Mitochondrial spongiotic brain disease: astrocytic stress and harmful rapamycin and ketosis effect.

ABSTRACT: Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a group of severe, tissue-specific diseases of childhood with unknown pathogenesis. Brain-specific MDS manifests as devastating spongiotic encephalopathy with no curative therapy. Here, we report cell type-specific stress responses and effects of rapamycin treatment and ketogenic diet (KD) in mice with spongiotic encephalopathy mimicking human MDS, as these interventions were reported to improve some mitochondrial disease signs or symptoms. These mice with astrocyte-specific knockout of Twnk gene encoding replicative mtDNA helicase Twinkle (TwKO^astro) show wide-spread cell-autonomous astrocyte activation and mitochondrial integrated stress response (ISR^mt) induction with major metabolic remodeling of the bra

SUBMITTER: Ignatenko O 

PROVIDER: S-EPMC7409372 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature