Abstract
Impaired axonal transport of the fast or slow component has been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), animal models for ALS, and familial ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) transgenic mice. However, little is known about the impairment of axonal transport in mutant SOD1 transgenic mice. This is the first electron microscopic investigation of the axon hillock (AH) and the initial segment (IS) of anterior horn cells in the spinal cord of transgenic mice expressing the G93A mutant human SOD1, and it was launched with a view toward examining whether the axonal transport is impaired in this region. Six transgenic mice were killed at ages ranging from the presymptomatic to symptomatic stages. Six age-matched non-transgenic wild-type mice served as controls. In the non-transgenic mice, 91 AH and IS were observed, but those with increased neurofilaments or mitochondria were rarely found. In the transgenic mice, 95 AH and IS directly emanating from normal-looking large anterior horn cells were seen. AH and IS with increased neurofilaments or, to a lesser extent, increased mitochondria, and round-shaped mitochondria in particular, were more frequently observed, even at the early presymptomatic stage, than in the controls, and the frequency increased with time through the presymptomatic stages. On the other hand, the somata of large motor neurons directly connected with the axons did not exhibit any abnormal accumulation of neurofilaments or mitochondria. These findings suggest that both the slow axonal transport of neurofilaments and the fast axonal transport of mitochondria are impaired in AH and IS before the onset of disease in this animal model.
| Original language | English |
|---|---|
| Pages (from-to) | 48-56 |
| Number of pages | 9 |
| Journal | Acta Neuropathologica |
| Volume | 110 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2005 |
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Keywords
- Amyotrophic lateral sclerosis
- Axonal transport (fast and slow)
- G93A transgenic mice
- SOD1 mutation
- Ultrastructure
ASJC Scopus subject areas
- Clinical Neurology
- Pathology and Forensic Medicine
- Neuroscience(all)
Cite this
Impairment of axonal transport in the axon hillock and the initial segment of anterior horn neurons in transgenic mice with a G93A mutant SOD1 gene. / Sasaki, Shoichi; Warita, Hitoshi; Abe, Koji; Iwata, Makoto.
In: Acta Neuropathologica, Vol. 110, No. 1, 07.2005, p. 48-56.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impairment of axonal transport in the axon hillock and the initial segment of anterior horn neurons in transgenic mice with a G93A mutant SOD1 gene
AU - Sasaki, Shoichi
AU - Warita, Hitoshi
AU - Abe, Koji
AU - Iwata, Makoto
PY - 2005/7
Y1 - 2005/7
N2 - Impaired axonal transport of the fast or slow component has been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), animal models for ALS, and familial ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) transgenic mice. However, little is known about the impairment of axonal transport in mutant SOD1 transgenic mice. This is the first electron microscopic investigation of the axon hillock (AH) and the initial segment (IS) of anterior horn cells in the spinal cord of transgenic mice expressing the G93A mutant human SOD1, and it was launched with a view toward examining whether the axonal transport is impaired in this region. Six transgenic mice were killed at ages ranging from the presymptomatic to symptomatic stages. Six age-matched non-transgenic wild-type mice served as controls. In the non-transgenic mice, 91 AH and IS were observed, but those with increased neurofilaments or mitochondria were rarely found. In the transgenic mice, 95 AH and IS directly emanating from normal-looking large anterior horn cells were seen. AH and IS with increased neurofilaments or, to a lesser extent, increased mitochondria, and round-shaped mitochondria in particular, were more frequently observed, even at the early presymptomatic stage, than in the controls, and the frequency increased with time through the presymptomatic stages. On the other hand, the somata of large motor neurons directly connected with the axons did not exhibit any abnormal accumulation of neurofilaments or mitochondria. These findings suggest that both the slow axonal transport of neurofilaments and the fast axonal transport of mitochondria are impaired in AH and IS before the onset of disease in this animal model.
AB - Impaired axonal transport of the fast or slow component has been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), animal models for ALS, and familial ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) transgenic mice. However, little is known about the impairment of axonal transport in mutant SOD1 transgenic mice. This is the first electron microscopic investigation of the axon hillock (AH) and the initial segment (IS) of anterior horn cells in the spinal cord of transgenic mice expressing the G93A mutant human SOD1, and it was launched with a view toward examining whether the axonal transport is impaired in this region. Six transgenic mice were killed at ages ranging from the presymptomatic to symptomatic stages. Six age-matched non-transgenic wild-type mice served as controls. In the non-transgenic mice, 91 AH and IS were observed, but those with increased neurofilaments or mitochondria were rarely found. In the transgenic mice, 95 AH and IS directly emanating from normal-looking large anterior horn cells were seen. AH and IS with increased neurofilaments or, to a lesser extent, increased mitochondria, and round-shaped mitochondria in particular, were more frequently observed, even at the early presymptomatic stage, than in the controls, and the frequency increased with time through the presymptomatic stages. On the other hand, the somata of large motor neurons directly connected with the axons did not exhibit any abnormal accumulation of neurofilaments or mitochondria. These findings suggest that both the slow axonal transport of neurofilaments and the fast axonal transport of mitochondria are impaired in AH and IS before the onset of disease in this animal model.
KW - Amyotrophic lateral sclerosis
KW - Axonal transport (fast and slow)
KW - G93A transgenic mice
KW - SOD1 mutation
KW - Ultrastructure
UR - http://www.scopus.com/inward/record.url?scp=23644437653&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644437653&partnerID=8YFLogxK
U2 - 10.1007/s00401-005-1021-9
DO - 10.1007/s00401-005-1021-9
M3 - Article
C2 - 15920660
AN - SCOPUS:23644437653
VL - 110
SP - 48
EP - 56
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 1
ER -