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Mem 97 c17-cycad-induced neurodegeneration in a mouse model of als-pdc. sold by nybgshop.org for $4.99

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This purchase only includes chapter 17 of this title.

AbstractThe strongest epidemiological correlate for amyotrophic lateral sclerosis-Parkinsonism dementia complex (ALS-PDC) is consumption of the seed of the cycad (Cycas micronesica) known to contain various toxins. Much previous work focused on cycasin and its aglycone methylazoxymethanol (MAM) as well as on various excitatory amino acids, notably β-N-oxalylamino-L-alanine (BOAA) and β-methylamino-alanine (BMAA). None of these compounds is contained in signiï¬?cant concentrations in cycad seed “chipsâ€? prepared by traditional Chamorro washing procedures. Cycasin/MAM and BOAA do not induce neurological symptoms resembling ALS-PDC. BMAA, a weak N-methyl-D-aspartate (NMDA) receptor agonist, has also routinely failed to induce ALS-PDC–like outcomes. Recent work by Cox and colleagues suggests that BMAA contained in cycads reaches levels that are able to induce neurodegeneration in ALS-PDC following biomagniï¬?cation up the food chain. We have reexamined the “cycad hypothesisâ€? for ALS-PDC in in vivo experiments on adult male mice fed washed cycad pellets (up to 25% of total diet).The cycad pellets contained nil to trace concentrations of cycasin/MAM, BOAA, or BMAA. Cycad-fed mice rapidly developed typical motor and cognitive behavioral phenotypes strongly resembling both amyotrophic lateral sclerosis and parkinsonian dementia. Histological analysis of the central nervous systems of these mice showed neuronal loss with apoptosis, as well as the presence of activated astrocytes in the spinal cord, substantia nigra, hippocampus, cortex, and olfactory bulb. In contrast, pure BMAA at high dosages did not give rise to behavioral deï¬?cits or pathological outcomes. Other neurotoxins such as methionine sulfoximine or 3-nitropropionic acid showed spinal cord–or basal ganglia–associated deï¬?cits, respectively. BMAA thus appears unlikely to play a signiï¬?cant role in ALS-PDC. The bound BMAA reported in restricted regions o




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