Glial reaction in the spinal cord of the degenerating muscle mouse (Scn8a (dmu)).

The glial reaction was investigated in the spinal cord of the degenerating muscle (dmu) mouse, which harbours a null mutation in the voltage-gated sodium channel gene Scn8a and does not produce functional Nav1.6 channel. Glial fibrillary acidic protein (GFAP)- and Iba1-immunoreactivity were detected in numerous cells throughout the spinal cord of wild type mice. These cells had small cell bodies and ramified processes. The dmu mutation increased the number of GFAP-immunoreactive (-IR) cells and the length of their processes in the ventral horn but not in the dorsal horn of the lumbar spinal cord. The number of Iba1-IR cells was similar in cervical and lumbar spinal cords of wild type and dmu mice. However, Iba1-IR processes and their branches became thinner and showed a fine varinose appearance in dmu mice. The length of Iba1-IR processes was significantly reduced in dorsal and ventral horns of dmu mice. Double immunofluorescence also demonstrated the relationship between glial cells and motor neurons containing calcitonin gene-related peptide (CGRP), a marker for their degeneration. The dmu mutation caused increase in the length of GFAP-IR processes surrounding CGRP-IR motor neurons in the ventral horn. However, the thickness and length of Iba1-IR processes around CGRP-IR motor neurons were reduced by the mutation. The present study suggests that the dmu mutation causes astrocytic activation and microglial inactivation in the spinal cord. These changes may be associated with degeneration and activity of motor and sensory neuron in dmu mice.