Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model.
<h4>Background</h4>Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial A...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/6175a1e168434618a83a7235ab39cfe0 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:6175a1e168434618a83a7235ab39cfe0 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:6175a1e168434618a83a7235ab39cfe02021-11-18T07:53:44ZAntipurinergic therapy corrects the autism-like features in the poly(IC) mouse model.1932-620310.1371/journal.pone.0057380https://doaj.org/article/6175a1e168434618a83a7235ab39cfe02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516405/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines-signaling molecules made in mitochondria-that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.<h4>Objectives and methods</h4>We used the maternal immune activation (MIA) mouse model of gestational poly(IC) exposure and treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.<h4>Results</h4>We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.<h4>Conclusions</h4>Hyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development.Robert K NaviauxZarazuela ZolkipliLin WangTomohiro NakayamaJane C NaviauxThuy P LeMichael A SchuchbauerMihael RogacQingbo TangLaura L DuganSusan B PowellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e57380 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Robert K Naviaux Zarazuela Zolkipli Lin Wang Tomohiro Nakayama Jane C Naviaux Thuy P Le Michael A Schuchbauer Mihael Rogac Qingbo Tang Laura L Dugan Susan B Powell Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| description |
<h4>Background</h4>Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines-signaling molecules made in mitochondria-that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.<h4>Objectives and methods</h4>We used the maternal immune activation (MIA) mouse model of gestational poly(IC) exposure and treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.<h4>Results</h4>We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.<h4>Conclusions</h4>Hyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development. |
| format |
article |
| author |
Robert K Naviaux Zarazuela Zolkipli Lin Wang Tomohiro Nakayama Jane C Naviaux Thuy P Le Michael A Schuchbauer Mihael Rogac Qingbo Tang Laura L Dugan Susan B Powell |
| author_facet |
Robert K Naviaux Zarazuela Zolkipli Lin Wang Tomohiro Nakayama Jane C Naviaux Thuy P Le Michael A Schuchbauer Mihael Rogac Qingbo Tang Laura L Dugan Susan B Powell |
| author_sort |
Robert K Naviaux |
| title |
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| title_short |
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| title_full |
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| title_fullStr |
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| title_full_unstemmed |
Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. |
| title_sort |
antipurinergic therapy corrects the autism-like features in the poly(ic) mouse model. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/6175a1e168434618a83a7235ab39cfe0 |
| work_keys_str_mv |
AT robertknaviaux antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT zarazuelazolkipli antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT linwang antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT tomohironakayama antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT janecnaviaux antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT thuyple antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT michaelaschuchbauer antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT mihaelrogac antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT qingbotang antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT lauraldugan antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel AT susanbpowell antipurinergictherapycorrectstheautismlikefeaturesinthepolyicmousemodel |
| _version_ |
1718422782656643072 |