Choi et al. (2017). Scientific Reports. doi: 10.1038/srep44989
…were perfused, and the brains were harvested and post-fixed as described34,84. Brain sections (40 μm) were labeled with either mouse or rabbit antibodies against tyrosine hydroxylase (TH, 1:5,000, Pel-Freez Biologicals, Rogers, AR) in PBS con- taining 0.1% Triton X-100, 5% BSA, and 5% goat serum. Sections were washed and incubated with Alexa Fluor 488 or 568 goat anti-mouse or anti-rabbit IgG respectively (1:200;…
Abstract
Abstract Reduction of mitochondrial complex I activity is one of the major hypotheses for dopaminergic neuron death in Parkinson’s disease. However, reduction of complex I activity in all cells or selectively in dopaminergic neurons via conditional deletion of the Ndufs4 gene, a subunit of the mitochondrial complex I, does not cause dopaminergic neuron death or motor impairment. Here, we investigated the effect of reduced complex I activity on non-motor symptoms associated with Parkinson’s disease using conditional knockout (cKO) mice in which Ndufs4 was selectively deleted in dopaminergic neurons ( Ndufs4 cKO). This conditional deletion of Ndufs4, which reduces complex I activity in dopamine neurons, did not cause a significant loss of dopaminergic neurons in substantia nigra pars compacta (SNpc), and there was no loss of dopaminergic neurites in striatum or amygdala. However, Ndufs4 cKO mice had a reduced amount of dopamine in the brain compared to control mice. Furthermore, even though motor behavior were not affected, Ndufs4 cKO mice showed non-motor symptoms experienced by many Parkinson’s disease patients including impaired cognitive function and increased anxiety-like behavior. These data suggest that mitochondrial complex I dysfunction in dopaminergic neurons promotes non-motor symptoms of Parkinson’s disease and reduces dopamine content in the absence of dopamine neuron loss.