Abstract
We examined the expression of galectin-1, an endogenous lectin with one carbohydrate-binding domain, in the adult mouse hippocampus after systemic kainate administration. We found that the expression of galectin-1 was remarkably increased in activated astrocytes of the CA3 subregion and dentate gyrus of the hippocampus, and in nestin-positive neural progenitors in the dentate gyrus. Quantitative reverse transcription PCR (RT-PCR) analysis revealed that the galectin-1 mRNA level in hippocampus began to increase 1 day after kainate administration and that a 13-fold increase was attained within 3 days. Western blotting analysis confirmed that the level of galectin-1 protein increased to more than three-fold a week after the exposure. We showed that isolated astrocytes express and secrete galectin-1. To clarify the significance of the increased expression of galectin-1 in hippocampus, we compared the levels of hippocampal cell proliferation in galectin-1 knockout and wild-type mice after saline or kainate administration. The number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells detected in the subgranular zone (SGZ) of galectin-1 knockout mice decreased to 62% with saline, and to 52% with kainate, as compared with the number seen in the wild-type mice. Most of the BrdU-positive cells in SGZ expressed doublecortin and neuron-specific nuclear protein, indicating that they are immature neurons. We therefore concluded that galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the hippocampus.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BrdU:
-
5-bromo-2′-deoxyuridine
- DCX:
-
doublecortin
- GCL:
-
granule cell layer
- GFAP:
-
glial fibrillary acidic protein
- IHC:
-
immunohistochemistry
- NeuN:
-
neuron-specific nuclear protein
- PSA-NCAM:
-
polysialylated neural cell adhesion molecule
- SGZ:
-
subgranular zone
- SVZ:
-
subventricular zone
References
Morrison JH, Hof PR . Life and death of neurons in the aging brain. Science 1997; 278: 412–419.
Meltzer LA, Yabaluri R, Deisseroth K . A role for circuit homeostasis in adult neurogenesis. Trends Neurosci 2005; 28: 653–660.
Zhao C, Deng W, Gage FH . Mechanisms and functional implications of adult neurogenesis. Cell 2008; 132: 645–660.
Liu J, Solway K, Messing RO, Sharp FR . Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 1998; 18: 7768–7778.
Gray WP, Sundstrom LE . Kainic acid increases the proliferation of granule cell progenitors in the dentate gyrus of the adult rat. Brain Res 1998; 790: 52–59.
Herdegen T, Leah JD . Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 1998; 28: 370–490.
Nakabeppu Y, Ryder K, Nathans D . DNA binding activities of three murine Jun proteins: stimulation by Fos. Cell 1988; 55: 907–915.
Nakabeppu Y, Nathans D . A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity. Cell 1991; 64: 751–759.
Nakabeppu Y, Oda S, Sekiguchi M . Proliferative activation of quiescent Rat-1A cells by ΔFosB. Mol Cell Biol 1993; 13: 4157–4166.
Oda S, Nishida J, Nakabeppu Y, Sekiguchi M . Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state. Oncogene 1995; 10: 1343–1351.
Nishioka T, Sakumi K, Miura T, Tahara K, Horie H, Kadoya T et al. FosB gene products trigger cell proliferation and morphological alteration with an increased expression of a novel processed form of galectin-1 in the rat 3Y1 embryo cell line. J Biochem 2002; 131: 653–661.
Tahara K, Tsuchimoto D, Tominaga Y, Asoh S, Ohta S, Kitagawa M et al. FosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line. Cell Death Differ 2003; 10: 496–507.
Kurushima H, Ohno M, Miura T, Nakamura TY, Horie H, Kadoya T et al. Selective induction of ΔFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of ΔFosB and galectin-1 in neuroprotection and neurogenesis. Cell Death Differ 2005; 12: 1078–1096.
Miura T, Takahashi M, Horie H, Kurushima H, Tsuchimoto D, Sakumi K et al. Galectin-1beta, a natural monomeric form of galectin-1 lacking its six amino-terminal residues promotes axonal regeneration but not cell death. Cell Death Differ 2004; 11: 1076–1083.
Miura T, Ohnishi Y, Kurushima H, Horie H, Kadoya T, Nakabeppu Y . Regulation of the neuronal fate by DeltaFosB and its downstream target, galectin-1. Curr Drug Targets 2005; 6: 437–444.
Barondes SH, Cooper DN, Gitt MA, Leffler H . Galectins. Structure and function of a large family of animal lectins. J Biol Chem 1994; 269: 20807–20810.
Hsu DK, Liu FT . Regulation of cellular homeostasis by galectins. Glycoconj J 2004; 19: 507–515.
Scott K, Weinberg C . Galectin-1: a bifunctional regulator of cellular proliferation. Glycoconj J 2004; 19: 467–477.
Puche AC, Poirier F, Hair M, Bartlett PF, Key B . Role of galectin-1 in the developing mouse olfactory system. Dev Biol 1996; 179: 274–287.
Horie H, Inagaki Y, Sohma Y, Nozawa R, Okawa K, Hasegawa M et al. Galectin-1 regulates initial axonal growth in peripheral nerves after axotomy. J Neurosci 1999; 19: 9964–9974.
Kajitani K, Yamaguchi H, Dan Y, Furuichi M, Kang D, Nakabeppu Y . MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity. J Neurosci 2006; 26: 1688–1698.
Royle SJ, Collins FC, Rupniak HT, Barnes JC, Anderson R . Behavioural analysis and susceptibility to CNS injury of four inbred strains of mice. Brain Res 1999; 816: 337–349.
Sakaguchi M, Shingo T, Shimazaki T, Okano HJ, Shiwa M, Ishibashi S et al. A carbohydrate-binding protein, galectin-1, promotes proliferation of adult neural stem cells. Proc Natl Acad Sci USA 2006; 103: 7112–7117.
Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH . Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 1997; 17: 3727–3738.
Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 2001; 98: 4710–4715.
Jin K, Galvan V, Xie L, Mao XO, Gorostiza OF, Bredesen DE et al. Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) mice. Proc Natl Acad Sci USA 2004; 101: 13363–13367.
Georgiadis V, Stewart HJ, Pollard HJ, Tavsanoglu Y, Prasad R, Horwood J et al. Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration. Dev Dyn 2007; 236: 1014–1024.
Song H, Stevens CF, Gage FH . Astroglia induce neurogenesis from adult neural stem cells. Nature 2002; 417: 39–44.
Kempermann G, Jessberger S, Steiner B, Kronenberg G . Milestones of neuronal development in the adult hippocampus. Trends Neurosci 2004; 27: 447–452.
Sakaguchi M, Imaizumi Y, Okano H . Expression and function of galectin-1 in adult neural stem cells. Cell Mol Life Sci 2007; 64: 1254–1258.
Sasaki T, Hirabayashi J, Manya H, Kasai K, Endo T . Galectin-1 induces astrocyte differentiation, which leads to production of brain-derived neurotrophic factor. Glycobiology 2004; 14: 357–363.
Lee J, Duan W, Mattson MP . Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 2002; 82: 1367–1375.
Horie H, Kadoya T, Hikawa N, Sango K, Inoue H, Takeshita K et al. Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy. J Neurosci 2004; 24: 1873–1880.
Poirier F, Robertson EJ . Normal development of mice carrying a null mutation in the gene encoding the L14 S-type lectin. Development 1993; 119: 1229–1236.
Yang DD, Kuan CY, Whitmarsh AJ, Rincon M, Zheng TS, Davis RJ et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 1997; 389: 865–870.
Franklin KB, Paxinos G . The Mouse Brain in Stereotaxic Coordinates. Academic Press: New York, 2001.
Kempermann G, Kuhn HG, Gage FH . Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 1998; 18: 3206–3212.
Tsuchimoto D, Sakai Y, Sakumi K, Nishioka K, Sasaki M, Fujiwara T et al. Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen. Nucleic Acids Res 2001; 29: 2349–2360.
Lyons SA, Kettenmann H . Oligodendrocytes and microglia are selectively vulnerable to combined hypoxia and hypoglycemia injury in vitro. J Cereb Blood Flow Metab 1998; 18: 521–530.
Acknowledgements
We are grateful to Dr. Kanba for providing us with the opportunity to conduct this study, and Dr. W Campbell for useful comments on this manuscript. We thank S Kitamura and A Matsuyama for their technical expertise. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Japan Society for the Promotion of Science (to Y Nakabeppu); the 21st Century Centers of Excellence Program of MEXT (to Kyushu University); Kyushu University Interdisciplinary Programs in Education and Projects in Research Development (to K Kajitani); and Ligue Contre le Cancer, Comite de Paris, and Association Contre le Cancer (to F Poirier).
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by P Vandenabeele
Supplementary Information accompanies the paper on Cell Death and Differentiation website (http://www.nature.com/cdd)
Rights and permissions
About this article
Cite this article
Kajitani, K., Nomaru, H., Ifuku, M. et al. Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus. Cell Death Differ 16, 417–427 (2009). https://doi.org/10.1038/cdd.2008.162
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/cdd.2008.162
Keywords
This article is cited by
-
Neuroprotective Effect of Exogenous Galectin-1 in Status Epilepticus
Molecular Neurobiology (2022)
-
Serum galectin-3, but not galectin-1, levels are elevated in schizophrenia: implications for the role of inflammation
Psychopharmacology (2017)
-
Complexity of Stomach–Brain Interaction Induced by Molecular Hydrogen in Parkinson’s Disease Model Mice
Neurochemical Research (2017)
-
ConBr, A Lectin Purified from the Seeds of Canavalia brasiliensis, Protects Against Ischemia in Organotypic Culture of Rat Hippocampus: Potential Implication of Voltage-Gated Calcium Channels
Neurochemical Research (2017)
-
Modulation of the Mesenchymal Stem Cell Secretome Using Computer-Controlled Bioreactors: Impact on Neuronal Cell Proliferation, Survival and Differentiation
Scientific Reports (2016)
