Abstract
Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on motor neurons both in vitro and in vivo, but has limited efficacy in patients with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were treated by continuous IGF-1 delivery into the intrathecal space of the lumbar spinal cord. We found that the intrathecal administration of IGF-1 improved motor performance, delayed the onset of clinical disease, and extended survival in the G93A transgenic mice. Furthermore, it increased the expression of phosphorylated Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in these mice. Taken together, the results suggest that direct administration of IGF-1 into the intrathecal space may have a therapeutic benefit for ALS.
| Original language | English |
|---|---|
| Pages (from-to) | 61-68 |
| Number of pages | 8 |
| Journal | Journal of the Neurological Sciences |
| Volume | 235 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Aug 15 2005 |
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Keywords
- Akt
- Bcl-2
- ERK
- Motor neuron
- SOD1 mutation
- Spinal cord
ASJC Scopus subject areas
- Ageing
- Clinical Neurology
- Surgery
- Developmental Neuroscience
- Neurology
- Neuroscience(all)
Cite this
Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis. / Nagano, Isao; Ilieva, Hristelina; Shiote, Mito; Murakami, Tetsuro; Yokoyama, Masataka; Shoji, Mikio; Abe, Koji.
In: Journal of the Neurological Sciences, Vol. 235, No. 1-2, 15.08.2005, p. 61-68.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis
AU - Nagano, Isao
AU - Ilieva, Hristelina
AU - Shiote, Mito
AU - Murakami, Tetsuro
AU - Yokoyama, Masataka
AU - Shoji, Mikio
AU - Abe, Koji
PY - 2005/8/15
Y1 - 2005/8/15
N2 - Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on motor neurons both in vitro and in vivo, but has limited efficacy in patients with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were treated by continuous IGF-1 delivery into the intrathecal space of the lumbar spinal cord. We found that the intrathecal administration of IGF-1 improved motor performance, delayed the onset of clinical disease, and extended survival in the G93A transgenic mice. Furthermore, it increased the expression of phosphorylated Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in these mice. Taken together, the results suggest that direct administration of IGF-1 into the intrathecal space may have a therapeutic benefit for ALS.
AB - Insulin-like growth factor (IGF)-1 has been shown to have a protective effect on motor neurons both in vitro and in vivo, but has limited efficacy in patients with amyotrophic lateral sclerosis (ALS) when given subcutaneously. To examine the possible effectiveness of IGF-1 in a mouse model of familial ALS, transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) with a G93A mutation were treated by continuous IGF-1 delivery into the intrathecal space of the lumbar spinal cord. We found that the intrathecal administration of IGF-1 improved motor performance, delayed the onset of clinical disease, and extended survival in the G93A transgenic mice. Furthermore, it increased the expression of phosphorylated Akt and ERK in spinal motor neurons, and partially prevented motor neuron loss in these mice. Taken together, the results suggest that direct administration of IGF-1 into the intrathecal space may have a therapeutic benefit for ALS.
KW - Akt
KW - Bcl-2
KW - ERK
KW - Motor neuron
KW - SOD1 mutation
KW - Spinal cord
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UR - http://www.scopus.com/inward/citedby.url?scp=22844452812&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2005.04.011
DO - 10.1016/j.jns.2005.04.011
M3 - Article
C2 - 15990113
AN - SCOPUS:22844452812
VL - 235
SP - 61
EP - 68
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -