Ny. Calingasan et al., Oxidative stress is associated with region-specific neuronal death during thiamine deficiency, J NE EXP NE, 58(9), 1999, pp. 946-958
Citations number
53
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Thiamine deficiency (TD) is a model of chronic impairment of oxidative meta
bolism and selective neuronal loss. TD leads to region-specific neuronal de
ath and elevation of inducible nitric oxide synthase (iNOS) in macrophages/
microglia in mouse brain. Identification of the initial site of neuronal de
ath in the submedial thalamic nucleus allowed us to test the role of iNOS a
nd oxidative stress in TD-induced neuronal death. The pattern of neuronal l
oss, which begins after 9 days of TD, overlapped with induction of the oxid
ative stress marker heme oxygenase-1 (HO-1) in microglia. Neuronal death an
d microglial HO-1 induction spread to engulf the whole thalamus after II da
ys of TD. As in past studies, reactive iron and ferritin accumulated in mic
roglia beginning on day 10. The lipid peroxidation product, 4-hydroxynonena
l (HNE) accumulated in the remaining thalamic neurons only after 11 days of
TD. These responses were not likely mediated by iNOS because HO-1 inductio
n and HNE accumulation were comparable in iNOS knockout mice and wild-type
controls. These results show that region and cell specific oxidative stress
is associated with selective neurodegeneration during TD. Thus, TD is a us
eful model to help elucidate neuron-microglial interaction in neurodegenera
tive diseases associated with oxidative stress.