Fig. 1: Observations in Gclm-KO mice. | Molecular Psychiatry

Fig. 1: Observations in Gclm-KO mice.

From: Mitochondrial, exosomal miR137-COX6A2 and gamma synchrony as biomarkers of parvalbumin interneurons, psychopathology, and neurocognition in schizophrenia

Fig. 1

A Redox dysregulation affects mitochondrial morphology and reduces the expression of mitophagy markers in ACC. (a) 8-oxo-dG labeling of mitochondrial DNA in the ACC. Scale bar 20 μm. (b) Electron micrographs show mitochondrial morphology and mitophagosomes (red arrowheads) in Gclm-KO and Gclm-WT mice. Scale bar 200 nm. (c) Time course of pharmacological challenge with GBR (5 mg/kg, s.c. inj.) followed by MitoQ treatment (500 µmol/L, drinking water). (d, e) Mitophagy markers (Nix, Fundc1, and LC3B) labeling in ACC across four different groups. Scale bar 50μm. p < 0.05*, see representative micrograph in SI (Fig. S1A). B Expression of miR-137 and PV in ACC neurons. (a) Representative micrographs of miR-137 labeling in ACC across four different groups. Scale bar 50μm. (b) Micrographs showing double labeling for PV (green) and miR-137 (red) in ACC in Gclm-KO + GBR and Gclm-WT + PBS mice at P40. Scale bar 50 μm. (c) Representative micrographs of PV labeling in ACC across the four different groups. Scale bar 50μm. (d) The increased plasmatic levels of miR-137 in mice Gclm KO ± GBR) were rescued by mitoQ treatment (Gclm KO + GBR + MitoQ) back to baseline level, as observed in control animals (Gclm WT + PBS). (e) Positive correlation between miR-137 plasma and brain levels in Gclm KO + GBR (center panel), reversed by mitoQ treatment (Gclm KO + GBR + MitoQ; right panel). p < 0.01**, p < 0.05*. C Expression of COX6A2 in PV neurons in the ACC. (a) Colocalization labeling for COX6A2 (red) and PV (green) in ACC was increased in Gclm KO + GBR after mitoQ treatment. Scale bar 50 μm. (b) Decreased COX6A2 labeling intensity and COX6A2 / PV colocalization in ACC of P40 mice with or without GBR. (c, d) Local injection of miR-137 inhibitor (i-mmu-miR-137; miRCURY inhibitor Qiagen) in one hemisphere and scramble miR in the contralateral side; immunolabeling for COX6A2 (purple), PV (green), 8-oxo-dG (red), and Dapi (blue) in ACC of Gclm KO + GBR mice (c). Inhibition of miR-137 led to decreased oxidative stress marker 8-oxo-DG and increased PVI and COX6A2 staining in Gclm-KO + GBR as compared to sham injection (d). p < 0.001***, p < 0.01**, p < 0.05*.

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