Methylmercury poisoning of the developing nervous system: morphological changes in neuronal mitochondria

Neonatal rats received s.c. injections of methylmercuric chloride (MeHg) in physiological saline (1.5 mg Hg/kg b.wt.) at 48-h intervals from postnatal day 2 to day 50. Littermate controls were injected with an equivalent volume of saline. All animals were perfused on day 51 and blocks of cerebral cortex were prepared for electron microscopy. Ultrastructural changes in mitochondria were evident in the dendrites, axons and presynaptic terminals of cortical neurones in the MeHg-treated animals. Many mitochondria were condensed with an increased electron density of the inner matrix. Some profiles exhibited regressive alterations, including a disruption of cristae and the inner membrane with an accumulation of electron-opaque material in the matrix. Membranous whorls were found in association with the most degenerate mitochondria. A morphometric analysis of mitochondrial profiles in the neuropil of layer I revealed a 24% decrease in average profile area and a 16% increase in the number of profiles per micrograph in the MeHg-treated animals. These pathological changes in mitochondrial ultrastructure are consistent with an inhibition of mitochondrial respiration. The observed increase in the number of mitochondrial profiles may reflect a compensation by cortical neurons for the reduced efficiency of aerobic metabolism in the individual organelle.