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Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice

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Neural Regeneration Research 2021年第7期16卷 1258-1265页

作者： Ayaka Sugeno Wenhui Piao Miki Yamazaki Kiyofumi Takahashi Koji Arikawa Hiroko Matsunaga Masahito Hosokawa Daisuke Tominaga Yoshio Goshima Haruko Takeyama Toshio Ohshima Laboratory for Molecular Brain Science Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Biomolecular Engineering Laboratory Department of Life Science and Medical BioscienceGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Computational Bio Big-Data Open Innovation Laboratory(CBBD-OIL) National Institute of Advanced Industrial Science and Technology(AIST)TokyoJapan Research Organization for Nano and Life Innovation Waseda UniversityTokyoJapan Institute for Advanced Research of Biosystem Dynamics Waseda Research Institute for Science and EngineeringGraduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology(AIST)TsukubaJapan Department of Molecular Pharmacology and Neurobiology Graduate School of MedicineYokohama City UniversityYokohamaJapan

Recent studies have shown that mutation at Ser522 causes inhibition of collapsin response mediator protein 2(CRMP2) phosphorylation and induces axon elongation and partial recovery of the lost sensorimotor function after spinal cord injury(SCI).We aimed to reveal the intracellular mechanism in axotomized neurons in the CRMP2 knock-in(CRMP2KI) mouse model by performing transcriptome analysis in mouse sensorimotor cortex using micro-dissection punching system.Prior to that, we analyzed the structural pathophysiology in axotomized or neighboring neurons after SCI and found that somatic atrophy and dendritic spine reduction in sensorimotor cortex were suppressed in CRMP2KI mice.Further analysis of the transcriptome has aided in the identification of four hemoglobin genes Hba-a1, Hba-a2, Hbb-bs, and Hbb-bt that are significantly upregulated in wild-type mice with concomitant upregulation of genes involved in the oxidative phosphorylation and ribosomal pathways after SCI.However, we observed substantial upregulation in channel activity genes and downregulation of genes regulating vesicles, synaptic function, glial cell differentiation in CRMP2KI mice.Moreover, the transcriptome profile of CRMP2KI mice has been discussed wherein energy metabolism and neuronal pathways were found to be differentially regulated.Our results showed that CRMP2KI mice displayed improved SCI pathophysiology not only via microtubule stabilization in neurons, but also possibly via the whole metabolic system in the central nervous system, response changes in glial cells, and synapses.Taken together, we reveal new insights on SCI pathophysiology and the regenerative mechanism of central nervous system by the inhibition of CRMP2 phosphorylation at Ser522.All these experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee at Waseda University, Japan(2017-A027 approved on March 21, 2017;2018-A003 approved on March 25, 2018;2019-A026 approved on March 25, 2019).

关键词： CNS regeneration cortex CRMP2 hemoglobin metabolic pathway spinal cord injury spine transcriptome

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Oncofertility in Gynecologic Malignant Tumors

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Journal of Cancer Therapy 2015年第14期6卷 1176-1191页

作者： Masataka Adachi Kouji Banno Iori Kisu Megumi Yanokura Moito Iijima Takashi Takeda Kiyoko Umene Yuya Nogami Eiichiro tominaga daisuke Aoki Department of Obstetrics and Gynecology Keio University School of Medicine Tokyo Japan

Long-term survival is the priority in treatment of patients with malignant tumors. In the field of gynecology, fertility preservation has also recently become an important objective due to improved treatment outcomes and different needs of patients. Methods for fertility preservation include cervical conization, ovarian protection against radiation or chemotherapy for ovarian cancer since the ovary is hypersensitive to cancer therapies, treatment of gynecological cancer during pregnancy, and cryopreservation of oocytes, embryos or ovarian tissue before treatment of malignant tumors. Radical trachelectomy for early cervical cancer and treatment with medroxy progesterone acetate for early endometrial carcinoma are also options for fertility preservation, but the efficacy and risk of recurrence have yet to be fully evaluated. The first childbirth following uterine transplantation was also achieved last year and this success has expanded the potential for pregnancy and delivery among cancer survivors.

关键词： Gynecological Cancer Fertility Preservation Cryopreservation Uterine Transplantation Pregnancy

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