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Editors Selection IGR 14-4

Animal Models: Neuroprotection

Comment by Masaru Inatani on:

51837 Failure of axonal transport induces a spatially coincident increase in astrocyte BDNF prior to synapse loss in a central target, Crish SD; Dapper JD; MacNamee SE et al., Neuroscience, 2013; 229: 55-70

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The loss of anterograde transport in the axon is a common feature of neurodegenerative diseases. Crish et al. demonstrated that the structure of axon terminals of the retinal ganglion cells (RGC) in the superior colliculus (SC) was maintained long after the disappearance of axonal transport in mouse glaucoma. To examine anterograde transport in RGC, the authors used intravitreal injections of cholera toxin β conjugated to Alexa Fluor 488 and tried to identify positively-labeled regions in the SC. They found that the complete depletion of anterograde labeling in the SC of a ten-month-old DBA/2J mouse, a glaucoma mouse model, was accompanied by an intense localization of brain-derived neurotrophic factor (BDNF) in the SC. Immunohistochemistry demonstrated that BDNF was mostly localized in the activated astrocytes in the SC. In contrast, quantitative PCR demonstrated a reduced expression of Bdnf mRNA. In general, the expression of mRNAs encoding synaptic structure-related molecules remained unchanged, whereas the expression of genes for axonal transport-related molecules was diminished. Therefore, it was inferred that the increased levels of BDNF were not due to either de novo synthesis in the activated astrocytes or the supply through anterograde transport in the optic nerve. The authors suggested that activated astrocytes uptake the extracellular BDNF released from neuronal cells in the SC. Their data coincided to the events in the neurodegenerative disorders in which BDNF increase and astrocyte hypertrophy attenuate the destruction of synapse structures after disturbance of axonal transport. These findings suggested that the normal function can be restored even after the depletion of the axonal transport in the optic nerve. Furthermore, exogenous BDNF application to the SC may be a valuable therapeutic strategy to maintain the RGC axonal structures.

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