Administration of prosaposin-derived neurotrophic factor to neural tube defects facilitates regeneration and restores neurological functions
Sakirul Khan,
Akihide Takeuchi,
Hiroaki Nabeka,
Farzana Khan,
Tetsuya Shimokawa,
Sota Takanezawa,
Takashi Saitou,
Takeshi Imamura,
Tetsuya Tachibana,
Akira Nishizono,
Fumihiko Hamada,
Seiji Matsuda
Affiliations
Sakirul Khan
Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; Department of Microbiology, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan; Corresponding author
Akihide Takeuchi
Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Hiroaki Nabeka
Department of Physiological Chemistry, College of Pharmaceutical Sciences, School of Clinical Pharmacy, Matsuyama University, Matsuyama, Ehime 790-8578, Japan
Farzana Khan
Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; Department of Human Anatomy, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan
Tetsuya Shimokawa
Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Sota Takanezawa
Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Takashi Saitou
Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Takeshi Imamura
Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan
Tetsuya Tachibana
Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Matsuyama, Ehime 790-8566, Japan
Akira Nishizono
Department of Microbiology, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan; Research Center for Global and Local Infectious Diseases, Oita University, Yufu, Oita 879-5593, Japan
Fumihiko Hamada
Department of Human Anatomy, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan
Seiji Matsuda
Department of Developmental Biology and Functional Genomics, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; Corresponding author
Summary: Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We attempted to elucidate the pathogenesis of NTDs and propose a therapeutic strategy. Intra-amniotic treatment with prosaposin-derived 18-mer peptide (PS18) protected the spinal cord from secondary damage and rescued neurological function in an established chicken model of spina bifida aperta (SBA), the severe type of NTDs. PS18 promoted the formation of a neuroectodermal covering over the defective neural tube within 24-h after treatment, enhanced the regeneration/restoration process, and decreased apoptotic activity in the developing spinal cord. PS18 reduced the SBA wound and almost completely formed the spinal cord. SBA chicks that received PS18 exhibited relatively normal walking and sensorimotor responses, and reduced pain-associated behavior in postnatal life. In conclusion, PS18 is a promising therapeutic agent for NTDs and may be useful for treating other types of spinal cord injuries.
