Editors' ChoiceNeurodegeneration

Neurons cool off

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Science Translational Medicine  25 Feb 2015:
Vol. 7, Issue 276, pp. 276ec33
DOI: 10.1126/scitranslmed.aaa8330

It’s common wisdom that a cold shower is good for your health. Now, Peretti et al. show that Rbm3, a protein induced by cold shock, triggers neurons to form new synapses.

Low body temperature in hibernating mammals leads to a reversible loss of synaptic contacts that are efficiently re-established upon rewarming. Using electron microscopy, Peretti et al. report that the induction of a hibernation-like body temperature in mice for as little as 45 minutes caused a similar loss of synaptic connections that were regained upon rewarming the animals. This capacity for synaptic regeneration after cold trauma was lost in mice suffering from two neurodegenerative diseases. The impaired cooling-induced regeneration of synapses in mice suffering from either prion-like disease or Alzheimer’s disease was associated with a decrease in one of the known cold-shock proteins, the RNA-binding motif protein RBM3. The authors show that RNAi-based knockdown of RBM3 exacerbated the loss of synapses in both disease models and accelerated disease progression. Conversely, the enhanced ectopic expression of RBM3 using lentiviral-based delivery to the hippocampus, the brain region that is important for memory formation, restored cold-induced synaptic regeneration in the two mouse models of neurodegenerative disease. Moreover, RBM3 overexpression reduced prion neuropathology, prevented neuronal loss, and significantly enhanced the survival of prion-diseased animals. Ectopic RBM3 expression before exposure of young mice with neurodegenerative disease to two consecutive cold-shocks one week apart was sufficient to boost endogenous RBM3 expression in the brain and to achieve synaptic protection.

Although the RBM3-based mechanism of synaptic regeneration remains unknown, these data suggest that RBM3 might have long-term neuroprotective effects. The results of this study could have far-reaching consequences for enhancing cold-shock pathways as a new therapeutic approach for treating neurodegenerative disease.

D. Peretti et al., RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature 518, 236–239 (2015). [PubMed]

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