Adenoviral interneuronal transportation after retrograde gene transfer in mice

Abstract

Although retrograde gene transfer from infected muscles to neurons by viral vectors has been known for years, it is still unknown whether interneuronal gene transportation of viral vectors occurs after retrograde gene transfer. To determine this, we injected adenoviral vectors carrying eGFP gene with or without a neural tracer into the right gastrocnemius muscles of mice. After 7 days, some spinal motor neurons were detected with green fluorescence but without the signal of neural tracer. In addition, nerves with green fluorescence could be noted in the right lumbosacral paraspinal muscles of viral-injected mice. The green fluorescence in the right lumbosacral paraspinal muscles might have resulted from retrograde gene transportation from the viral-injected gastrocnemius muscles to the spinal neurons, followed by interneuronal transfer and anterograde expression of eGFP in the axons belonging to neurons innervating the paraspinal muscles. This phenomenon of interneuronal transportation raises the possibility that we could treat motoneuron diseases by injection of viral vectors containing therapeutic genes into a few muscles resulting in widespread beneficial effects.