GRK5 deficiency exaggerates inflammatory changes in TgAPPsw mice.
BACKGROUND
Deficiency of membrane G-protein coupled receptor (GPCR) kinase-5 (GRK5) recently has been linked to early AD pathogenesis, and has been suggested to contribute to augmented microglial activation in vitro by sensitizing relevant GPCRs. However, GRK5 deficient mice did not show any signs of microgliosis, except for their moderate increase in axonal defects and synaptic degenerative changes during aging. We have speculated that one possible reason for the absence of microgliosis in these animals might be due to lack of an active inflammatory process involving activated GPCR signaling, since GRKs only act on activated GPCRs. The objective of this study was to determine whether the microgliosis is exaggerated in TgAPPsw (Tg2576) mice also deficient in GRK5, in which fibrillar beta-amyloid (Abeta) and an active inflammatory process involving activated GPCR signaling are present.


METHODS
Both quantitative and qualitative immunochemistry methods were used to evaluate the microgliosis and astrogliosis in these animals.


RESULTS
We found that inactivation of one copy of the GRK5 gene in the TgAPPsw mice resulted in approximately doubled extent of microgliosis, along with significantly exaggerated astrogliosis, in both hippocampus and cortex of the aged animals. Consistent with previous observations, the activated microglia were located primarily near or surrounding the fibrillar Abeta deposits.


CONCLUSIONS
The results demonstrate that GRK5 deficiency in vivo significantly exaggerates microgliosis and astrogliosis in the presence of an inflammatory initiator, such as the excess fibrillar Abeta and the subsequent active inflammatory reactions in the TgAPPsw mice.
Li
Longxuan
L
Lab, for Alzheimer's Disease & Aging Res,, VA Med, Center, Kansas City, MO 64128, USA. longxuanlee2006@yahoo.com
Liu
Jun
J
Suo
William Z
WZ
D000544:Alzheimer Disease / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D017931:DNA Primers; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000172:deficiency*; D005838:Genotype; D007249:Inflammation / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D054774:G-Protein-Coupled Receptor Kinase 5; C517895:Grk5 protein, mouse; D017493:Leukocyte Common Antigens