Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo

Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride...

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Veröffentlicht in:Journal of neurochemistry 2004-04, Vol.89 (2), p.324-336
Hauptverfasser: Kim, Jin Seuk, Chang, Mi‐Yoon, Yu, In Tag, Kim, Ju Hee, Lee, Sang‐Hun, Lee, Yong‐Sung, Son, Hyeon
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container_title Journal of neurochemistry
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creator Kim, Jin Seuk
Chang, Mi‐Yoon
Yu, In Tag
Kim, Ju Hee
Lee, Sang‐Hun
Lee, Yong‐Sung
Son, Hyeon
description Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1–3 mm) produced a significant increase in the number of bromodeoxyuridine (BrdU)‐positive cells in high‐density cultures, but did not increase clonal size in low‐density cultures. Lithium chloride at 1 mm (within the therapeutic range) also increased the number of cells double‐labeled with BrdU antibody and TuJ1 (a class III β‐tubulin antibody) in high‐density cultures and the number of TuJ1‐positive cells in a clone of low‐density cultures, whereas it decreased the number of glial fibrillary acidic protein‐positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindinD28k‐positive cells, and involved a phosphorylated extracellular signal‐regulated kinase and phosphorylated cyclic AMP response element‐binding protein‐dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindinD28k‐positive neuronal cell type.
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The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1–3 mm) produced a significant increase in the number of bromodeoxyuridine (BrdU)‐positive cells in high‐density cultures, but did not increase clonal size in low‐density cultures. Lithium chloride at 1 mm (within the therapeutic range) also increased the number of cells double‐labeled with BrdU antibody and TuJ1 (a class III β‐tubulin antibody) in high‐density cultures and the number of TuJ1‐positive cells in a clone of low‐density cultures, whereas it decreased the number of glial fibrillary acidic protein‐positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindinD28k‐positive cells, and involved a phosphorylated extracellular signal‐regulated kinase and phosphorylated cyclic AMP response element‐binding protein‐dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindinD28k‐positive neuronal cell type.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1046/j.1471-4159.2004.02329.x</identifier><identifier>PMID: 15056276</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; Antigens, Differentiation - biosynthesis ; Astrocytes - cytology ; Astrocytes - metabolism ; Biological and medical sciences ; Bromodeoxyuridine ; calbindin ; Calbindin 1 ; Calbindins ; Cell Count ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Cell differentiation, maturation, development, hematopoiesis ; Cell Division - drug effects ; Cell physiology ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein - metabolism ; dentate gyrus ; extracellular signal‐regulated kinase ; Fundamental and applied biological sciences. Psychology ; hippocampus ; Hippocampus - cytology ; Hippocampus - drug effects ; Hippocampus - physiology ; Immunohistochemistry ; Isolated neuron and nerve. Neuroglia ; lithium ; Lithium - pharmacology ; Male ; Microtubule-Associated Proteins - biosynthesis ; Mitogen-Activated Protein Kinases - metabolism ; Molecular and cellular biology ; neurogenesis ; Neurons - cytology ; Neurons - metabolism ; rat ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein G - biosynthesis ; Signal Transduction - drug effects ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - metabolism ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of neurochemistry, 2004-04, Vol.89 (2), p.324-336</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3959-d5c345b7d732aee070b64ac803974025f5425cc62436d47e7cc649e9c5b28d343</citedby><cites>FETCH-LOGICAL-c3959-d5c345b7d732aee070b64ac803974025f5425cc62436d47e7cc649e9c5b28d343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1471-4159.2004.02329.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1471-4159.2004.02329.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,1434,27926,27927,45576,45577,46411,46835</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=15620060$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15056276$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jin Seuk</creatorcontrib><creatorcontrib>Chang, Mi‐Yoon</creatorcontrib><creatorcontrib>Yu, In Tag</creatorcontrib><creatorcontrib>Kim, Ju Hee</creatorcontrib><creatorcontrib>Lee, Sang‐Hun</creatorcontrib><creatorcontrib>Lee, Yong‐Sung</creatorcontrib><creatorcontrib>Son, Hyeon</creatorcontrib><title>Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1–3 mm) produced a significant increase in the number of bromodeoxyuridine (BrdU)‐positive cells in high‐density cultures, but did not increase clonal size in low‐density cultures. Lithium chloride at 1 mm (within the therapeutic range) also increased the number of cells double‐labeled with BrdU antibody and TuJ1 (a class III β‐tubulin antibody) in high‐density cultures and the number of TuJ1‐positive cells in a clone of low‐density cultures, whereas it decreased the number of glial fibrillary acidic protein‐positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindinD28k‐positive cells, and involved a phosphorylated extracellular signal‐regulated kinase and phosphorylated cyclic AMP response element‐binding protein‐dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindinD28k‐positive neuronal cell type.</description><subject>Animals</subject><subject>Antigens, Differentiation - biosynthesis</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bromodeoxyuridine</subject><subject>calbindin</subject><subject>Calbindin 1</subject><subject>Calbindins</subject><subject>Cell Count</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell Division - drug effects</subject><subject>Cell physiology</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>dentate gyrus</subject><subject>extracellular signal‐regulated kinase</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>hippocampus</subject><subject>Hippocampus - cytology</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - physiology</subject><subject>Immunohistochemistry</subject><subject>Isolated neuron and nerve. Neuroglia</subject><subject>lithium</subject><subject>Lithium - pharmacology</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - biosynthesis</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Molecular and cellular biology</subject><subject>neurogenesis</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>rat</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>S100 Calcium Binding Protein G - biosynthesis</subject><subject>Signal Transduction - drug effects</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE2P0zAQhi0EYsvCX0C-wC3B324OHFC1fKmCC5wtx5lQV4kd7KS7_fc4tAKOnGaseWb86kEIU1JTItSbY02FppWgsqkZIaImjLOmfniENn8Gj9GGEMYqTgS7Qc9yPhJClVD0KbqhkkjFtNqg-72fD34ZcYYB3OxPMJyxDy6BzZBxgCXFYAfc-b6HBGH2dvYx4Njjg5-m6Ow4lfHKlTKl-AOCn2PCDoYh4zbOh3IOn_ycIrahuzxO8Tl60tshw4trvUXf3999232s9l8_fNq921eON7KpOum4kK3uNGcWgGjSKmHdlvBGC8JkLwWTzikmuOqEBl160UDjZMu2HRf8Fr2-3C3Rfi6QZzP6vGazAeKSjaZ62yjKCri9gC7FnBP0Zkp-tOlsKDGrdHM0q1uzujWrdPNbunkoqy-vfyztCN3fxavlAry6AjY7O_TJBufzP5wq9xQp3NsLd-8HOP93APP5y27t-C8YWJ8T</recordid><startdate>200404</startdate><enddate>200404</enddate><creator>Kim, Jin Seuk</creator><creator>Chang, Mi‐Yoon</creator><creator>Yu, In Tag</creator><creator>Kim, Ju Hee</creator><creator>Lee, Sang‐Hun</creator><creator>Lee, Yong‐Sung</creator><creator>Son, Hyeon</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200404</creationdate><title>Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo</title><author>Kim, Jin Seuk ; Chang, Mi‐Yoon ; Yu, In Tag ; Kim, Ju Hee ; Lee, Sang‐Hun ; Lee, Yong‐Sung ; Son, Hyeon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3959-d5c345b7d732aee070b64ac803974025f5425cc62436d47e7cc649e9c5b28d343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Antigens, Differentiation - biosynthesis</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bromodeoxyuridine</topic><topic>calbindin</topic><topic>Calbindin 1</topic><topic>Calbindins</topic><topic>Cell Count</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - physiology</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell Division - drug effects</topic><topic>Cell physiology</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>dentate gyrus</topic><topic>extracellular signal‐regulated kinase</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>hippocampus</topic><topic>Hippocampus - cytology</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - physiology</topic><topic>Immunohistochemistry</topic><topic>Isolated neuron and nerve. Neuroglia</topic><topic>lithium</topic><topic>Lithium - pharmacology</topic><topic>Male</topic><topic>Microtubule-Associated Proteins - biosynthesis</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Molecular and cellular biology</topic><topic>neurogenesis</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>rat</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>S100 Calcium Binding Protein G - biosynthesis</topic><topic>Signal Transduction - drug effects</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jin Seuk</creatorcontrib><creatorcontrib>Chang, Mi‐Yoon</creatorcontrib><creatorcontrib>Yu, In Tag</creatorcontrib><creatorcontrib>Kim, Ju Hee</creatorcontrib><creatorcontrib>Lee, Sang‐Hun</creatorcontrib><creatorcontrib>Lee, Yong‐Sung</creatorcontrib><creatorcontrib>Son, Hyeon</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jin Seuk</au><au>Chang, Mi‐Yoon</au><au>Yu, In Tag</au><au>Kim, Ju Hee</au><au>Lee, Sang‐Hun</au><au>Lee, Yong‐Sung</au><au>Son, Hyeon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>2004-04</date><risdate>2004</risdate><volume>89</volume><issue>2</issue><spage>324</spage><epage>336</epage><pages>324-336</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>Lithium has been demonstrated to increase neurogenesis in the dentate gyrus of rodent hippocampus. The present study was undertaken to investigate the effects of lithium on the proliferation and differentiation of rat neural progenitor cells in hippocampus both in vitro and in vivo. Lithium chloride (1–3 mm) produced a significant increase in the number of bromodeoxyuridine (BrdU)‐positive cells in high‐density cultures, but did not increase clonal size in low‐density cultures. Lithium chloride at 1 mm (within the therapeutic range) also increased the number of cells double‐labeled with BrdU antibody and TuJ1 (a class III β‐tubulin antibody) in high‐density cultures and the number of TuJ1‐positive cells in a clone of low‐density cultures, whereas it decreased the number of glial fibrillary acidic protein‐positive cells in both cultures. These results suggest that lithium selectively increased differentiation of neuronal progenitors. These actions of lithium appeared to enhance a neuronal subtype, calbindinD28k‐positive cells, and involved a phosphorylated extracellular signal‐regulated kinase and phosphorylated cyclic AMP response element‐binding protein‐dependent pathway both in vitro and in vivo. These findings suggest that lithium in therapeutic amounts may elicit its beneficial effects via facilitation of neural progenitor differentiation toward a calbindinD28k‐positive neuronal cell type.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15056276</pmid><doi>10.1046/j.1471-4159.2004.02329.x</doi><tpages>13</tpages></addata></record>
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subjects Animals
Antigens, Differentiation - biosynthesis
Astrocytes - cytology
Astrocytes - metabolism
Biological and medical sciences
Bromodeoxyuridine
calbindin
Calbindin 1
Calbindins
Cell Count
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell differentiation, maturation, development, hematopoiesis
Cell Division - drug effects
Cell physiology
Cells, Cultured
Cyclic AMP Response Element-Binding Protein - metabolism
dentate gyrus
extracellular signal‐regulated kinase
Fundamental and applied biological sciences. Psychology
hippocampus
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - physiology
Immunohistochemistry
Isolated neuron and nerve. Neuroglia
lithium
Lithium - pharmacology
Male
Microtubule-Associated Proteins - biosynthesis
Mitogen-Activated Protein Kinases - metabolism
Molecular and cellular biology
neurogenesis
Neurons - cytology
Neurons - metabolism
rat
Rats
Rats, Sprague-Dawley
S100 Calcium Binding Protein G - biosynthesis
Signal Transduction - drug effects
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Vertebrates: nervous system and sense organs
title Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo
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