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Yuji Takihara, Masaru Inatani, Toshihiro Inoue, Keiichiro Iwao, Yoshihiro Takamura, Hidenobu Tanihara; Age-related changes in mitochondrial axonal transport in the mammalian CNS in vivo. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2408.
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Mitochondria play essential roles in the function and survival of neurons by generating ATP, maintaining Ca2+ homeostasis, and signaling in apoptosis. Because neurons have a highly polarized structure, particularly axons, mitochondria must be transported and properly distributed to function. To study mitochondrial transport under physiological conditions, in vivo imaging of mitochondrial transport has been developed in the Drosophila nervous system, the mouse peripheral nervous system, and the zebrafish nervous system. However, in vivo imaging of mitochondrial axonal transport in the mammalian central nervous system (CNS) has not been achieved. This has limited our understanding of mitochondrial axonal transport in the CNS of aged mammals. The purpose of the present study is to characterize age-related changes in mitochondrial axonal transport of retinal ganglion cells (RGCs) in mice aged up to 23-25 months in vivo.
In vivo imaging using two-photon microscopy of mouse RGCs was conducted under general anesthesia. We quantified and compared mitochondrial axonal transport in mice at 2 (young), 4 (adult), 12-13 (middle-aged) and 23-25 (old) months of age.
In vivo imaging of RGCs showed active mitochondrial axonal transport with preserved blood flow. The number of mitochondria transported in axons did not decrease in the middle-aged and old mice, compared to that in the adult mice. In contrast, the duration (adult: 36.5 ± 1.4 s; middle-aged: 25.6 ± 0.9 s; old: 22.7 ± 1.1 s, P < 0.0001) of transport decreased with age. Consistent with this result, the duty cycle decreased with age. However, in vivo imaging of RGCs showed the consistent appearance of four transport patterns among the young, adult, middle-aged, and old mice. Almost all mitochondria were transported unidirectionally. Furthermore, the ratios of anterograde/retrograde transport were consistent through the four age groups.
In vivo imaging of mouse RGCs shows that mitochondrial axonal transport is highly dynamic under physiological conditions. In vivo imaging of RGCs reveals that the duration of mitochondrial axonal transport and the duty cycle decrease with age in the mammalian CNS. However, totally organized mitochondrial axonal transport patterns are preserved in old mice aged up to 23-25 months. These age-related changes of mitochondrial axonal transport may contribute to age-related increase in glaucoma incidence.
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