antigen presentation. The severity and type of neural damage and inflammation affected immune cell infiltration. Leukocytes were more numerous in the cerebellum of PCD mice, being located predominantly within those cerebellar layers mostly affected by neurodegeneration, in a completely different manner than the typical models of induced neuroinflammation. Furthermore, the milder degeneration of the olfactory bulb did not foster leukocyte attraction. Concerning the splenic analysis, in PCD mice we found: (1) a decreased percentage of several myeloid cell subsets, and (2) a reduced mean fluorescence intensity in those myeloid markers related to both antigen presentation and functional maturity. In conclusion, the selective degeneration of Purkinje cells triggers a specific effect on peripheral immune cells, fostering both attraction and functional changes. This fact endorses the employment of peripheral immune cell populations as concrete biomarkers for monitoring different neuronal death processes.
format article
author Carlos del Pilar
Carlos del Pilar
Rafael Lebrón-Galán
Rafael Lebrón-Galán
Ester Pérez-Martín
Ester Pérez-Martín
Laura Pérez-Revuelta
Laura Pérez-Revuelta
Carmelo Antonio Ávila-Zarza
Carmelo Antonio Ávila-Zarza
José Ramón Alonso
José Ramón Alonso
José Ramón Alonso
Diego Clemente
Diego Clemente
Eduardo Weruaga
Eduardo Weruaga
David Díaz
David Díaz
author_facet Carlos del Pilar
Carlos del Pilar
Rafael Lebrón-Galán
Rafael Lebrón-Galán
Ester Pérez-Martín
Ester Pérez-Martín
Laura Pérez-Revuelta
Laura Pérez-Revuelta
Carmelo Antonio Ávila-Zarza
Carmelo Antonio Ávila-Zarza
José Ramón Alonso
José Ramón Alonso
José Ramón Alonso
Diego Clemente
Diego Clemente
Eduardo Weruaga
Eduardo Weruaga
David Díaz
David Díaz
author_sort Carlos del Pilar
title The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
title_short The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
title_full The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
title_fullStr The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
title_full_unstemmed The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations
title_sort selective loss of purkinje cells induces specific peripheral immune alterations
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/1971fdd4f2dc4269806dea73b2b40141
work_keys_str_mv AT carlosdelpilar theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carlosdelpilar theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT rafaellebrongalan theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT rafaellebrongalan theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT esterperezmartin theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT esterperezmartin theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT lauraperezrevuelta theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT lauraperezrevuelta theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carmeloantonioavilazarza theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carmeloantonioavilazarza theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT diegoclemente theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT diegoclemente theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT eduardoweruaga theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT eduardoweruaga theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT daviddiaz theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT daviddiaz theselectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carlosdelpilar selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carlosdelpilar selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT rafaellebrongalan selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT rafaellebrongalan selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT esterperezmartin selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT esterperezmartin selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT lauraperezrevuelta selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT lauraperezrevuelta selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carmeloantonioavilazarza selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT carmeloantonioavilazarza selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT joseramonalonso selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT diegoclemente selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT diegoclemente selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT eduardoweruaga selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT eduardoweruaga selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT daviddiaz selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
AT daviddiaz selectivelossofpurkinjecellsinducesspecificperipheralimmunealterations
_version_ 1718404617802350592