Connexin 30 deficiency ameliorates the disease progression of amyotrophic lateral sclerosis model mice by suppressing glial inflammation.

Connexin (Cx)30, which forms gap junction interconnecting astrocytes, regulates cell adhesion and migration and modulates glutamate transport. The expression levels of Cx30 are known to be upregulated on the activated astroglia at CNS inflammation lesion, including mutant-SOD1 transgenic ALS model mice spinal cord lesion. We aimed to clarify the role of Cx30 in mSOD1-transgenic mice. Cx30 was highly expressed in the pre-clinical stage of mSOD1-Tg mice. Cx30-knockout mSOD1 mice showed a delayed onset and tended to extend the survival period (log-rank, p = 0.09). At the progressive and end stages, anterior horn cells were more preserved in Cx30-knockout mSOD1 mice. Additionally, dorsal horn cells were kept more in Cx30-knockout mSOD1 mice at all stages. In the lesion of Cx30-knockout mSOD1 mice, GFAP and C3 positive inflammatory astroglia were decreased. Further, in Cx30-knockout mSOD1 mice, the amount of NOS2 protein at the end stage and the amount of Cx43 protein at the pre-clinical stage were smaller than in mSOD1 mice. These findings indicated reduced expression of astroglial Cx30 in the early stage of ALS model mice protects neurons by the attenuation of glial inflammation. Gene expression in the mice spinal cord was mesured at the 8 weeks-old wild type mice, mutant SOD1 transgenic mice and connexin30-deficient mutant SOD1 transgenic mice.