| December 14, 2011 |
A Mouse Helps Explain Why Some People Don't Want to Eat
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Eating disorders such as anorexia are some of the most perplexing psychiatric disorders – difficult to characterize and difficult to treat. By studying a mouse with an eating disorder, a Swedish-led medical team headed by Jeanette Johansen, Ph.D., Ida Nilsson, Ph.D., and Charlotte Lindfors, and in cooperation with Jackson Laboratory professors Leah Rae Donahue, Ph.D., Muriel Davisson, Ph.D., and Derry Roopenian, Ph.D., recently reported that a defective mitochondrial oxidative phosphorylation pathway may be partially to blame (Lindfors et al. 2011). The team's findings may lead to therapies for some human eating disorders.
The anx/anx mouse
The abnormal feeding behaviors of the anorexia mouse model B6C3Fe a/a-anx/J (anx/anx, 000624) are similar to those of children who exhibit one or more of the following: failure to thrive, anorexia nervosa, or cachexia (wasting). The mouse has a poor appetite, and dies at a very young age (about three weeks old), likely from severe starvation. It has several neurological abnormalities, including body tremors, head weaving, hyperactivity, and an uncoordinated gait. Several hypothalamic systems that regulate appetite and energy metabolism are dysfunctional. Notably, two main populations of appetite-regulating neurons in the arcuate nucleus (Arc) of the hypothalamus degenerate. The anx/anx mouse also exhibits many of the symptoms associated with mitochondrial oxidative phosphorylation system (OXPHOS) complex I (CI) deficiencies, including poor feeding, neurodegeneration, and muscle weakness. Because poor feeding behavior and neurodegeneration are also common in people with a dysfunctional OXPHOS, the researchers hypothesized that the defects of the anx/anx mouse are related to OXPHOS and CI deficiencies.
Anx/anx mice exhibit a mitochondrial metabolism defect
As expected, the Swedish-led team found that the hypothalamus of the anx/anx mouse has abnormally low levels of assembled OXPHOS CI and a 29% reduction in CI-specific respiration efficiency. They also found an increase in reactive oxygen species (ROS) production and evidence of oxidative stress. Furthermore, they mapped one of the CI assembly factor genes, NADH dehydrogenase (ubiquinone) 1α-subcomplex, assembly factor 1 (Ndufaf1), to the anx locus and found that its expression is down-regulated in the anx/anx mouse. These results suggested that the eating disorders and hypothalamic neurodegeneration in the anx/anx mouse are attributable to a dysfunctional mitochondrial CI and may lead to therapies for anorexia and related diseases.
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