Effect on motor neuron survival in mutant SOD1 (G93A) transgenic mice by Bcl-2 expression using retrograde axonal transport of adenoviral vectors

Abstract

We investigated the effect of exogenous Bcl-2 on motor neurons in transgenic mice expressing human Cu/Zn superoxide dismutase with a G93A mutation (G93A mice), using adenoviral vectors with a cassette for Bcl-2 (AxCALNLBcl-2) and Cre recombinase (AxCANCre) to express Bcl-2 by Cre-loxP recombination. We were able to detect Bcl-2 in the hypoglossal nuclei of G93A mice for at least 8 weeks after inoculation with AxCALNLBcl-2 followed by inoculation with AxCANCre into the tongue of 10-week-old G93A mice. We examined the morphological changes of motor neurons in the hypoglossal nuclei of each mouse at 25 weeks of age, at which time the G93A mice manifested signs of neural degeneration. We found that the number of motor neurons was significantly higher in the G93A mice with both vectors than in those with AxCALNLBcl-2 alone or without inoculation. Further, we observed an obvious reduction of vacuole formations and reactive astrocytes in and around the hypoglossal nuclei of G93A mice with both vectors. These results suggest that expression of Bcl-2 introduced by our system has a protective effect on degeneration of motor neurons in G93A mice.