Rosiglitazone attenuates the age-related changes in astrocytosis and the deficit in LTP.
Neuroinflammation is a significant and consistent feature of many neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). The greatest risk factor for neurodegenerative disorders is age and a proinflammatory phenotype in the aged brain is believed to contribute to these neurodegenerative conditions. In animal models, neuroinflammatory changes, characterized by increased microglial activation, have been associated with a loss of synaptic plasticity and here we show that treatment of aged rats with the PPARγ agonist, rosiglitazone, modulates the inflammatory changes and restores synaptic function. The evidence presented highlights an important role for astrocytes in inducing inflammatory changes and suggests that the age-related astrogliosis and astrocytosis is responsible for the increase in the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α). Magnetic resonance (MR) imaging revealed an age-related increase in T1 relaxation time and, importantly, treatment of aged rats with rosiglitazone reversed the age-related increases in astrogliosis and astrocytosis, TNF-α concentration and T1 relaxation time. The evidence indicates that the site of action for rosiglitazone is endothelial cells, and suggests that its effect on astrocytes is secondary to its effect on endothelial cells.
Cowley
Thelma R
TR
Trinity College Institute of Neuroscience and Physiology Department, Trinity College, Dublin 2, Ireland. tcowley@tcd.ie
O'Sullivan
Joan
J
Blau
Christoph
C
Deighan
Brian F
BF
Jones
Raasay
R
Kerskens
Christian
C
Richardson
Jill C
JC
Virley
David
D
Upton
Neil
N
Lynch
Marina A
MA
D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology* / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone