Extended Data Fig. 4: Related to Fig. 2: additional histological characterization of untreated and 4-HMA-treated brains from Hpdl^−/− mice.

a, Representative calbindin staining of cerebellar sections from P56-57 Hpdl^+/+, Hpdl^+/−, and 4-HMA-treated Hpdl^−/− mice and quantitation of dendrite height. The dendrite height is similar in all three groups of animals. b, Representative electron micrographs of the cortex in P11 Hpdl^+/+, Hpdl^+/−, and Hpdl^−/− pups, as well as Hpdl^−/− pups treated with 4-HMA. We observed minimal changes in cortical mitochondrial ultrastructure in Hpdl^−/− pups (panels C and G) compared to Hpdl^+/+ pups (panels A and E) and Hpdl^+/− pups (panels B and F). c, P11 Hpdl^−/− pups exhibit subtle loss of normal cortical layers of the cerebral cortex (panels C, G, K), as well as edema, shrinking of the cortical neurons, and red neurons. These histological findings are partially restored by supplementation with 4-HMA (panels D, H, L). d, P11 Hpdl^−/− pups do not exhibit major changes in hippocampal histology in comparison to Hpdl^+/+ pups, Hpdl^+/− pups, and Hpdl^−/− pups treated with 4-HMA. n = 4 for all groups. For panel a, significance was tested by two-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test.

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