Protein kinase C gamma (PKCγ) as a novel marker to assess the functional status of the corticospinal tract in experimental autoimmune encephalomyelitis (EAE).

In the spinal cord, PKCγ is an important kinase found in a specific subset of excitatory interneurons in the superficial dorsal horn and in axons of the corticospinal tract (CST). The major interest in spinal PKCγ has been its influences on regulating pain sensitivity but its presence in the CST also indicates that it has a significant role in locomotor function. A hallmark feature of the animal model commonly used to study Multiple Sclerosis, experimental autoimmune encephalolomyelitis (EAE) are motor impairments associated with the disease. More recently, it has also become recognized that EAE is associated with significant changes in pain sensitivity. Given its role in generating pain hypersensitivity and its presence in a major tract controlling motor activity, we set out to characterize whether EAE was associated with changes PKCγ levels in the spinal cord. We show here that EAE triggers a significant reduction in the levels of PKCγ, primarily in the CST. We did not observe any significant changes in PKCγ levels in the superficial dorsal horn but in general the levels tended to be below control levels in this region. In a final experiment we assessed the levels of PKCγ in the spinal cord of EAE mice that had recovered gross locomotor function and compared this to the levels found in EAE mice with chronic deficits. Our findings demonstrate that PKCγ levels are dynamic and that in later stages of the disease, its expression is dependent on the degree of motor function in the model. Taken together these results suggest that PKCγ may be a useful marker in the disease to monitor the status of the CST.