Sep 28, 1999

Oxidative stress is associated with region-specific neuronal death during thiamine deficiency

Journal of Neuropathology and Experimental Neurology
N Y CalingasanGary E Gibson

Abstract

Thiamine deficiency (TD) is a model of chronic impairment of oxidative metabolism and selective neuronal loss. TD leads to region-specific neuronal death and elevation of inducible nitric oxide synthase (iNOS) in macrophages/microglia in mouse brain. Identification of the initial site of neuronal death in the submedial thalamic nucleus allowed us to test the role of iNOS and oxidative stress in TD-induced neuronal death. The pattern of neuronal loss, which begins after 9 days of TD, overlapped with induction of the oxidative stress marker heme oxygenase-1 (HO-1) in microglia. Neuronal death and microglial HO-1 induction spread to engulf the whole thalamus after 11 days of TD. As in past studies, reactive iron and ferritin accumulated in microglia beginning on day 10. The lipid peroxidation product, 4-hydroxynonenal (HNE) accumulated in the remaining thalamic neurons only after 11 days of TD. These responses were not likely mediated by iNOS because HO-1 induction 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 useful model to help elucidate neuron-microglial ...Continue Reading

  • References
  • Citations72

References

  • We're still populating references for this paper, please check back later.

Mentioned in this Paper

Thanatophoric Dysplasia, Type 1
ISYNA1 gene
Blood - Brain Barrier Anatomy
Behavior, Animal
Thiamine Deficiency
Thalamic Nuclei
Triglyceride Storage Disease With Ichthyosis
Neurons
Brain
4-hydroxy-2-nonenal, (E)-isomer

About this Paper

Related Feeds

Astrocytes and Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood-Brain Barrier Transport in Neurodegeneration

The Blood-Brain Barrier (BBB) is essential in regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the BBB can be important for regulating drug movement in the brain and dysregulation of these processes may play a role in neurodegenerative disorders. Discover the latest research on BBB transporters here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.