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.
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Jae K
JK
Ryu
Sonia
S
Franciosi
Prasongchai
P
Sattayaprasert
Seung U
SU
Kim
James G
JG
McLarnon
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