Microglial Acid Sensing Regulates Carbon Dioxide-Evoked Fear

Página do item simplificado
dc.contributor.authorVollmer, Lauren Larke
dc.contributor.authorGhosal, Sriparna
dc.contributor.authorMcGuire, Jennifer L.
dc.contributor.authorAhlbrand, Rebecca L.
dc.contributor.authorLi, Ke-Yong
dc.contributor.authorSantin, Joseph M.
dc.contributor.authorRatliff-Rang, Christine A.
dc.contributor.authorPatrone, Luis G. A. [UNESP]
dc.contributor.authorRush, Jennifer
dc.contributor.authorLewkowich, Ian P.
dc.contributor.authorHerman, James P.
dc.contributor.authorPutnam, Robert W.
dc.contributor.authorSah, Renu
dc.contributor.institutionUniv Cincinnati
dc.contributor.institutionWright State Univ
dc.contributor.institutionChildrens Hosp Med Ctr
dc.contributor.institutionVet Affairs VA Med Ctr
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-11-26T17:06:27Z
dc.date.available2018-11-26T17:06:27Z
dc.date.issued2016-10-01
dc.description.abstractBACKGROUND: Carbon dioxide (CO2) inhalation, a biological challenge and pathologic marker in panic disorder, evokes intense fear and panic attacks in susceptible individuals. The molecular identity and anatomic location of CO2-sensing systems that translate CO2-evoked fear remain unclear. We investigated contributions of microglial acid sensor T cell death-associated gene-8 (TDAG8) and microglial proinflammatory responses in CO2-evoked behavioral and physiological responses. METHODS: CO2-evoked freezing, autonomic, and respiratory responses were assessed in TDAG8-deficient ((-/-)) and wild-type (1/1) mice. Involvement of TDAG8-dependent microglial activation and proinflammatory cytokine interleukin (IL)-1 beta with CO2-evoked responses was investigated using microglial blocker, minocycline, and IL-1 beta antagonist IL-1RA. CO2-chemosensitive firing responses using single-cell patch clamping were measured in TDAG8(-/-) and TDAG8(+/+) mice to gain functional insights. RESULTS: TDAG8 expression was localized in microglia enriched within the sensory circumventricular organs. TDAG8(-/-) mice displayed attenuated CO2-evoked freezing and sympathetic responses. TDAG8 deficiency was associated with reduced microglial activation and proinflammatory cytokine IL-1 beta within the subfornical organ. Central infusion of microglial activation blocker minocycline and IL-1 beta antagonist IL-1RA attenuated CO2-evoked freezing. Finally, CO2-evoked neuronal firing in patch-clamped subfornical organ neurons was dependent on acid sensor TDAG8 and IL-1 beta. CONCLUSIONS: Our data identify TDAG8-dependent microglial acid sensing as a unique chemosensor for detecting and translating hypercapnia to fear-associated behavioral and physiological responses, providing a novel mechanism for homeostatic threat detection of relevance to psychiatric conditions such as panic disorder.en
dc.description.affiliationUniv Cincinnati, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA
dc.description.affiliationUniv Cincinnati, Grad Program Neurosci, Cincinnati, OH USA
dc.description.affiliationWright State Univ, Dept Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA
dc.description.affiliationWright State Univ, Dept Biol Sci, Dayton, OH 45435 USA
dc.description.affiliationChildrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH USA
dc.description.affiliationVet Affairs VA Med Ctr, Cincinnati, OH USA
dc.description.affiliationSao Paulo State Univ, FCAV, Dept Anim Morphol & Physiol, Jaboticabal, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, FCAV, Dept Anim Morphol & Physiol, Jaboticabal, SP, Brazil
dc.description.sponsorshipNational Institute of Mental Health
dc.description.sponsorshipIdNational Institute of Mental Health: R01-MH093362
dc.description.sponsorshipIdNational Institute of Mental Health: R21MH083213
dc.format.extent541-551
dc.identifierhttp://dx.doi.org/10.1016/j.biopsych.2016.04.022
dc.identifier.citationBiological Psychiatry. New York: Elsevier Science Inc, v. 80, n. 7, p. 541-551, 2016.
dc.identifier.doi10.1016/j.biopsych.2016.04.022
dc.identifier.fileWOS000384741600014.pdf
dc.identifier.issn0006-3223
dc.identifier.urihttp://hdl.handle.net/11449/161997
dc.identifier.wosWOS:000384741600014
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiological Psychiatry
dc.relation.ispartofsjr5,490
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectAcid sensing
dc.subjectCarbon dioxide
dc.subjectFear
dc.subjectMicroglia
dc.subjectPanic
dc.subjectTDAG8
dc.titleMicroglial Acid Sensing Regulates Carbon Dioxide-Evoked Fearen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.orcid0000-0003-4471-6230[2]

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000384741600014.pdf
Tamanho:
3.08 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar

Coleções

Artigos - Morfologia e Fisiologia Animal - FCAV