Mutant mice with small amounts of BubR1 display accelerated age-related gliosis.
Aging is an intricate biological process thought to involve multiple molecular pathways. The spindle assembly checkpoint protein BubR1 has recently been implicated in aging since mutant mice that have small amounts of this protein (BubR1(H/H) mice) develop several early aging-associated phenotypes. The phenotype within the brain of BubR1(H/H) mice has not yet been established. Here we show that BubR1(H/H) mice exhibit features of age-related cerebral degeneration. We found that glial fibrillary acidic protein (GFAP), a marker of reactive astrogliosis, was expressed at increased levels in the cortex and thalamus of BubR1(H/H) mice as early as 1 month of age. Furthermore, CD11b, a marker of microgliosis, was markedly elevated in the cortex and hippocampus of BubR1(H/H) mice at 5 months of age. Levels of both GFAP and CD11b further increased with age. Our results demonstrate that BubR1 acts to prevent cerebral gliosis of both astrocytes and microglial cells, and suggest a role for BubR1 in the aging process of the brain.
Hartman
Tyler K
TK
Department of Pediatric/Adolescent Medicine, Mayo Clinic, College of Medicine, Rochester, MN 55905, United States.
Wengenack
Thomas M
TM
Poduslo
Joseph F
JF
van Deursen
Jan M
JM
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018797:Cell Cycle Proteins; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases
C584278:Bub1b protein, mouse; D039481:CD11b Antigen; D018797:Cell Cycle Proteins; D005904:Glial Fibrillary Acidic Protein; D011494:Protein Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases