Up-regulation of cystatin C expression in the murine hippocampus following perforant path transections.
Cystatins are endogenous cysteine protease inhibitors that modulate the turnover of intracellular and extracellular proteins. These inhibitors are strongly implicated in a variety of pathological processes such as tumor metastasis and many degenerating CNS disorders. Here we report the expression of cystatin C, a major cysteine protease inhibitor of mammalian animals, in the murine hippocampus at 3, 7, 15 and 30 days following perforant path transections. Northern blot analysis showed that cystatin C transcripts were up-regulated in a transient manner with a significant increase at 7 and 15 days post-lesion (219% and 185% of control, respectively) in the rat hippocampus after entorhinal deafferentation. In situ hybridization and immunohistochemistry confirmed the time-dependent up-regulation of both cystatin C mRNA and protein expressions in a mouse model which initiated at 3 days post-lesion, reached maximal levels 7-15 days post-lesion, and remained slightly elevated by day 30 post-lesion. The modulation of cystatin C expression was observed to occur specifically in the entorhinally denervated zones: the stratum lacunosum-moleculare of the hippocampus and the outer molecular layer of the dentate gyrus. Double labeling by either a combination of in situ hybridization for cystatin C with immunohistochemistry for glial fibrillary acidic protein or double immunofluorescence staining for both proteins in mouse hippocampus at 7 and 15 days post-lesion revealed that most cystatin C-expressing cells are astrocytes. From these results we suggest that the spatiotemporal up-regulation of cystatin C in the hippocampus is induced by entorhinal deafferentation and that cystatin C may be involved in the astroglia-mediated neural plasticity events in the hippocampus following perforant path transections.
Ying
G-X
GX
Key Laboratory of Neurobiology, Shanghai Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Huang
C
C
Jiang
Z-H
ZH
Liu
X
X
Jing
N-H
NH
Zhou
C-F
CF
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015152:Blotting, Northern; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity / Q000502:physiology; D019635:Neurosurgical Procedures; D019580:Perforant Pathway / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*
C525031:Cst3 protein, mouse; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger