Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat.
It has been suggested that inflammatory processes may play a role in the development of Alzheimer's disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of aggregated beta-amyloid (Abeta) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Abeta injections. Withdrawal of ibuprofen treatment from aggregated Abeta-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Abeta-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Abeta injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.
Richardson
R L
RL
School of Psychology, University of Ulster, Shore Road, Newtownabbey, Co. Antrim, BT37 0QB, N. Ireland, UK.
Kim
E-M
EM
Shephard
R A
RA
Gardiner
T
T
Cleary
J
J
O'Hare
E
E
D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007052:Ibuprofen / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008845:Microinjections; D023421:Models, Animal; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007052:Ibuprofen