Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients.
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Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients. / Fahrner, Alexander; Kann, Gunda; Flubacher, Armin; Heinrich, Christophe; Freiman, Thomas M; Zentner, Josef; Frotscher, Michael; Haas, Carola A.
In: EXP NEUROL, Vol. 203, No. 2, 2, 2007, p. 320-332.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients.
AU - Fahrner, Alexander
AU - Kann, Gunda
AU - Flubacher, Armin
AU - Heinrich, Christophe
AU - Freiman, Thomas M
AU - Zentner, Josef
AU - Frotscher, Michael
AU - Haas, Carola A
PY - 2007
Y1 - 2007
N2 - Granule cell dispersion (GCD) in the dentate gyrus is a frequent feature of Ammon's horn sclerosis (AHS) which is often associated with temporal lobe epilepsy (TLE). It has been hypothesized that GCD may be caused by an abnormal migration of newly born granule cells. To test this hypothesis, we used markers of proliferation and neurogenesis and immunocytochemical methods as well as quantitative Western blot and real-time RT-PCR analyses in surgically resected hippocampi from TLE patients and controls. Below the age of 1 year, Ki-67-immunopositive nuclei were detected in the subgranular zone of the dentate gyrus, but not in the dentate of TLE patients independent of age. The expression of the proliferation marker minichromosome maintenance protein 2 (mcm2) and of doublecortin (DCX) decreased significantly with age in controls and in TLE patients, but the expression of both proteins was independent of the degree of AHS and GCD. Quantitative real-time RT-PCR confirmed these findings at the level of gene expression. In contrast, immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin as well as Golgi staining revealed a radially aligned glial network in the region of GCD. GFAP-positive fiber length significantly increased with the severity of GCD. These results indicate that epileptic activity does not stimulate neurogenesis in the human dentate gyrus and that GCD probably does not result from a malpositioning of newly generated granule cells, but rather from an abnormal migration of mature granule cells along a radial glial scaffold.
AB - Granule cell dispersion (GCD) in the dentate gyrus is a frequent feature of Ammon's horn sclerosis (AHS) which is often associated with temporal lobe epilepsy (TLE). It has been hypothesized that GCD may be caused by an abnormal migration of newly born granule cells. To test this hypothesis, we used markers of proliferation and neurogenesis and immunocytochemical methods as well as quantitative Western blot and real-time RT-PCR analyses in surgically resected hippocampi from TLE patients and controls. Below the age of 1 year, Ki-67-immunopositive nuclei were detected in the subgranular zone of the dentate gyrus, but not in the dentate of TLE patients independent of age. The expression of the proliferation marker minichromosome maintenance protein 2 (mcm2) and of doublecortin (DCX) decreased significantly with age in controls and in TLE patients, but the expression of both proteins was independent of the degree of AHS and GCD. Quantitative real-time RT-PCR confirmed these findings at the level of gene expression. In contrast, immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin as well as Golgi staining revealed a radially aligned glial network in the region of GCD. GFAP-positive fiber length significantly increased with the severity of GCD. These results indicate that epileptic activity does not stimulate neurogenesis in the human dentate gyrus and that GCD probably does not result from a malpositioning of newly generated granule cells, but rather from an abnormal migration of mature granule cells along a radial glial scaffold.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Child
KW - Immunohistochemistry
KW - Infant
KW - development
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Nucleus metabolism
KW - Neurons physiology
KW - Glial Fibrillary Acidic Protein metabolism
KW - Blotting, Western
KW - Brain Neoplasms pathology
KW - Cytoplasmic Granules pathology
KW - Dentate Gyrus growth
KW - Epilepsy, Temporal Lobe pathology
KW - Glioblastoma pathology
KW - Hippocampus growth
KW - Ki-67 Antigen immunology
KW - Microtubule-Associated Proteins biosynthesis
KW - Mitosis physiology
KW - Neuroglia physiology
KW - Neuropeptides biosynthesis
KW - Vimentin metabolism
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Middle Aged
KW - Adolescent
KW - Child
KW - Immunohistochemistry
KW - Infant
KW - development
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Nucleus metabolism
KW - Neurons physiology
KW - Glial Fibrillary Acidic Protein metabolism
KW - Blotting, Western
KW - Brain Neoplasms pathology
KW - Cytoplasmic Granules pathology
KW - Dentate Gyrus growth
KW - Epilepsy, Temporal Lobe pathology
KW - Glioblastoma pathology
KW - Hippocampus growth
KW - Ki-67 Antigen immunology
KW - Microtubule-Associated Proteins biosynthesis
KW - Mitosis physiology
KW - Neuroglia physiology
KW - Neuropeptides biosynthesis
KW - Vimentin metabolism
M3 - SCORING: Zeitschriftenaufsatz
VL - 203
SP - 320
EP - 332
JO - EXP NEUROL
JF - EXP NEUROL
SN - 0014-4886
IS - 2
M1 - 2
ER -