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Chronic stress disrupts the homeostasis and progeny progression of oligodendroglial lineage cells, associating immune oligodendrocytes with prefrontal cortex hypomyelination.
Kokkosis, Alexandros G; Madeira, Miguel M; Mullahy, Matthew R; Tsirka, Stella E.
Afiliação
  • Kokkosis AG; Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794-8651, USA.
  • Madeira MM; Regeneron Genetic Center, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA.
  • Mullahy MR; Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794-8651, USA.
  • Tsirka SE; Department of Pharmacological Sciences, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, 11794-8651, USA.
Mol Psychiatry ; 27(6): 2833-2848, 2022 06.
Article em En | MEDLINE | ID: mdl-35301426
Major depressive disorder (MDD) is a chronic debilitating illness affecting yearly 300 million people worldwide. Oligodendrocyte-lineage cells have emerged as important neuromodulators in synaptic plasticity and crucial components of MDD pathophysiology. Using the repeated social defeat (RSDS) mouse model, we demonstrate that chronic psychosocial stress induces long-lasting losses and transient proliferation of oligodendrocyte-precursor cells (OPCs), aberrant differentiation into oligodendrocytes, and severe hypomyelination in the prefrontal cortex. Exposure to chronic stress results in OPC morphological impairments, excessive oxidative stress, and oligodendroglial apoptosis, implicating integrative-stress responses in depression. Analysis of single-nucleus transcriptomic data from MDD patients revealed oligodendroglial-lineage dysregulation and the presence of immune-oligodendrocytes (Im-OL), a novel population of cells with immune properties and myelination deficits. Im-OL were also identified in mice after RSDS, where oligodendrocyte-lineage cells expressed immune-related markers. Our findings demonstrate cellular and molecular changes in the oligodendroglial lineage in response to chronic stress and associate hypomyelination with Im-OL emergence during depression.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Depressivo Maior / Bainha de Mielina Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Depressivo Maior / Bainha de Mielina Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos