Abstract
We investigated the effects of minocycline, a microglia suppressant, on olfactory bulbectomized (OBX) rats, a model of cognitive and behavioral impairments arising from neurodegenerative processes. Previously, we demonstrated that the major OBX-induced behavioral and cognitive impairments develop between day 3 and 7 following bulbectomy. Here we show that the onset of these cognitive changes parallel in time with signs of microglia activation (increased mRNA levels of IL-1β and CD68) in hippocampus. Next, rats were treated with minocycline (50mg/kg, i.p.) once daily for 4 weeks. OBX surgery was done at day 3 of drug treatment. Animals were tested in a battery of behavioral assays: open field, passive avoidance (fear learning and memory-acquired prior to OBX) and T-maze (spatial memory, conducted post bulbectomy). Minocycline normalized OBX-induced hyperactivity in the open field. Minocycline failed to prevent fear memory loss, but protected the OBX rats against hippocampal-dependent spatial memory deficit. Our findings suggest that treatment with minocycline may be effective in the early phase of a neurodegenerative disease.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / genetics
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Antigens, Differentiation, Myelomonocytic / metabolism
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Avoidance Learning / drug effects
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Behavior, Animal / drug effects*
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Cognition / drug effects
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Cognition Disorders / drug therapy*
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Cognition Disorders / etiology
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Cognition Disorders / genetics
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Cognition Disorders / psychology
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Disease Models, Animal
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Fear / drug effects*
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Hippocampus / drug effects
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Hippocampus / metabolism
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Injections, Intraperitoneal
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Male
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Memory / drug effects*
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Memory Disorders / drug therapy*
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Memory Disorders / etiology
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Memory Disorders / genetics
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Memory Disorders / psychology
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Microglia / drug effects
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Microglia / metabolism
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Minocycline / administration & dosage
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Minocycline / pharmacology*
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Neuropsychological Tests
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Nootropic Agents / administration & dosage
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Nootropic Agents / pharmacology*
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Olfactory Bulb / surgery*
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Up-Regulation
Substances
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD68 protein, rat
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Interleukin-1beta
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Nootropic Agents
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RNA, Messenger
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Minocycline