Aarhus University Seal / Aarhus Universitets segl

Jens Randel Nyengaard

Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement. / Almgren, Malin; Persson, Ann-Sophie; Fenghua, Chen; Witgen, Brent M; Schalling, Martin; Nyengaard, Jens R; Lavebratt, Catharina.

In: The Hippocampus, Vol. 17, No. 4, 2007, p. 292-304.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Almgren, Malin ; Persson, Ann-Sophie ; Fenghua, Chen ; Witgen, Brent M ; Schalling, Martin ; Nyengaard, Jens R ; Lavebratt, Catharina. / Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement. In: The Hippocampus. 2007 ; Vol. 17, No. 4. pp. 292-304.

Bibtex

@article{81099a90d64511dcbc43000ea68e967b,
title = "Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement.",
abstract = "The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker-like voltage-gated potassium channel Kv1.1 brain, which results in a malfunctioning protein. A key question in elucidating the mechanism behind the unique brain overgrowth is whether it is caused by an increase in cell number. By applying stereological techniques, we found that the number of both neurons and astrocytes, as well as structure volume, was increased approximately two-fold within dentate gyrus (DG), CA2/3, and hilus of 12-week-old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth and the second week of life. To investigate the hyperplasia, cell proliferation was studied within the subgranular zone of the DG using BrdU and Ki67. There was a three-fold increase in proliferation in mceph/mceph mice compared to wild type mice at an age before onset of epileptic symptoms (3 weeks), and these new mceph/mceph neurons showed increased migration and had a 6-week survival rate as the new neurons in wild type DG. Also when seizures were frequent in mceph/mceph (9 weeks old), the proliferation rate was three-fold higher than in wild type. The number of TUNEL-positive cells in hippocampus was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks of age. This phenotype is a result, at least in DG, from increased proliferation, neurogenesis, and enhanced general hippocampal cell survival. Udgivelsesdato: 2007-null",
keywords = "Animals, Animals, Newborn, Bromodeoxyuridine, Cell Movement, Cell Proliferation, Cell Survival, Hippocampus, In Situ Nick-End Labeling, Ki-67 Antigen, Kv1.1 Potassium Channel, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Mutant Strains, Neurons, Stereotaxic Techniques",
author = "Malin Almgren and Ann-Sophie Persson and Chen Fenghua and Witgen, {Brent M} and Martin Schalling and Nyengaard, {Jens R} and Catharina Lavebratt",
year = "2007",
doi = "10.1002/hipo.20268",
language = "English",
volume = "17",
pages = "292--304",
journal = "The Hippocampus",
issn = "1050-9631",
publisher = "JohnWiley & Sons, Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement.

AU - Almgren, Malin

AU - Persson, Ann-Sophie

AU - Fenghua, Chen

AU - Witgen, Brent M

AU - Schalling, Martin

AU - Nyengaard, Jens R

AU - Lavebratt, Catharina

PY - 2007

Y1 - 2007

N2 - The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker-like voltage-gated potassium channel Kv1.1 brain, which results in a malfunctioning protein. A key question in elucidating the mechanism behind the unique brain overgrowth is whether it is caused by an increase in cell number. By applying stereological techniques, we found that the number of both neurons and astrocytes, as well as structure volume, was increased approximately two-fold within dentate gyrus (DG), CA2/3, and hilus of 12-week-old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth and the second week of life. To investigate the hyperplasia, cell proliferation was studied within the subgranular zone of the DG using BrdU and Ki67. There was a three-fold increase in proliferation in mceph/mceph mice compared to wild type mice at an age before onset of epileptic symptoms (3 weeks), and these new mceph/mceph neurons showed increased migration and had a 6-week survival rate as the new neurons in wild type DG. Also when seizures were frequent in mceph/mceph (9 weeks old), the proliferation rate was three-fold higher than in wild type. The number of TUNEL-positive cells in hippocampus was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks of age. This phenotype is a result, at least in DG, from increased proliferation, neurogenesis, and enhanced general hippocampal cell survival. Udgivelsesdato: 2007-null

AB - The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker-like voltage-gated potassium channel Kv1.1 brain, which results in a malfunctioning protein. A key question in elucidating the mechanism behind the unique brain overgrowth is whether it is caused by an increase in cell number. By applying stereological techniques, we found that the number of both neurons and astrocytes, as well as structure volume, was increased approximately two-fold within dentate gyrus (DG), CA2/3, and hilus of 12-week-old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth and the second week of life. To investigate the hyperplasia, cell proliferation was studied within the subgranular zone of the DG using BrdU and Ki67. There was a three-fold increase in proliferation in mceph/mceph mice compared to wild type mice at an age before onset of epileptic symptoms (3 weeks), and these new mceph/mceph neurons showed increased migration and had a 6-week survival rate as the new neurons in wild type DG. Also when seizures were frequent in mceph/mceph (9 weeks old), the proliferation rate was three-fold higher than in wild type. The number of TUNEL-positive cells in hippocampus was lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks of age. This phenotype is a result, at least in DG, from increased proliferation, neurogenesis, and enhanced general hippocampal cell survival. Udgivelsesdato: 2007-null

KW - Animals

KW - Animals, Newborn

KW - Bromodeoxyuridine

KW - Cell Movement

KW - Cell Proliferation

KW - Cell Survival

KW - Hippocampus

KW - In Situ Nick-End Labeling

KW - Ki-67 Antigen

KW - Kv1.1 Potassium Channel

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - Mice, Mutant Strains

KW - Neurons

KW - Stereotaxic Techniques

U2 - 10.1002/hipo.20268

DO - 10.1002/hipo.20268

M3 - Journal article

C2 - 17315199

VL - 17

SP - 292

EP - 304

JO - The Hippocampus

JF - The Hippocampus

SN - 1050-9631

IS - 4

ER -