Maternal immune activation during pregnancy alters the expression of mitochondrial dynamics markers in the brain of rat offspring

• Autorzy: Zawadzka A. , Cieslik M. , Gewartowska M. , Frontczak-Baniewicz M. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Prenatal exposure to infection and subsequent inflammatory responses, as well as, mitochondrial dysfunction has been implicated in the pathogenesis of autism spectrum disorders (ASDs). However, the molecular links between infection-induced fetal brain changes, mitochondrial deregulation, and the autistic phenotype remain obscure. AIM(S): Analysis of maternal immune activation (MIA)-induced changes in the expression of mitochondrial dynamics markers in the brain of the neonatal and adolescent rat offspring. METHOD(S): The MIA model was induced by single intraperitoneal injection of lipopolysaccharide (100 μg/kg b.w.) to pregnant rats at embryonic day 9.5. On the 7th or 52-53rd post-natal day, rat offspring were decapitated, and the brains isolated. Transmission electron microscopy (TEM), quantitative real‑time PCR (qPCR), and immunoblotting were used to determine mitochondrial ultrastructure and mRNA/protein expression, respectively. RESULTS: The electron microscopic study demonstrated altered mitochondrial morphology, including fragmented cristae, expanded matrix compartment, and membrane disruption in both the cerebral cortex and hippocampus of adolescent MIA offspring. Moreover, changes were noted in the expression of proteins involved in the maintenance of mitochondrial morphology. We observed upregulated fusion machinery proteins – mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and Opa1 – as well as mitochondrial fission proteins – dynamin related protein‑1 (Drp1) and fission protein 1 (Fis1) – in the neonatal MIA brains. However, in adolescent animals exposed to prenatal infection, the expression of Mfn1, Mfn2 and Opa1 was significantly reduced; nevertheless, Drp1 and Fis1 remained increased CONCLUSIONS: MIA-evoked perturbations in the proteins regulating mitochondrial dynamics reveal potentially important aspects of the mechanism linking neuroinflammation, impaired mitochondrial function, and ASD. FINANCIAL SUPPORT: Supported by the POWER Och!Doc Program and NSC grant 2016/23/D/NZ4/03572.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXXXI

Twórcy

autor

Zawadzka A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Cieslik M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Gewartowska M.

• Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Frontczak-Baniewicz M.

• Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland