IGF-I gene transfer by electroporation promotes regeneration in a muscle injury model.

The goal of this study was to determine whether insulin-like growth factor-I (IGF-I) gene delivery by electroporation promotes repair after muscle injury. An injury-repair model was created using mice in which a hamstring muscle was cut and sutured. A total of 50 microg of IGF-I DNA or green fluorescent protein (GFP) DNA (both in pCAGGS) was injected into the lesion and introduced into muscle cells by electrostimulation using an electric pulse generator. The number of regenerating muscle fibers in the IGF-I DNA group was significantly more than that in the GFP DNA group at 2 weeks after injection. The diameter of regenerating muscle fibers from the IGF-I DNA group was larger than that of the GFP DNA group at 4 weeks after injection. There was no significant difference in the serum IGF-I concentration between the IGF-I DNA group and the GFP DNA group at 1, 2, and 4 weeks after injection. However, muscle IGF-I concentration in the IGF-I DNA injection group was significantly greater than that in the GFP DNA injection group at 2 weeks after injection. These results demonstrated that the effects of enhanced IGF-I production were local and limited to the injected area. The ratio (injected/uninjected; intact) of the amplitude of compound muscle action potentials (CMAP) in the IGF-I DNA injection group was greater than that in the GFP DNA injection group at 4 weeks after injection and of the control group. In conclusion, IGF-I gene transfer by electroporation proved to be a simple, safe, inexpensive, and effective method to promote the regeneration of injured muscles in our injury model.

Reduced hippocampal LTP in mice lacking a presynaptic protein: complexin II.

The SNAP receptor (SNARE) complex is a core complex specialized for synaptic vesicle exocytosis, and the binding of SNAPs to the complex is an essential step for neurotransmitter release. Complexin I and II have been identified as SNARE-complex-associated proteins. Importantly, complexins compete with alpha-SNAP for binding to the complex, suggesting that complexins may modulate neurotransmitter release process. To examine this possibility and to understand the physiological function of complexins, we generated complexin II knockout mice. The complexin-II-deficient mice (-/-) were viable and fertile, and appeared normal. Electrophysiological recordings in the mutant hippocampus showed that ordinary synaptic transmission and paired-pulse facilitation, a form of short-term synaptic plasticity, were normal. However, long-term potentiation (LTP) in both CA1 and CA3 regions was impaired, suggesting that complexin II may not be essential for synaptic vesicle exocytosis, but it does have a role in the establishment of hippocampal LTP.