Abstract
The toxin beta-methylamino-l-alanine (BMAA) has been proposed to contribute to amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC) based on its ability to induce a similar disease phenotype in primates and its presence in cycad seeds, which constituted a dietary item in afflicted populations. Concerns about the apparent low potency of this toxin in relation to estimated levels of human ingestion led to a slowing of BMAA research. However, recent reports identifying potential new routes of exposure compel a re-examination of the BMAA/cycad hypothesis. BMAA was found to induce selective motor neuron (MN) loss in dissociated mixed spinal cord cultures at concentrations (∼ 30 μM) significantly lower than those previously found to induce widespread neuronal degeneration. The glutamate receptor antagonist NBQX prevented BMAA-induced death, implicating excitotoxic activation of AMPA/kainate receptors. Using microfluorimetric techniques, we further found that BMAA induced preferential [Ca2+]i rises and selective reactive oxygen species (ROS) generation in MNs with minimal effect on other spinal neurons. Cycad seed extracts also triggered preferential AMPA/kainate-receptor-dependent MN injury, consistent with the idea that BMAA is a crucial toxic component in this plant. Present findings support the hypothesis that BMAA may contribute to the selective MN loss in ALS/PDC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 244-252 |
| Number of pages | 9 |
| Journal | Experimental Neurology |
| Volume | 201 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 1 2006 |
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Keywords
- ALS
- ALS-PDC
- ALS/PDC
- AMPA
- Amyotrophic lateral sclerosis
- Ca
- Cell culture
- Cycad
- Glutamate
- Guam
- Motor neuron
- ROS
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
Cite this
BMAA selectively injures motor neurons via AMPA/kainate receptor activation. / Rao, Shyam; Banack, Sandra Anne; Cox, Paul Alan; Weiss, John H.
In: Experimental Neurology, Vol. 201, No. 1, 01.09.2006, p. 244-252.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - BMAA selectively injures motor neurons via AMPA/kainate receptor activation
AU - Rao, Shyam
AU - Banack, Sandra Anne
AU - Cox, Paul Alan
AU - Weiss, John H.
PY - 2006/9/1
Y1 - 2006/9/1
N2 - The toxin beta-methylamino-l-alanine (BMAA) has been proposed to contribute to amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC) based on its ability to induce a similar disease phenotype in primates and its presence in cycad seeds, which constituted a dietary item in afflicted populations. Concerns about the apparent low potency of this toxin in relation to estimated levels of human ingestion led to a slowing of BMAA research. However, recent reports identifying potential new routes of exposure compel a re-examination of the BMAA/cycad hypothesis. BMAA was found to induce selective motor neuron (MN) loss in dissociated mixed spinal cord cultures at concentrations (∼ 30 μM) significantly lower than those previously found to induce widespread neuronal degeneration. The glutamate receptor antagonist NBQX prevented BMAA-induced death, implicating excitotoxic activation of AMPA/kainate receptors. Using microfluorimetric techniques, we further found that BMAA induced preferential [Ca2+]i rises and selective reactive oxygen species (ROS) generation in MNs with minimal effect on other spinal neurons. Cycad seed extracts also triggered preferential AMPA/kainate-receptor-dependent MN injury, consistent with the idea that BMAA is a crucial toxic component in this plant. Present findings support the hypothesis that BMAA may contribute to the selective MN loss in ALS/PDC.
AB - The toxin beta-methylamino-l-alanine (BMAA) has been proposed to contribute to amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC) based on its ability to induce a similar disease phenotype in primates and its presence in cycad seeds, which constituted a dietary item in afflicted populations. Concerns about the apparent low potency of this toxin in relation to estimated levels of human ingestion led to a slowing of BMAA research. However, recent reports identifying potential new routes of exposure compel a re-examination of the BMAA/cycad hypothesis. BMAA was found to induce selective motor neuron (MN) loss in dissociated mixed spinal cord cultures at concentrations (∼ 30 μM) significantly lower than those previously found to induce widespread neuronal degeneration. The glutamate receptor antagonist NBQX prevented BMAA-induced death, implicating excitotoxic activation of AMPA/kainate receptors. Using microfluorimetric techniques, we further found that BMAA induced preferential [Ca2+]i rises and selective reactive oxygen species (ROS) generation in MNs with minimal effect on other spinal neurons. Cycad seed extracts also triggered preferential AMPA/kainate-receptor-dependent MN injury, consistent with the idea that BMAA is a crucial toxic component in this plant. Present findings support the hypothesis that BMAA may contribute to the selective MN loss in ALS/PDC.
KW - ALS
KW - ALS-PDC
KW - ALS/PDC
KW - AMPA
KW - Amyotrophic lateral sclerosis
KW - Ca
KW - Cell culture
KW - Cycad
KW - Glutamate
KW - Guam
KW - Motor neuron
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=33747191785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747191785&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2006.04.017
DO - 10.1016/j.expneurol.2006.04.017
M3 - Article
C2 - 16764863
AN - SCOPUS:33747191785
VL - 201
SP - 244
EP - 252
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -