Substance P immunoreactive cell reductions in cerebral cortex of Niemann-Pick disease type C mouse

Niemann-Pick disease type C (NPC) is characterized by progressive neurodegeneration and arises from mutations in the NPC1 gene. Cholesterol has received most attention in the pathogenesis of NPC, but normalizing lipid levels in humans or mouse does not prevent neurodegeneration. In NPC mouse, neuronal degeneration in the cerebellum is the most commonly detected change, and thus previous studies have tended to focus on the cerebellum, especially Purkinje cells. Although numerous peptides have been found in the mammalian central nervous system, little data on neurotransmitters in NPC are available, and information on neurotransmitter system abnormalities could explain the complex and characteristic deficits of NPC. Thus, we performed an immunohistochemical study on NPC mouse cortices to compare cell numbers exhibiting vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and substance P (SP) immunoreactivity. In terms of VIP and NPY-immunoreactive (ir) cell numbers in the cerebral cortex, SP-ir cells were significantly reduced by about 90% in NPC (-/-) versus NPC (+/+) mouse, and were also mildly decreased in frontal and parietal NPC (+/-) versus NPC (+/+) mouse cortex. This study demonstrates for the first time, reduced number of SP-ir cells in the NPC mouse cortex.