Delayed, but prolonged increases in astrocytic clusterin (ApoJ) mRNA expression following acute cortical spreading depression in the rat: evidence for a role of clusterin in ischemic tolerance.
Clusterin is a sulfated glycoprotein produced by neurons and by resting and activated astrocytes that has several putative functions, including protective responses to brain injury. Cortical spreading depression (CSD) is a powerful yet largely benign stimulus that acutely is capable of providing long-lasting ischemic tolerance. The current study investigated possible alterations in expression of clusterin mRNA in the cerebral cortex of the rat at various times after unilateral CSD. Using semiquantitative in situ hybridization histochemistry, significant increases (30-100%; P< or =0.05) in clusterin mRNA were detected in layers I-III and IV-VI of the ipsilateral cortex at 1, 2, 7 and 14 (layers I-III only) days after CSD. Transcript levels in the ipsilateral cortex were again equivalent to contralateral (control) levels at 28 days after CSD. These molecular anatomical studies also revealed that both neurons and nonneuronal cells (presumed reactive astrocytes) increased their expression of clusterin mRNA following CSD. Notably the time-course of increases in clusterin mRNA after CSD (1-14 days) overlaps that during which CSD reportedly provides neuroprotection against subsequent cerebral ischemia. These findings along with other evidence suggest that increased clusterin production and secretion, particularly by astrocytes, could be neuroprotective-perhaps via one or more of its putative actions that include inhibition of complement activation and cytolysis, effects on chemotaxis and apoptosis, and actions as an anti-stress protein chaperone.
Wiggins
Amanda K
AK
Howard Florey Institute of Experimental Physiology and Medicine and Department of Medicine, Austin and Repatriation Medical Centre, The University of Melbourne, Victoria 3010, Australia.
Shen
Pei-Juan
PJ
Gundlach
Andrew L
AL
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002545:Brain Ischemia / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000166:cytology; D051152:Clusterin; D013181:Cortical Spreading Depression / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics*; D019194:Ischemic Preconditioning; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C498500:Clu protein, rat; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger