Early and specific expression of monocyte chemoattractant protein-1 in the thalamus induced by cortical injury.
For many years it has been known that retrograde degeneration of thalamic neurons occurs following damage to the cerebral cortex, however, the molecular mechanisms which control this process are unknown. Recent studies have demonstrated microglial activation in thalamic nuclei well before the onset of retrograde neuronal cell death. Activated monocytes and microglia synthesize factors detrimental to neuronal survival as well as phagocytose damaged and dying neurons. Our previous studies demonstrated that monocyte chemoattractant protein-1 (MCP-1), a beta chemokine which attracts cells of monocytic origin to sites of injury, is rapidly expressed in the brain following visual cortical lesions. The present study examined the expression of MCP-1 messenger RNA and protein in the thalamus following a visual cortical lesion. Aspiration lesions of visual cortex were made in adult mice. At specific times after lesion, brains were harvested and dissected into specific regions. MCP-1 message as detected using northern analysis was absent in uninjured brain, but was elevated in the ipsilateral thalamus as rapidly as 1 h following the lesion. In situ hybridization localized MCP-1 message to subpial glial cells of the lateral geniculate nucleus (LGN) of the ipsilateral thalamus after injury. ELISA showed that MCP-1 protein levels were significantly elevated in the ipsilateral thalamus at 6 h, peaked at 12 h, and remained above baseline levels for at least 1 week post lesion. In addition, anti-GFAP staining demonstrated activated astrocytes localized to the ipsilateral LGN at 24 and 72 h after injury. The early expression and regional localization of MCP-1 mRNA and protein strongly suggest that MCP-1 is a critical molecule in the regulation of thalamic retrograde neuronal degeneration.
Muessel
M J
MJ
Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow, Kansas City, KS 66160-7400, USA.
Berman
N E
NE
Klein
R M
RM
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000276:immunology; D001930:Brain Injuries / Q000276:immunology* / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000737:chemistry / Q000276:immunology; D009410:Nerve Degeneration / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D013788:Thalamus / Q000166:cytology / Q000276:immunology* / Q000503:physiopathology*; D014793:Visual Cortex / Q000293:injuries*
D018932:Chemokine CCL2; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger