Alterations in ApoE and ApoJ in relation to degeneration and regeneration in a mouse model of entorhinal cortex lesion.
Apolipoproteins are primarily involved in the transport of lipid and cholesterol within the central nervous system (CNS) and are thought to play a role in synaptic remodeling, repair, and regeneration after brain injury. In the present study, alterations in apolipoproteins E (apoE) and J (apoJ) were examined in the molecular layers of the dentate gyrus after unilateral chemical lesioning of the entorhinal cortex (ECL), at days 0, 1, 3, 7, 28, and 90 days following injury. Alterations in immunostaining for these proteins were assessed in relation to accumulation of silver-labeled degeneration products and alterations in synaptophysin and GAP-43 immunoreactivity. Quantitative analysis of synaptophysin and GAP-43 immunostaining highlighted synaptic loss and fiber degeneration initially (3-7 days post-ECL), with subsequent terminal sprouting and reactive synaptogenesis occurring at longer survival periods (28-90 days post-ECL). Increased apoE and apoJ immunoreactivity was evident first within the neuropil (*P < 0.05 and **P < 0.01) followed by intense glial staining by day 7 post-ECL. By day 28 apoE and apoJ immunostaining had returned almost to baseline levels. However, at day 90 post-ECL, neuropil apoE and apoJ immunoreactivity was dramatically increased compared to contralateral levels (**P < 0.01 and ***P < 0.0001, respectively). Silver-labeled degeneration products were found to be in abundance at day 3 postlesion; however, by day 7 this was reduced leaving only a thin band of material within the MML and at day 90 post-ECL, dentate silver staining was similar to that of controls. The results indicate that apoE and apoJ are upregulated after injury and parallel clearance of cholesterol and lipid debris from the site of injury. This coordinated alteration in apolipoproteins may redistribute lipid material to sprouting fibers to promote neurite extension and may play an important role in long-term plasticity changes following injury.
White
F
F
Wellcome Surgical Institute, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow, G61 1QH, United Kingdom.
Nicoll
J A
JA
Horsburgh
K
K
D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000378:metabolism*; D051152:Clusterin; D018891:Dentate Gyrus / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000502:physiology* / Q000503:physiopathology; D007839:Functional Laterality; D019922:GAP-43 Protein / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism*; D007051:Ibotenic Acid; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000032:analysis / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009411:Nerve Endings / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D013569:Synapses / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism
D001057:Apolipoproteins E; C495243:Clu protein, mouse; D051152:Clusterin; D019922:GAP-43 Protein; D006023:Glycoproteins; D018832:Molecular Chaperones; D016708:Synaptophysin; D007051:Ibotenic Acid