Article
Developmental Biology
Fumiyasu Imai, Mike Adam, S. Steven Potter, Yutaka Yoshida
Summary: The study reveals the crucial role of HoxD family transcription factors in the specificity of monosynaptic sensory-motor connections in the spinal cord. Mice lacking Hoxd9, Hoxd10 and Hoxd11 show locomotion defects and aberrant axon development in quadriceps motor neurons.
Article
Anatomy & Morphology
Yi-Syue Tsou, Chih-Yang Wang, Ming-Yuan Chang, Tsung- Hsu, Meng-Ting Wu, Yi-Hsin Wu, Wan-Ling Tsai, Jian-Ying Chuang, Tzu-Jen Kao
Summary: Proper guidance of neuronal axons to their targets is crucial for neural circuit assembly during nervous system development, with Vav2 playing an essential role in motor axon pathfinding through interaction with the Src pathway and Netrin-1 regulation. Vav2 expression in LMC neurons is critical for the directional growth of axons, highlighting the importance of Vav proteins in mediating axonal trajectories.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Neurosciences
Wan-Ling Tsai, Chih-Ju Chang, Chih-Yang Wang, Tsung- Hsu, Ming-Yuan Chang, Yi-Hsin Wu, Pei-Shan Chang, Kai-Lun Lin, Jian-Ying Chuang, Artur Kania, Tzu-Jen Kao
Summary: The study demonstrates the essential role of paxillin in motor axon guidance in both chick and mouse embryos. Paxillin is involved in the Ephrin-Eph signaling pathway, influencing the trajectory selection of LMC axons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Ryan W. Castro, Mikayla C. Lopes, Lindsay M. De Biase, Gregorio Valdez
Summary: Microglia display region-dependent deleterious features with age and diseases in the brain, and it remains unclear if similar phenotypic heterogeneity exists in the spinal cord. The study shows that regardless of regional location, spinal cord microglia become increasingly activated during aging. However, microglia in the ventral horn lose spatial organization and aggregate around motor neurons, potentially affecting motor neuron function.
Article
Clinical Neurology
Nicolas Delestree, Evangelia Semizoglou, John G. Pagiazitis, Aleksandra Vukojicic, Estelle Drobac, Vasilissa Paushkin, George Z. Mentis
Summary: Serotonin plays a crucial role in regulating neuronal networks responsible for various essential behaviors. Dysfunction of serotonergic neurotransmission is found in spinal muscular atrophy (SMA), a neurodegenerative disease. The study shows severe dysfunction of serotonergic neuromodulation in SMA mice, suggesting that targeting 5-HT neuromodulation could be a potential therapeutic approach.
Article
Neurosciences
Menghon Cheah, Yuyan Cheng, Veselina Petrova, Anda Cimpean, Pavla Jendelova, Vivek Swarup, Clifford J. Woolf, Daniel H. Geschwind, James W. Fawcett
Summary: Sensory dorsal root ganglion (DRG) neurons in the peripheral branch regenerate readily after injury, but not in the central branch. However, expression of a9 integrin and its activator kindlin-1 (a9k1) enables axons to interact with tenascin-C, promoting extensive regeneration and reconnection of sensory axons in the spinal cord. Transcriptomic analyses of adult male rat DRG neurons revealed that a9k1 expression upregulates a known peripheral nerve regeneration program. Coupling a9k1 treatment with dorsal root axotomy leads to extensive central axonal regeneration, accompanied by the expression of a distinctive CNS regeneration program involving genes associated with ubiquitination, autophagy, ER, trafficking, and signaling. Pharmacological inhibition of these processes blocks axon regeneration, validating their causal contributions to sensory regeneration.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biology
Sang Hwa Kim, Kye D. Nichols, Eric N. Anderson, Yining Liu, Nandini Ramesh, Weiyan Jia, Connor J. Kuerbis, Mark Scalf, Lloyd M. Smith, Udai Bhan Pandey, Randal S. Tibbetts, Jeannie Chin
Summary: Mutations in UBQLN2 cause X-linked forms of ALS and FTD, but the underlying mechanisms are unknown. Studying ALS-associated mutants of UBQLN2 in Drosophila, it was found that they trigger heat stress-dependent neurodegeneration. A genetic modifier screen identified endolysosomal and axon guidance genes, including the netrin receptor Unc-5, as key regulators of UBQLN2 toxicity. Reduced dosage of Unc-5 or its coreceptor Dcc/frazzled alleviated neurodegenerative phenotypes in flies expressing UBQLN2(ALS) alleles. Further experiments using iPSCs and iMNs demonstrated lysosomal defects and cytosolic UBQLN2 inclusions, neurite complexity reduction, and growth cone defects, which were partially reversed by silencing of UNC5B and DCC. These findings suggest altered growth cone dynamics as a conserved pathomechanism in UBQLN2-associated ALS/FTD.
Article
Biochemistry & Molecular Biology
Takafumi Fukui, Hironao Tateno, Takashi Nakamura, Yuma Yamada, Yusuke Sato, Norimasa Iwasaki, Hideyoshi Harashima, Ken Kadoya
Summary: This study investigated the potential of liposomes as an efficient drug-delivery system for treating disorders of the central nervous system. By optimizing the liposomes and conducting experiments in a rat model, the study confirmed successful retrograde transport to the spinal cord and dorsal root ganglia. Modifying the liposomes with different substances improved their transport efficiency, providing valuable insights for the future development of novel DDS targeting the CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Yuko Kawamoto, Mikiko Tada, Tetsuya Asano, Haruko Nakamura, Aoi Jitsuki-Takahashi, Hiroko Makihara, Shun Kubota, Shunta Hashiguchi, Misako Kunii, Toshio Ohshima, Yoshio Goshima, Hideyuki Takeuchi, Hiroshi Doi, Fumio Nakamura, Fumiaki Tanaka
Summary: This study found that pCRMP1 may be involved in the pathogenesis of axonopathy in ALS, leading to spheroid formation through the proximal progression of axonopathy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Tzu-Jen Kao, Chih-Yang Wang, Tsung-I. Hsu, Yi-Hsin Wu, Jiang-Ying Chuang, Chi-Chen Huang, Cheng-Ta Hsieh
Summary: The study reveals the essential role of TDP-43 in axon guidance of spinal motor neurons and its regulation of EphB expression in mediating LMC pathfinding. These findings contribute to a better understanding of the mechanisms underlying neural circuit formation.
NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Harun N. Noristani, Hyukmin Kim, Shuhuan Pang, Jian Zhong, Young-Jin Son
Summary: Targeting B-RAF and PTEN enhances the intrinsic growth potential of DC axons after SCI, offering a novel strategy for promoting robust long-distance regeneration of primary sensory axons.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biology
Saul Bello-Rojas, Martha W. Bagnall
Summary: The study found that sister V2a/b neurons in the zebrafish spinal cord receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets.
Article
Cell Biology
Guo-Ying Feng, Nai-Li Zhang, Xiao-Wei Liu, Ling-Xi Tong, Chun-Lei Zhang, Shuai Zhou, Lu-Ping Zhang, Fei Huang
Summary: Studies have shown that serum response factor is beneficial for axonal regeneration of peripheral nerves. However, its role after central nervous system injury remains unclear. In this study, we established a rat model of T9-T10 spinal cord transection injury and found that serum response factor expression in injured spinal cord gray matter neurons gradually increased with time, reaching its peak on the 7th day. Overexpression of serum response factor promoted motor function recovery, increased nerve fibers in the injured spinal cord, and restored axon and myelin sheath morphology. Silencing serum response factor had the opposite effects.
NEURAL REGENERATION RESEARCH
(2023)
Review
Endocrinology & Metabolism
Yimin Zou
Summary: Most spinal cord injury cases are anatomically incomplete, with potential for functional restoration through new axon growth and synaptic connections. Rehabilitation can partially restore function, but limitations and uncertainties still exist.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Pharmacology & Pharmacy
Qiong Zhang, Mingfu Liu, Haibin Nong, Yanan Zhang, Yiguang Bai, Pan Liu, Shaohui Zong, Gaofeng Zeng
Summary: TFHL has shown to improve motor function recovery and promote spinal cord tissue repair in rats with spinal cord injury (SCI). It reduces apoptosis and improves the functional status of neurons. TFHL also improves cell morphology, microstructure, and axonal regeneration of damaged spinal motor neurons, and promotes the secretion of neurotrophic factors. Furthermore, TFHL promotes autophagy and related protein expression both in vivo and in vitro.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Anatomy & Morphology
Fumiyasu Imai, Yutaka Yoshida
DEVELOPMENTAL DYNAMICS
(2018)
Article
Neurosciences
Zirong Gu, Masaki Ueno, Kelsey Klinefelter, Madhulika Mamidi, Takeshi Yagi, Yutaka Yoshida
JOURNAL OF NEUROSCIENCE
(2019)
Article
Developmental Biology
Fumiyasu Imai, Mike Adam, S. Steven Potter, Yutaka Yoshida
Summary: The study reveals the crucial role of HoxD family transcription factors in the specificity of monosynaptic sensory-motor connections in the spinal cord. Mice lacking Hoxd9, Hoxd10 and Hoxd11 show locomotion defects and aberrant axon development in quadriceps motor neurons.
Article
Neurosciences
Yuka Nakamura, Masaki Ueno, Jesse K. Niehaus, Richard A. Lang, Yi Zheng, Yutaka Yoshida
Summary: Deleting RhoA and RhoC genes to eliminate extrinsic inhibitory pathways, as well as deleting the PTEN gene to enhance intrinsic regenerative response, were found to promote neural circuit rewiring through a combinatorial approach. While this method increased the potential for rewiring, it did not significantly impact axon regrowth across the lesion and motor recovery.
JOURNAL OF NEUROSCIENCE
(2021)