Amelioration of cognitive ability in senescence-accelerated mouse prone 8 (SAMP8) by intra-bone marrow-bone marrow transplantation.
Bone marrow cells (BMCs) can increase the number of activated microglias, which play a central role in the inflammatory response in Alzheimer's disease (AD). Senescence-accelerated mouse (SAM) prone 8 (SAMP8) are widely used in various experiments because of cognitive deficits observed with age. In the present study, 4-month-old SAMP8 were reconstituted with BMCs of C57BL/6 mice by intra-bone marrow-bone marrow transplantation (IBM-BMT), which can reconstitute both donor-derived hemopoietic stem cells and mesenchymal stem cells. Three months after IBM-BMT, the impairment of spatial memory in SAMP8 was found to be ameliorated after analyzing the results of the water maze test. Although IL-1beta, IL-6 and iNOS increased and TGF-beta decreased in 7M SAMP8, IL-1beta, IL-6 and iNOS decreased while TGF-beta increased after IBM-BMT by RT-PCR. Moreover, oxidative stress-related heme oxygenase-1 (HO-1) increased in 7M SAMP8, but significantly decreased after IBM-BMT. In conclusion, this is the first report suggesting that the impaired cognitive ability of SAMP8 is ameliorated by IBM-BMT. It seems likely that decreases in IL-1beta, IL-6, iNOS and HO-1 are a result of the development of donor-derived BMCs.
Li
Ming
M
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Inaba
Muneo
M
Guo
Kequan
K
Abraham
Nader G
NG
Ikehara
Susumu
S
D000375:Aging; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000378:metabolism* / Q000601:surgery*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000378:metabolism / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1