Minocycline inhibits neuronal death and glial activation induced by beta-amyloid peptide in rat hippocampus.
Minocycline, a second-generation tetracycline compound, has been examined as a neuroprotectant in beta-amyloid (A beta)-injected rat hippocampus. At 7 days post-injection, A beta(1-42) caused a significant loss of granule cell layer neurons (28% reduction) compared to control uninjected hippocampus. Hippocampal injection of A beta peptide also led to marked gliosis with numbers of microglia (increased by 26-fold) and immunoreactivity of astrocytes (increased by 11-fold) relative to control, as determined from immunohistochemical analysis. Intraperitoneal administration of minocycline significantly reduced neuronal loss induced by A beta(1-42) (by 80%) and also diminished numbers of microglia (by 69%) and astrocytes (by 36%) relative to peptide alone. Peptide injection increased expression of cyclooxygenase-2 (COX-2) in most (about 70%) of granule cells, a subset (about 20%) of microglia, but not in astrocytes; in the presence of minocycline, COX-2 immunostaining was abolished in microglia. The results from this study suggest that minocycline may have efficacy in the treatment of AD.
Ryu
Jae K
JK
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Franciosi
Sonia
S
Sattayaprasert
Prasongchai
P
Kim
Seung U
SU
McLarnon
James G
JG
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects; D051546:Cyclooxygenase 2; D005911:Gliosis; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D018696:Neuroprotective Agents; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D008911:Minocycline