Int J Med Sci 2020; 17(4):480-489. doi:10.7150/ijms.39101

Research Paper

Identification of VGF nerve growth factor inducible-producing cells in human spinal cords and expression change in patients with amyotrophic lateral sclerosis

Yasuhiro Noda1, Miruto Tanaka1, Shinsuke Nakamura1, Junko Ito2, Akiyoshi Kakita2, Hideaki Hara1, Masamitsu Shimazawa1✉

1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
2. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

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Citation:
Noda Y, Tanaka M, Nakamura S, Ito J, Kakita A, Hara H, Shimazawa M. Identification of VGF nerve growth factor inducible-producing cells in human spinal cords and expression change in patients with amyotrophic lateral sclerosis. Int J Med Sci 2020; 17(4):480-489. doi:10.7150/ijms.39101. Available from http://www.medsci.org/v17p0480.htm

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Abstract

Amyotrophic lateral sclerosis (ALS) is a serious disease characterized by the degeneration of motor neurons resulting in muscle weakness and paralysis. The neuroendocrine polypeptide VGF is localized in the central nervous system and peripheral endocrine neurons and is cleaved into several polypeptides with multiple functions. Previous studies revealed that VGF was decreased in the cerebrospinal fluid of ALS model mice and sporadic ALS patients. However, it is unknown which cells supply VGF in the spinal cord and a detailed localization is lacking. In this study, we evaluated the VGF-producing cells and protein localization using in situ hybridization and immunostaining in the spinal cords of ALS and control patients. VGF mRNA was localized both in the dorsal and anterior horns of the spinal cords. Moreover, in the anterior horn, VGF mRNA co-localized with a neurofilament heavy chain, which is a motor neuron marker, and VGF mRNA-positive motor neurons were decreased in the spinal cords of ALS patients. We revealed that VGF protein level was decreased in the anterior horn of ALS patients; however, the expression level of VGF protein was not changed in the posterior horn or white matter. Furthermore, the expression level of VGF protein was conserved in ALS patients with long-term survival. These results reveal that VGF is mainly supplied by human motor neurons, and suggest that VGF expression changes may be involved in ALS pathology.

Keywords: amyotrophic lateral sclerosis, VGF nerve growth factor inducible, motor neuron