Expression of secreted phosphoprotein 1 (osteopontin) in human sensorimotor cortex and spinal cord: Changes in patients with amyotrophic lateral sclerosis

Secreted phosphoprotein 1 (SPP1, also known as osteopontin) is expressed in large pyramidal neurons in the primary motor cortex (M1) of certain primate species, including macaque monkeys, but not of rodents. Based on this, we suggested that SPP1 expression may reflect the functional or structural specialization of highly developed corticospinal systems. In the present study, we further characterized SPP1 in the human central nervous system by investigating its expression in the primary somatosensory cortex (S1) and spinal cord, in addition to M1. Although a small number of SPP1-positive pyramidal neurons were observed in S1, the number was smaller than that in M1. In the cervical segment of the spinal cord, SPP1 was principally expressed in choline acetyltransferase-positive motor neurons in lamina IX. We also examined SPP1 expression in patients with amyotrophic lateral sclerosis (ALS), a disease characterized by the degeneration of motor neurons. When SPP1 expression was compared in neurons of the same size range, expression in both M1 and the spinal cord of ALS patients was lower than that of subjects without ALS. SPP1 expression was especially reduced in surviving large neurons in both M1 and the spinal cord of ALS patients. The results further support the concept that SPP1 has a role in the specialization of motor projection neurons and suggest that its reduced expression may be implicated in the neurodegeneration seen in ALS.