Differential effect of lithium on cell number in the hippocampus and prefrontal cortex in adult mice: a stereological study
Objectives Neuroimaging studies have revealed lithium‐related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium‐treated subjects. Rodents treated...
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| Published in | Bipolar disorders Vol. 18; no. 1; pp. 41 - 51 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Denmark
Blackwell Publishing Ltd
01.02.2016
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1398-5647 1399-5618 1399-5618 |
| DOI | 10.1111/bdi.12364 |
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| Abstract | Objectives
Neuroimaging studies have revealed lithium‐related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium‐treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered.
Methods
Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex.
Results
Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium.
Conclusions
Both neuronal and glial cells accounted for lithium‐induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. |
|---|---|
| AbstractList | Objectives
Neuroimaging studies have revealed lithium‐related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium‐treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered.
Methods
Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex.
Results
Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium.
Conclusions
Both neuronal and glial cells accounted for lithium‐induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered.OBJECTIVESNeuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered.Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex.METHODSUsing stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex.Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium.RESULTSLithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium.Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus.CONCLUSIONSBoth neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. Objectives Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered. Methods Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex. Results Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium. Conclusions Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered. Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex. Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium. Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. |
| Author | Uylings, Harry BM Stockmeier, Craig A Clarke, Gerard van de Werd, Henri JJM Mahajan, Gouri Yuan, Peter Manji, Husseini K Rajkowska, Grazyna Licht, Camilla MM |
| AuthorAffiliation | 1 Dept. Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA 3 Dept. Anatomy & Neuroscience, VU University Medical Center, Amsterdam, the Netherlands 6 Janssen Research and Development LLC of Johnson & Johnson, Titusville, NJ, USA 4 Dept. Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, the Netherlands 2 Department of Psychiatry and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland 5 Laboratory of Molecular Pathophysiology and Experimental Therapeutics, NIMH, NIH, Bethesda, MD, USA |
| AuthorAffiliation_xml | – name: 4 Dept. Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, the Netherlands – name: 1 Dept. Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA – name: 2 Department of Psychiatry and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland – name: 5 Laboratory of Molecular Pathophysiology and Experimental Therapeutics, NIMH, NIH, Bethesda, MD, USA – name: 3 Dept. Anatomy & Neuroscience, VU University Medical Center, Amsterdam, the Netherlands – name: 6 Janssen Research and Development LLC of Johnson & Johnson, Titusville, NJ, USA |
| Author_xml | – sequence: 1 givenname: Grazyna surname: Rajkowska fullname: Rajkowska, Grazyna email: Corresponding author:Grazyna Rajkowska, Ph.D.Department of Psychiatry and Human BehaviorUniversity of Mississippi Medical Center2500 North State StreetJackson, MS 39216USAFax: 601-984-5899, grajkowska@umc.edu organization: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, MS, Jackson, USA – sequence: 2 givenname: Gerard surname: Clarke fullname: Clarke, Gerard organization: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA – sequence: 3 givenname: Gouri surname: Mahajan fullname: Mahajan, Gouri organization: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, MS, Jackson, USA – sequence: 4 givenname: Camilla MM surname: Licht fullname: Licht, Camilla MM organization: Department of Anatomy and Neuroscience, VU University Medical Center – sequence: 5 givenname: Henri JJM surname: van de Werd fullname: van de Werd, Henri JJM organization: Department of Anatomy and Neuroscience, VU University Medical Center – sequence: 6 givenname: Peter surname: Yuan fullname: Yuan, Peter organization: Laboratory of Molecular Pathophysiology and Experimental Therapeutics, National Institute of Mental Health, National Institutes of Health, MD, Bethesda, USA – sequence: 7 givenname: Craig A surname: Stockmeier fullname: Stockmeier, Craig A organization: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, MS, Jackson, USA – sequence: 8 givenname: Husseini K surname: Manji fullname: Manji, Husseini K organization: Laboratory of Molecular Pathophysiology and Experimental Therapeutics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA – sequence: 9 givenname: Harry BM surname: Uylings fullname: Uylings, Harry BM organization: Department of Anatomy and Neuroscience, VU University Medical Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26842627$$D View this record in MEDLINE/PubMed |
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| Keywords | adult neurogenesis lithium bipolar disorder stereology astrocytes glia neurons |
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Neuroimaging studies have revealed lithium‐related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem... Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human... Objectives Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem... |
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| SubjectTerms | adult neurogenesis Animals astrocytes Astrocytes - drug effects bipolar disorder Bipolar Disorder - pathology Cell Count Dentate Gyrus - cytology Dentate Gyrus - drug effects Dentate Gyrus - pathology glia Hippocampus - cytology Hippocampus - drug effects Hippocampus - pathology lithium Lithium Compounds - pharmacology Male Mice Mice, Inbred C57BL Neuroglia - drug effects neurons Neurons - drug effects Organ Size - drug effects Prefrontal Cortex - cytology Prefrontal Cortex - drug effects Prefrontal Cortex - pathology stereology |
| Title | Differential effect of lithium on cell number in the hippocampus and prefrontal cortex in adult mice: a stereological study |
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