Altered subcellular distribution of the 75-kDa DISC1 Isoform, cAMP accumulation, and decreased neuronal migration in schizophrenia and bipolar disorder: Implications for neurodevelopment

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dc.contributor.affiliationDepartment of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexicoes_ES
dc.contributor.emailimeza@cinvestav.mxes_ES
dc.creatorMuñoz-Estrada, Jesús
dc.creatorBenítez-King, Gloria
dc.creatorBerlanga, Carlos
dc.creatorMeza, Isaura
dc.creator.identificadorhttp://orcid.org/orcid.org/orcid.org/0000-0003-0959-6851>Benítez King, Gloriaes_ES
dc.date.accessioned2017-06-29T03:41:20Z
dc.date.accessioned2026-03-27T14:33:11Z
dc.date.available2017-06-29T03:41:20Z
dc.date.issued2015es_ES
dc.date.published2015es_ES
dc.description.abstractotrodiomaBACKGROUND: DISC1 (Disrupted-In-Schizophrenia-1) is considered a genetic risk factor for schizophrenia (SZ) and bipolar disorder (BD). DISC1 regulates microtubule stability, migration, and cAMP signaling in mammalian cell lines and mouse brain tissue. cAMP is a regulator of microtubule organization and migration in neurons. Aberrant microtubule organization has been observed in olfactory neuronal precursors (ONP) derived from patients with SZ and BD, which suggests involvement of DISC1 and cAMP. However, the biology of DISC1 in the physiopathology of psychiatric conditions remains elusive. AIMS: Herein, utilizing ONP obtained from SZ, BD patients and healthy subjects, we have studied DISC1 expression, protein levels, and subcellulardistribution by qRT-PCR, immunoblotting, subcellular fractionation, and confocal microscopy. Cell migration and cAMP accumulation were assessed by Transwell and PKA competition assays. RESULTS: We found increased levels of the 75-kDa DISC1 isoform in total cell extracts of ONP from patients with SZ and BD compared with controls. Subcellular distribution showed a significant decrease of cytoplasmic DISC1 concomitant with its augmented levels in transcription sites. Moreover, significant cAMP accumulation and diminished migration were also observed in patients' cells. CONCLUSION: Alterations of DISC1 levels and its cellular distribution, which negatively modify cAMP homeostasis, microtubule organization, and cell migration, in ONP from patients with SZ and BD, suggest that their presence in early stages of brain development may impact brain maturation and function.es_ES
dc.description.monthMayes_ES
dc.identifier2530es_ES
dc.identifier.citationJuan Carlos Bautista Ramírezes_ES
dc.identifier.doi 10.1111/cns.12377es_ES
dc.identifier.eissn1755-5949es_ES
dc.identifier.issn1755-5930es_ES
dc.identifier.numero5es_ES
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñizes_ES
dc.identifier.paginacion446-453es_ES
dc.identifier.placeInglaterraes_ES
dc.identifier.urihttps://doi.org/10.1111/cns.12377es_ES
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495214/es_ES
dc.identifier.urihttps://repositorio.inprf.gob.mx/handle/123456789/4379
dc.identifier.volumen21es_ES
dc.language.isoenges_ES
dc.publisherWiley-Blackwelles_ES
dc.relation21(5):446-453es_ES
dc.relation.jnabreviadoCNS NEUROSCI THERes_ES
dc.relation.journalCNS Neuroscience and Therapeuticses_ES
dc.rightsAcceso Cerradoes_ES
dc.subject.kwBipolar disorder
dc.subject.kwDISC1
dc.subject.kwMicrotubules
dc.subject.kwNeuronal migration
dc.subject.kwSchizophrenia
dc.titleAltered subcellular distribution of the 75-kDa DISC1 Isoform, cAMP accumulation, and decreased neuronal migration in schizophrenia and bipolar disorder: Implications for neurodevelopmentes_ES
dc.typeArtículoes_ES

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