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Jens Randel Nyengaard

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

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  • Malin Almgren, Denmark
  • Ann-Sophie Persson, Denmark
  • Chen Fenghua
  • Brent M Witgen, Denmark
  • Martin Schalling, Denmark
  • Jens R Nyengaard
  • Catharina Lavebratt, Denmark
  • Stereological Research Laboratory
  • Institute of Clinical Medicine
  • The Department of Pathology - ÅKH
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
Original languageEnglish
JournalThe Hippocampus
Pages (from-to)292-304
Number of pages12
Publication statusPublished - 2007

    Research areas

  • 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

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