Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model
Spina bifida aperta (SBA), one of the most common congenital malformations, causes lifelong neurological complications, particularly in terms of motor dysfunction. Fetuses with SBA exhibit voluntary leg movements in utero and during early neonatal life, but these disappear within the first few weeks...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2017-12-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/10/12/1421 |
| _version_ | 1819261660210135040 |
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| author | Md. Sakirul Islam Khan Hiroaki Nabeka Farzana Islam Tetsuya Shimokawa Shouichiro Saito Xuan Li Soichiro Kawabe Fumihiko Hamada Tetsuya Tachibana Seiji Matsuda |
| author_facet | Md. Sakirul Islam Khan Hiroaki Nabeka Farzana Islam Tetsuya Shimokawa Shouichiro Saito Xuan Li Soichiro Kawabe Fumihiko Hamada Tetsuya Tachibana Seiji Matsuda |
| author_sort | Md. Sakirul Islam Khan |
| collection | DOAJ |
| description | Spina bifida aperta (SBA), one of the most common congenital malformations, causes lifelong neurological complications, particularly in terms of motor dysfunction. Fetuses with SBA exhibit voluntary leg movements in utero and during early neonatal life, but these disappear within the first few weeks after birth. However, the pathophysiological sequence underlying such motor dysfunction remains unclear. Additionally, because important insights have yet to be obtained from human cases, an appropriate animal model is essential. Here, we investigated the neuropathological mechanisms of progression of SBA-like motor dysfunctions in a neural tube surgery-induced chicken model of SBA at different pathogenesis points ranging from embryonic to posthatch ages. We found that chicks with SBA-like features lose voluntary leg movements and subsequently exhibit lower-limb paralysis within the first 2 weeks after hatching, coinciding with the synaptic change-induced disruption of spinal motor networks at the site of the SBA lesion in the lumbosacral region. Such synaptic changes reduced the ratio of inhibitory-to-excitatory inputs to motor neurons and were associated with a drastic loss of γ-aminobutyric acid (GABA)ergic inputs and upregulation of the cholinergic activities of motor neurons. Furthermore, most of the neurons in ventral horns, which appeared to be suffering from excitotoxicity during the early postnatal days, underwent apoptosis. However, the triggers of cellular abnormalization and neurodegenerative signaling were evident in the middle- to late-gestational stages, probably attributable to the amniotic fluid-induced in ovo milieu. In conclusion, we found that early neonatal loss of neurons in the ventral horn of exposed spinal cord affords novel insights into the pathophysiology of SBA-like leg dysfunction. |
| first_indexed | 2024-12-23T19:45:20Z |
| format | Article |
| id | doaj.art-ba42dc8c321f4ad3afa6d3f7c05f30b8 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-23T19:45:20Z |
| publishDate | 2017-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-ba42dc8c321f4ad3afa6d3f7c05f30b82022-12-21T17:33:33ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112017-12-0110121421143210.1242/dmm.031054031054Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken modelMd. Sakirul Islam Khan0Hiroaki Nabeka1Farzana Islam2Tetsuya Shimokawa3Shouichiro Saito4Xuan Li5Soichiro Kawabe6Fumihiko Hamada7Tetsuya Tachibana8Seiji Matsuda9 Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Laboratory of Veterinary Anatomy, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu 501-1128, Japan Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Fukui Prefectural Dinosaur Museum, Katsuyama, Fukui 911-8601, Japan Department of Human Anatomy, Faculty of Medicine, Oita University, Yufu, Oita 879-5593, Japan Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Matsuyama 790-8566, Japan Department of Anatomy and Embryology, Graduate School of Medicine, Ehime University, Toon 791-0295, Ehime, Japan Spina bifida aperta (SBA), one of the most common congenital malformations, causes lifelong neurological complications, particularly in terms of motor dysfunction. Fetuses with SBA exhibit voluntary leg movements in utero and during early neonatal life, but these disappear within the first few weeks after birth. However, the pathophysiological sequence underlying such motor dysfunction remains unclear. Additionally, because important insights have yet to be obtained from human cases, an appropriate animal model is essential. Here, we investigated the neuropathological mechanisms of progression of SBA-like motor dysfunctions in a neural tube surgery-induced chicken model of SBA at different pathogenesis points ranging from embryonic to posthatch ages. We found that chicks with SBA-like features lose voluntary leg movements and subsequently exhibit lower-limb paralysis within the first 2 weeks after hatching, coinciding with the synaptic change-induced disruption of spinal motor networks at the site of the SBA lesion in the lumbosacral region. Such synaptic changes reduced the ratio of inhibitory-to-excitatory inputs to motor neurons and were associated with a drastic loss of γ-aminobutyric acid (GABA)ergic inputs and upregulation of the cholinergic activities of motor neurons. Furthermore, most of the neurons in ventral horns, which appeared to be suffering from excitotoxicity during the early postnatal days, underwent apoptosis. However, the triggers of cellular abnormalization and neurodegenerative signaling were evident in the middle- to late-gestational stages, probably attributable to the amniotic fluid-induced in ovo milieu. In conclusion, we found that early neonatal loss of neurons in the ventral horn of exposed spinal cord affords novel insights into the pathophysiology of SBA-like leg dysfunction.http://dmm.biologists.org/content/10/12/1421Neural tube defectChicken modelSynaptic inputsGABAergic transmissionNeurodegenerationMotor dysfunction |
| spellingShingle | Md. Sakirul Islam Khan Hiroaki Nabeka Farzana Islam Tetsuya Shimokawa Shouichiro Saito Xuan Li Soichiro Kawabe Fumihiko Hamada Tetsuya Tachibana Seiji Matsuda Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model Disease Models & Mechanisms Neural tube defect Chicken model Synaptic inputs GABAergic transmission Neurodegeneration Motor dysfunction |
| title | Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model |
| title_full | Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model |
| title_fullStr | Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model |
| title_full_unstemmed | Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model |
| title_short | Early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida-like leg dysfunction in a chicken model |
| title_sort | early neonatal loss of inhibitory synaptic input to the spinal motor neurons confers spina bifida like leg dysfunction in a chicken model |
| topic | Neural tube defect Chicken model Synaptic inputs GABAergic transmission Neurodegeneration Motor dysfunction |
| url | http://dmm.biologists.org/content/10/12/1421 |
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