Apr 15, 2004

Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity

Experimental Neurology
Matthew J LaVoieTeresa G Hastings

Abstract

Previous studies have demonstrated methamphetamine (METH)-induced toxicity to dopaminergic and serotonergic axons in rat striatum. Although several studies have identified the nature of reactive astrogliosis in this lesion model, the response of microglia has not been examined in detail. In this investigation, we characterized the temporal relationship of reactive microgliosis to neuropathological alterations of dopaminergic axons in striatum following exposure to methamphetamine. Adult male Sprague-Dawley rats were administered a neurotoxic regimen of methamphetamine and survived 12 h, or 1, 2, 4, and 6 days after treatment. Immunohistochemical methods were used to evaluate reactive changes in microglia throughout the brain of methamphetamine-treated rats, with a particular focus upon striatum. Pronounced morphological changes, indicative of reactive microgliosis, were evident in the brains of all methamphetamine-treated animals and were absent in saline-treated control animals. These included hyperplastic changes in cell morphology that substantially increased the size and staining intensity of reactive microglia. Quantitative analysis of reactive microglial changes in striatum demonstrated that these changes were most robust...Continue Reading

Mentioned in this Paper

Entire Brain
Establishment and Maintenance of Localization
Amphetamine
Phosphate buffers
Abnormal Degeneration
Immunoreactivity
Glial Fibrillary Acidic Protein
Neostriatum
Serotonin Measurement
Muscle Innervation, Function

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