title: Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.
abstract: Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.
authors.affiliation: Department of Pathology, Aichi Human Service Center, Institute for Developmental Research, 713-8 Kamiya, Kasugai, Aichi, 480-0392, Japan.|Japan Society for the Promotion of Science, 5-3-1 Koujimachi, Chiyoda, Tokyo, 102-0083, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Hasegawa-Ishii
authors.affiliation: First Department of Internal Medicine, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Geriatrics, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Umegaki
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.affiliation: Department of Pathology, Aichi Human Service Center, Institute for Developmental Research, 713-8 Kamiya, Kasugai, Aichi, 480-0392, Japan. ats7@inst-hsc.jp.|Department of Pathology and Laboratory Medicine, Central Hospital, Aichi Human Service Center, 713-8 Kamiya, Kasugai, Aichi, 480-0392, Japan. ats7@inst-hsc.jp.
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
mesh_terms: D000375:Aging; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D002831:Choroid Plexus / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004805:Ependyma / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D016207:Cytokines
keywords: Astrocyte; Bone marrow; Choroid plexus; Cytokine; Ependyma; Median eminence; Tanycyte