Elsevier

Neuroscience Letters

Volume 465, Issue 1, 6 November 2009, Pages 36-40
Neuroscience Letters

Amelioration of cognitive ability in senescence-accelerated mouse prone 8 (SAMP8) by intra-bone marrow-bone marrow transplantation

https://doi.org/10.1016/j.neulet.2009.09.001Get rights and content

Abstract

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-1β, IL-6 and iNOS increased and TGF-β decreased in 7 M SAMP8, IL-1β, IL-6 and iNOS decreased while TGF-β increased after IBM-BMT by RT-PCR. Moreover, oxidative stress-related heme oxygenase-1 (HO-1) increased in 7 M 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-1β, IL-6, iNOS and HO-1 are a result of the development of donor-derived BMCs.

Section snippets

Acknowledgments

The author thanks Mr. Hilary Eastwick-Field and Ms. K. Ando for their help in the preparation of the manuscript. These studies were mainly supported by the 21st Century Center of Excellence (COE) program of the Ministry of Education, Culture, Sports, Science and Technology. Supported also by a grant from Haiteku Research Center of the Ministry of Education, Health and Labor Sciences Research Grants, a grant from the Science Frontier program of the Ministry of Education, Culture, Sports, Science

References (42)

  • A.R. Simard et al.

    Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease

    Neuron

    (2006)
  • F.X. Sureda et al.

    Changes in oxidative stress parameters and neurodegeneration markers in the brain of the senescence-accelerated mice SAMP-8

    Exp. Gerontol.

    (2006)
  • R. Tenhunen et al.

    Microsomal heme oxygenase. Characterization of the enzyme

    J. Biol. Chem.

    (1969)
  • K.K. Tha et al.

    Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8

    Brain Res.

    (2000)
  • J. Wegiel et al.

    Cells of monocyte/microglial lineage are involved in both microvessel amyloidosis and fibrillar plaque formation in APPsw tg mice

    Brain Res.

    (2004)
  • H. Yagi et al.

    Age-related deterioration of ability of acquisition in memory and learning in senescence accelerated mouse: SAM-P/8 as an animal model of disturbances in recent memory

    Brain Res.

    (1988)
  • N.G. Abraham et al.

    Pharmacological and clinical aspects of heme oxygenase

    Pharmacol. Rev.

    (2008)
  • N.G. Abraham et al.

    Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity

    Proc. Natl. Acad. Sci. U.S.A.

    (1995)
  • N.G. Abraham et al.

    Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes

    Am. J. Physiol Heart Circ. Physiol.

    (2004)
  • J.C. Anthony et al.

    Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: the Cache County study

    Neurology

    (2000)
  • L.A. Applegate et al.

    Induction of heme oxygenase: a general response to oxidant stress in cultured mammalian cells

    Cancer Res.

    (1991)
  • Cited by (0)

    View full text