2003 Fiscal Year Annual Research Report

グリア由来神経栄養因子としてのL-セリン供給機構の解明と神経再生への応用

Research Project

Project/Area Number	13558092
Research Institution	HOKKAIDO UNIVERSITY
Principal Investigator	渡辺雅彦北海道大学, 大学院・医学研究科, 教授 (70210945)
Keywords	セリン / シュワン細胞 / 坐骨神経 / 損傷 / 脊髄 / 3PGDH / 再生
Research Abstract	非必須アミノ酸の1つであるL-セリンは、培養ニューロンに対して強力な神経栄養効果を及ぼす。L-セリン合成酵素3-phosphoglycerate dehydrogenase (3PGDH)の発現解析から、ニューロンにはセリン合成能がなく、脳内では専らグリア細胞が合成していることを以前明らかにしている。昨年度は、L-セリンの輸送機構を明らかにするために、L-セリン輸送能を持つ中性アミノ酸トランスポーターASCT1に着目し、その特異抗体を作成し、成熟脳において発現細胞を解析した。その結果、胎児期から成熟期に至るまで、ASCT1は3PGDHを発現するグリアに共発現することを見い出した。この成果は、脳においてグリア細胞がセリンの脳内合成だけでなく、その供給の中心的役割を担っていることが示唆された。本年度は、この成果を脊髄および末梢神経系にも適用できるか、さらに神経損傷後のセリン合成酵素の発現局在変化を追求した。坐骨神経を通る感覚性および運動性経路に沿って3PGDHの細胞発現を検討したところ、後根神経節の衛星細胞、髄鞘形成するシュワン細胞、運動ニューロン周囲のニューロン周囲希突起膠細胞の3種に強い陽性反応を認め、神経線維束の間に介在する線維芽細胞にも若干の発現が観察された。一方、ニューロンの細胞体や軸索には、全く3PGDHの発現は検出できなかった。挫滅損傷を与えると、シュワン細胞と線維芽細胞の3PGDHの発現が転写および翻訳レベルで増強したが、ニューロンや軸索、マクロファージは陰性のままであった。以上の結果より、末梢神経系においても、セリンの合成はニューロンにはなく、その周囲の支持細胞(グリア細胞や線維芽細胞)が担っており、機能維持や損傷後の神経再生に寄与している可能性が示唆された。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Sakai, K.: "Neutral amino acid transporter ASCT1 is preferentially expressed in L-Ser synthetic/storing glial cells in the mouse with transient expression in developing capillaries"J.Neurosci.. 23. 550-560 (2003)
[Publications] Kakizawa, S.: "Effects of Insulin-like Growth Factor I on Climbing Fiber Synapse Elimination during Cerebellar Development"Eur.J.Neurosci. 17. 545-554 (2003)
[Publications] Fukaya, M.: "Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum in targeted NR1 knockout mice"Proc.Natl.Acad.Sci.USA. 100. 4855-4860 (2003)
[Publications] Shibata, T.: "Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord"Dev.Brain Res.. 140. 263-268 (2003)
[Publications] Somogyi, P.: "High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurones in the rat hippocampus"Eur.J.Neurosci.. 17. 2503-2520 (2003)
[Publications] Miyazaki, T.: "Developmental switching of vesicular glutamate transporters at parallel fiber-Purkinje cell synapses"Eur.J.Neurosci. 17. 2563-2572 (2003)
[Publications] Sassoe-Pngnetto, M.: "Organization of postsynaptic density proteins and glutamate receptors in axodendritic and dendrodendritic synapses of the rat olfactory bulb"J.Comp.Neurol.. 463. 237-248 (2003)
[Publications] Miyata, M.: "Role of thalamic phospholipase Cb4 mediated by metabotropic glutamate receptor type 1 in inflammatory pain"J.Neurosci. 23. 8098-8108 (2003)
[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons"Dev.Biol.. 263. 216-230 (2003)
[Publications] Takahashi, Y.: "Autoantibodies to NMDA receptor in patients with chronic formsof epilepsia partialis continua"Neurol.. 61. 891-896 (2003)
[Publications] Yamashita, N.: "Selective expression of L-serine synthetic enzyme 3PGDH in Schwann cells, perineuronal glia, and endoneurial fibroblasts along sciatic nerves and its upregulation after crush injury"Arch.Histol.Cytol.. (印刷中).
[Publications] Hama, K.: "Lysophosphatidic acid and autaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1"J.Biol.Chem.. (印刷中).
[Publications] Ferraguti, F.: "Immunolocalization of metabotropic glutamate receptor 1a (mGluR1a) in distinct classes of interneuron in the CA1 region of the rat hippocampus"Hippocampus. (印刷中).
[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-accociated PDZ proteins in developing cortical neurons"Dev Biol. (印刷中).
[Publications] Kinoshita, N.: "Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes"Genes Cells. (印刷中).
[Publications] Miyazaki, M.: "P/Q-type Ca^<2+> channel α1A regulates synaptic competition on developing cerebellar Purkinje cells"J.Neurosci.. (印刷中).

2003 Fiscal Year Annual Research Report

グリア由来神経栄養因子としてのL-セリン供給機構の解明と神経再生への応用

Principal Investigator

渡辺 雅彦 北海道大学, 大学院・医学研究科, 教授 (70210945)

Research Products

[Publications] Sakai, K.: "Neutral amino acid transporter ASCT1 is preferentially expressed in L-Ser synthetic/storing glial cells in the mouse with transient expression in developing capillaries"J.Neurosci.. 23. 550-560 (2003)

[Publications] Kakizawa, S.: "Effects of Insulin-like Growth Factor I on Climbing Fiber Synapse Elimination during Cerebellar Development"Eur.J.Neurosci. 17. 545-554 (2003)

[Publications] Fukaya, M.: "Retention of NMDA receptor NR2 subunits in the lumen of endoplasmic reticulum in targeted NR1 knockout mice"Proc.Natl.Acad.Sci.USA. 100. 4855-4860 (2003)

[Publications] Shibata, T.: "Transient neonatal expression of NR2B/2D subunit mRNAs of the N-methyl-D-aspartate receptor in the parasympathetic preganglionic neurons in the rat spinal cord"Dev.Brain Res.. 140. 263-268 (2003)

[Publications] Somogyi, P.: "High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurones in the rat hippocampus"Eur.J.Neurosci.. 17. 2503-2520 (2003)

[Publications] Miyazaki, T.: "Developmental switching of vesicular glutamate transporters at parallel fiber-Purkinje cell synapses"Eur.J.Neurosci. 17. 2563-2572 (2003)

[Publications] Sassoe-Pngnetto, M.: "Organization of postsynaptic density proteins and glutamate receptors in axodendritic and dendrodendritic synapses of the rat olfactory bulb"J.Comp.Neurol.. 463. 237-248 (2003)

[Publications] Miyata, M.: "Role of thalamic phospholipase Cb4 mediated by metabotropic glutamate receptor type 1 in inflammatory pain"J.Neurosci. 23. 8098-8108 (2003)

[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons"Dev.Biol.. 263. 216-230 (2003)

[Publications] Takahashi, Y.: "Autoantibodies to NMDA receptor in patients with chronic formsof epilepsia partialis continua"Neurol.. 61. 891-896 (2003)

[Publications] Yamashita, N.: "Selective expression of L-serine synthetic enzyme 3PGDH in Schwann cells, perineuronal glia, and endoneurial fibroblasts along sciatic nerves and its upregulation after crush injury"Arch.Histol.Cytol.. (印刷中).

[Publications] Hama, K.: "Lysophosphatidic acid and autaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1"J.Biol.Chem.. (印刷中).

[Publications] Ferraguti, F.: "Immunolocalization of metabotropic glutamate receptor 1a (mGluR1a) in distinct classes of interneuron in the CA1 region of the rat hippocampus"Hippocampus. (印刷中).

[Publications] Jourdi, H.: "Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-accociated PDZ proteins in developing cortical neurons"Dev Biol. (印刷中).

[Publications] Kinoshita, N.: "Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes"Genes Cells. (印刷中).

[Publications] Miyazaki, M.: "P/Q-type Ca^<2+> channel α1A regulates synaptic competition on developing cerebellar Purkinje cells"J.Neurosci.. (印刷中).

渡辺雅彦北海道大学, 大学院・医学研究科, 教授 (70210945)