Minocycline restores spatial but not fear memory in olfactory bulbectomized rats.
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.
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, Netherlands. y.e.borre@uu.nl
Yuliya
Y
Borre
Volkan
V
Sir
Sander
S
de Kivit
Koen G
KG
Westphal
Berend
B
Olivier
Ronald S
RS
Oosting
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000523:psychology; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000523:psychology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000601:surgery*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053583:Interleukin-1beta; D008911:Minocycline; D018697:Nootropic Agents; D012333:RNA, Messenger; C539355:CD68 protein, rat; D000097382:CD68 Molecule