MILON mice were viable and developed normally, but after about two months the level of Tfam in the neocortex declined. In-situ hybridizations showed that mitochondrial RNA levels had also decreased markedly by that age and continued to decline to about 50 percent of normal by six months. A similar decrease occurred in the activity of respiratory chain components encoded by the mitochondrial genome, including cytochrome c oxidase and NADH-dehydrogenase.

Morphologically, the neocortex showed nerve cell loss, axonal degeneration, inflammation, and astrocyte activation, the researchers report in today's Journal of Neuroscience. However, these changes only occurred in mice five months or older, indicating a time lag between respiratory chain deficiency and neurodegeneration.

"This is a very interesting paper that clearly shows that mitochondrial dysfunction can cause late-onset brain degeneration, but the pathology is different from what is seen in Alzheimer's or Parkinson's. In [MILON mice] there is a vacuolar degeneration that may be due to the rapidity and severity of the mitochondrial defect," said Flint Beal, chair of the neurology/neuroscience department at Cornell University Medical College.-Tom Fagan.

Reference:Sorensen L, Ekstrand M, Silva JP, Lindqvist E, Xu B, Rustin P, Olson L, Larsson NG. Late-onset corticohippocampal neurodepletion attributable to catastrophic failure of oxidative phosphorylation in MILON mice. J Neuroscience October 15;(21):8082-8090. Abstract