Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

Yasuyuki Ohta, Makiko Nagai, Tetsuya Nagata, Tetsuro Murakarni, Isao Nagano, Hisashi Narai, Tomoko Kurata, Mito Shiote, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

We investigated three steps of neural precursor cell activation- proliferation, migration, and differentiation-in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.

Original languageEnglish
Pages (from-to)980-992
Number of pages13
JournalJournal of Neuroscience Research
Volume84
Issue number5
DOIs
Publication statusPublished - Oct 2006

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Spinal Injections
Fibroblast Growth Factor 2
Bromodeoxyuridine
Epidermal Growth Factor
Spinal Cord
Transgenic Mice
Nestin
Genes
Neural Cell Adhesion Molecules
Ependyma
Anterior Horn Cells
Nuclear Antigens
Glial Fibrillary Acidic Protein
Amyotrophic Lateral Sclerosis
Horns
Astrocytes
Cell Proliferation
Calcium
Therapeutics

Keywords

  • Amyotrophic lateral sclerosis
  • Epidermal growth factor
  • Fibroblast growth factor 2
  • Neural precursor cells
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene. / Ohta, Yasuyuki; Nagai, Makiko; Nagata, Tetsuya; Murakarni, Tetsuro; Nagano, Isao; Narai, Hisashi; Kurata, Tomoko; Shiote, Mito; Shoji, Mikio; Abe, Koji.

In: Journal of Neuroscience Research, Vol. 84, No. 5, 10.2006, p. 980-992.

Research output: Contribution to journalArticle

Ohta, Yasuyuki ; Nagai, Makiko ; Nagata, Tetsuya ; Murakarni, Tetsuro ; Nagano, Isao ; Narai, Hisashi ; Kurata, Tomoko ; Shiote, Mito ; Shoji, Mikio ; Abe, Koji. / Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene. In: Journal of Neuroscience Research. 2006 ; Vol. 84, No. 5. pp. 980-992.
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AU - Nagata, Tetsuya

AU - Murakarni, Tetsuro

AU - Nagano, Isao

AU - Narai, Hisashi

AU - Kurata, Tomoko

AU - Shiote, Mito

AU - Shoji, Mikio

AU - Abe, Koji

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AB - We investigated three steps of neural precursor cell activation- proliferation, migration, and differentiation-in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.

KW - Amyotrophic lateral sclerosis

KW - Epidermal growth factor

KW - Fibroblast growth factor 2

KW - Neural precursor cells

KW - Spinal cord

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