Cognitive function in young and adult IL (interleukin)-6 deficient mice.
Interleukin-6 (IL-6) is a cytokine shown to affect brain function and to be involved in pathological neurodegenerative disorders such as Alzheimer's disease (AD). In the present study we investigated the cognitive function in transgenic mice not expressing IL-6 (IL-6 KO) and in wild type (WT) genotype at 4 and 12 months of age, using a passive avoidance and an eight-arm radial maze tasks. Motor function was quantified using an Animex apparatus. Hippocampal choline acetyltransferase (ChAT) activity was evaluated in both genotypes. No difference was observed in both genotypes for spontaneous motor activity. The mean latency (s) to re-enter the shock box, was similar in both young mutant and WT mice. However, a decreased sensitivity (50%) to scopolamine (1 mg/kg) in mutant compared to WT mice, was obtained. IL-6 KO mice exhibited a facilitation of radial maze learning over 30 days, in terms of a lower number of working memory errors and a higher percentage of animals reaching the criterion as compared with WT genotype tested at both ages. Furthermore, mutant mice, at the age of 12 months, showed a faster acquisition (22 days versus 30 days to reach the criterion). The pattern of arm entry exhibited by IL-6 KO mice showed a robust tendency to enter an adjacent arm at both ages, while WT only at the age of 4 months. ChAT activity was inversely correlated with memory performance. These findings suggest a possible involvement of IL-6 on memory processes, even if the mechanism remains still unclear.
Braida
Daniela
D
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32/A, 20129 Milan, Italy.
Sacerdote
Paola
P
Panerai
Alberto E
AE
Bianchi
Mauro
M
Aloisi
Anna Maria
AM
Iosuè
Stefania
S
Sala
Mariaelvina
M
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology
D015850:Interleukin-6; D018727:Muscarinic Antagonists; D012601:Scopolamine; D002795:Choline O-Acetyltransferase