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MCP-1 is elevated in hippocampus after trimethyl tin (TMT)-induced neuronal damage: biomarker of neural injury?
Little AR; O'Callaghan JP
Toxicologist 2001 Mar; 60(1):189
Monocyte chemoattractant protein (MCP)-1, a proinflammatory chemokine, recently has been reported to be up-regulated in many models of neuronal damage, including infection, axotomy, Alzheimer's (mouse model), excitotoxicity, and traumatic brain injury. A role for this chemokine in toxic injuries of the CNS has not been established, therefore, we evaluated the expression of MCP-1 following neuronal damage resulting from exposure to the prototypical hippocampal toxicant, TMT. Althought mediators of inflammation (TNF, IL-1, etc) are linked to neurological disease states, they are not, in general, associated with hippocampal damage and gliosis resulting from exposure to TMT. In the present study, however, we found a marked increase in the expression of MCP-1 after exposure of rats to TMT (8 mg/kg, i.p.). MCP-1 mRNA (assessed by RT-PCR) was elevated as early as 3 days post TMT, with peak increases (450%) observed at 21 days; the last timepoint studied. These effects of TMT on MCP-1 mRNA were confirmed by real-time Taqman analysis and were associated with increases in MCP-1 assessed by immunoblot and ELISA. Glucocorticoids (drinking water) suppressed the expression of MCP-1 without affecting TMT-induced gliosis; therefore, MCP-1 does not appear to mediate TMT-induced damage. Although the blood-brain barrier remained intact after TMT and blood could be ruled out as a source of MCP-1 expression in the brain, a source in the periphery for induction of brain MCP-1 cannot be excluded. This latter view is supported by the fact that systematic LPS (0.5 mg/kg) increases hippocampal MCP-1 mRNA in the absence of neuronal damage. MCP-1 may be a sensitive biomarker of neural injury but signals from peripheral target organs cannot be ruled out as sources of signals including brain expression of this chemokine.
Proteins; Traumatic injuries; Brain damage; Exposure levels; Neurological diseases
Issue of Publication
Neurotoxic Disorders; Neurotoxic Effects
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
Page last reviewed: July 9, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division