Focal cerebral ischemia upregulates SHP-1 in reactive astrocytes in juvenile mice.
The role of the tyrosine phosphatase SHP-1 in the hematopoietic system has been well studied; however, its role in the central nervous system (CNS) response to injury is not well understood. Previous studies in our laboratory have demonstrated increased immunoreactivity for SHP-1 in a subset of reactive astrocytes that do not appear to enter the cell cycle following deafferentation of the chicken auditory brainstem. In order to determine whether mammalian astrocytes also upregulate SHP-1 immunoreactivity following CNS injury, a mouse model of focal cerebral ischemia was utilized to study SHP-1 expression. The brains of 3-week-old mice were analyzed at four time points following permanent middle cerebral artery occlusion (MCAO): 1, 3, 7, and 14 days. Our results demonstrate consistent infarct volumes within surgical groups, and infarct volumes decrease as a function of time from 1 day (maximum infarct volume) to 14 days (minimum infarct volume) post-MCAO. In addition, SHP-1 protein levels are upregulated following cerebral ischemia and this increase peaks at 7 days post-MCAO. Analysis of confocal images further reveals that immunoreactivity for SHP-1 occurs predominantly in GFAP+ reactive astrocytes, although a small percentage of F4-80+ microglia are also double labeled for SHP-1 at early times post-MCAO. These SHP-1+ reactive astrocytes do not appear to enter the cell cycle (as defined by PCNA immunoreactivity), confirming our previous studies in the avian auditory brainstem. These results suggest that SHP-1 plays an important role in the regulation of glial activation and proliferation in the ischemic CNS.
Wishcamper
Celine A
CA
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, The University of Montana, Skaggs Building, Room 304, Missoula 59812, USA.
Brooks
Diane M
DM
Douglas Coffin
J
J
Lurie
Diana I
DI
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018613:Microscopy, Confocal; D020768:Middle Cerebral Artery / Q000502:physiology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse