Regional and age-related expression of gelatinases in the brains of young and old rats after treatment with kainic acid.
Due to the possible detrimental impact of local inflammatory responses in neurodegenerative disease, it was of interest to measure the expression of extracellular matrix-degrading enzymes, a group of proteases that are induced during an inflammatory response, in the brains of old and young animals in a model of neuronal death. Doses of kainic acid were administered that resulted in comparable hippocampal pyramidal neuron loss in young and old F344/BN hybrid rats, even though each age group received widely differing doses. Two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were differentially induced with respect to time after kainic acid in sensitive brain regions in both young and old rats. However, the elevation of MMP-9 in the temporal lobe 12 h after injection in old rats was significantly greater than that observed in young animals. These results suggest that early and late induction of MMPs may play a role in neuronal death and repair mechanisms, respectively, and that inflammatory mechanisms in the central nervous system (CNS) of old rats are exaggerated compared to young rats.
Zhang
J W
JW
University of South Florida College of Medicine, Department of Pharmacology and Therapeutics, Tampa, FL 33612-4799, USA.
Deb
S
S
Gottschall
P E
PE
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced
D018690:Excitatory Amino Acid Agonists; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D007608:Kainic Acid