title: Chronic Lithium Treatment Enhances the Number of Quiescent Neural Progenitors but Not the Number of DCX-Positive Immature Neurons.
abstract: BACKGROUND
  The term adult neurogenesis constitutes a series of developmental steps including the birth, survival, differentiation, maturation, and even death of newborn progenitor cells within neurogenic niches. Within the hippocampus progenitors reside in the neurogenic niche of the subgranular zone in the dentate gyrus subfield. At the different stages, designated type-I, type-IIa, type-IIb, type-III, and granule cell neurons, the cells express a series of markers enabling their identification and visualization. Lithium has been shown to increase hippocampal cell proliferation in the subgranular zone of the hippocampal dentate gyrus subfield of adult rodents and to stimulate the proliferation of hippocampal progenitor cells in vitro, but data regarding lithium's ability to increase neuronal differentiation and survival is equivocal.
  
  
  METHODS
  To clarify the effect of lithium on adult hippocampal neurogenesis, we identified the effect of chronic lithium treatment on distinct stages of hippocampal progenitor development using adult Nestin-green fluorescent protein transgenic mice and immunofluorescent techniques.
  
  
  RESULTS
  The present observations confirm that lithium targets the initial stages of progenitor development enhancing the turnover of quiescent neural progenitors/putative stem-cells, corroborating previous reports. However, the enhanced quiescent neural progenitor-turnover does not translate into an increased number of immature neurons. We also observed a steep decline in the number of type-III immature neurons with complex tertiary-dendrites, suggesting that lithium alters the morphological maturation of newborn neurons.
  
  
  CONCLUSIONS
  Our results do not corroborate previous reports of lithium-induced enhanced numbers of newly generated neurons.
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
authors: N
authors: N
authors: Kara
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
authors: S
authors: S
authors: Narayanan
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
authors: R H
authors: RH
authors: Belmaker
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
authors: H
authors: H
authors: Einat
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat).
authors: V A
authors: VA
authors: Vaidya
authors: Department of Clinical Biochemistry and Pharmacology (Ms Kara and Dr Agam), and Psychiatry Research Unit (Ms Kara and Drs Belmaker and Agam), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Mental Health Center, Beer-Sheva, Israel (Ms Kara and Dr Agam); Tel Aviv-Yaffo Academic College, Tel Aviv-Yaffo, Israel (Ms Kara and Dr Einat); Tata Institute of Fundamental Research, Mumbai, India (Ms Narayanan and Dr Vaidya); University of Minnesota, Minneapolis, Minnesota (Dr Einat). galila@bgu.ac.il vvaidya@tifr.res.in.
authors: G
authors: G
authors: Agam
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D000089662:Doublecortin Protein; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D018020:Lithium Compounds; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D018020:Lithium Compounds; C577485:Nes protein, mouse; D064231:Nestin; D049452:Green Fluorescent Proteins
keywords: Nestin-GFP transgenic mice; immature neurons; lithium; neurogenesis; quiescent neural progenitor cells
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