title: Characterization of spinal cord glial cells in a model of hindlimb unloading in mice.
abstract: Exposure to microgravity has been shown to result in damaging alterations to skeletal muscle, bones, and inner organs. In this study, we investigated the effects of microgravity by using a hindlimb unloading model (HUM) in mice. The characteristics of the lumbar spinal cords of HUM mice 30 days after hindlimb unloading were examined. Morphometric analysis showed reductions of the total area, gray matter, and white matter by 17%, 20%, and 12%, respectively. Myelinated fibers in the white matter showed prominent myelin destruction. Analysis of the number of glial fibrillary acidic protein (GFAP+)/S100 calcium-binding protein B (S100B-), GFAP+/S100B+, and GFAP-/S100B+ astrocytes in the ventral horn (VH), central channel area (CC), dorsal root entry zone (DREZ), main corticospinal tract (CST), and ventral funiculi (VF) showed that the number of GFAP+/S100B- astrocytes was increased in the DREZ and CST of HUM mice. Additionally, GFAP+/S100B+ cell numbers were significantly decreased in the VH and CST but did not differ in the CC or DREZ of HUM mice, as compared with the control. The numbers of GFAP-/S100B+ cells were significantly reduced only in the VH of HUM mice. Moreover, the number of ionized calcium-binding adaptor molecule 1 (Iba1+) microglia cells was significantly increased in the CC and DREZ of HUM mice. In control mice, homeobox protein HoxB8 (HoxB8+) cells were found only in the CC; in contrast, HoxB8+ cells were observed in all studied areas in HUM mice, with the greatest number found in the CC. Genome-wide transcriptome analysis of the lumbar spinal cords of HUM mice showed decreased expression of genes encoding myelin, extracellular matrix, cytoskeleton, and cell adhesion proteins. Real-time polymerase chain reaction (PCR) confirmed reductions in the expression of mpz, pmp2, pmp22, and prx genes, which are involved in myelination, as well as decreases in the levels of genes encoding extracellular matrix molecules, including glycoproteins (matrix gla protein (MGP), osteoglycin (OGN), microfibrillar associated protein 5 (MFAP), and collagen, type IV, alpha 1 (COL4A)), proteoglycans (perlecan (heparan sulfate proteoglycan) (HSPG)), and metalloproteinases (lysyl oxidase (LOX)). Thus, our results showed that hindlimb unloading caused decreases in gray and white matter areas, changes in gene expression, alterations in myelination, and phenotypic modifications in glial cells in the lumbar spinal cords of mice.
authors.affiliation: Kazan State Medical University, Kazan, Russia; Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: Y A
authors.initials: YA
authors.lastname: Chelyshev
authors.affiliation: Kazan State Medical University, Kazan, Russia. Electronic address: yanakazmedhist1@rambler.ru.
authors.forename: Y O
authors.initials: YO
authors.lastname: Muhamedshina
authors.affiliation: Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: T V
authors.initials: TV
authors.lastname: Povysheva
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia.
authors.forename: G F
authors.initials: GF
authors.lastname: Shaymardanova
authors.affiliation: Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Nigmetzyanova
authors.affiliation: Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Tiapkina
authors.affiliation: Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: N I
authors.initials: NI
authors.lastname: Bondarenko
authors.affiliation: Kazan State Medical University, Kazan, Russia; Kazan Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia; Kazan (Volga Region) Federal University, Kazan, Russia.
authors.forename: E E
authors.initials: EE
authors.lastname: Nikolskiy
authors.affiliation: Kazan State Medical University, Kazan, Russia.
authors.forename: R R
authors.initials: RR
authors.lastname: Islamov
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005904:Glial Fibrillary Acidic Protein; D066128:Gray Matter / Q000378:metabolism / Q000648:ultrastructure; D019417:Hindlimb Suspension; D018398:Homeodomain Proteins / Q000378:metabolism; D008159:Lumbar Vertebrae; D008297:Male; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D060888:Real-Time Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000648:ultrastructure; D066127:White Matter / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; C528900:glial fibrillary astrocytic protein, mouse
keywords: glia; hindlimb unloading model; myelin; spinal cord