The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice

A. Alpár, Uwe Ueberham, Martina K. Brückner, Thomas Arendt, Ulrich Gärtner

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The current study addresses the morphoregulatory effects of human amyloid precursor protein expression on neocortical pyramidal cells in vivo. For this purpose, a transgenic mouse line was used that expresses wild-type human amyloid precursor protein (APP) at levels similar to endogenous mouse APP [introduced by Lamb, B.T., Sisodia, S.S., Lawler, A.M., Slunt, H.H., Kitt, C.A., Kearns, W.G., Pearson, P.L., Price, D.L., Gearhart, J.D., 1993. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat. Genet. 5, 22-30]. This strain does not develop Alzheimer's disease-related pathology which allowed to study effects of APP or APP cleavage products but excluded the influence of amyloid deposits. Commissural projecting pyramidal neurons of layers II/III within the primary somatosensory cortex were retrogradely labelled by injection of biotinylated dextran amine into the corpus callosum. In transgenic mice, computer-aided morphometric analysis revealed an increase in the surface area of proximal and intermediate basal dendritic segments resulting from an enlarged diameter. On the other hand, the length of the same segments was reduced. Both basal and apical dendrites were characterized by a higher dendritic density within the proximal and intermediate fields. Although the total spatial extension of basal and apical dendrites remained unchanged, a moderate withdrawal of arbors is suggested. The results implicate a physiological function for APP in regulatory mechanisms of neuronal morphogenesis.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalInternational Journal of Developmental Neuroscience
Volume24
Issue number2-3
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Amyloid beta-Protein Precursor
Pyramidal Cells
Transgenic Mice
Phenotype
Dendrites
Viverridae
Somatosensory Cortex
Corpus Callosum
Amyloid Plaques
Morphogenesis
Alzheimer Disease
Pathology
Injections
Genes

Keywords

  • Alzheimer's disease
  • Dendritic morphology
  • Human amyloid precursor protein

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice. / Alpár, A.; Ueberham, Uwe; Brückner, Martina K.; Arendt, Thomas; Gärtner, Ulrich.

In: International Journal of Developmental Neuroscience, Vol. 24, No. 2-3, 04.2006, p. 133-140.

Research output: Contribution to journalArticle

@article{2471317fa3e3411fb4a6310b1bf0e159,
title = "The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice",
abstract = "The current study addresses the morphoregulatory effects of human amyloid precursor protein expression on neocortical pyramidal cells in vivo. For this purpose, a transgenic mouse line was used that expresses wild-type human amyloid precursor protein (APP) at levels similar to endogenous mouse APP [introduced by Lamb, B.T., Sisodia, S.S., Lawler, A.M., Slunt, H.H., Kitt, C.A., Kearns, W.G., Pearson, P.L., Price, D.L., Gearhart, J.D., 1993. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat. Genet. 5, 22-30]. This strain does not develop Alzheimer's disease-related pathology which allowed to study effects of APP or APP cleavage products but excluded the influence of amyloid deposits. Commissural projecting pyramidal neurons of layers II/III within the primary somatosensory cortex were retrogradely labelled by injection of biotinylated dextran amine into the corpus callosum. In transgenic mice, computer-aided morphometric analysis revealed an increase in the surface area of proximal and intermediate basal dendritic segments resulting from an enlarged diameter. On the other hand, the length of the same segments was reduced. Both basal and apical dendrites were characterized by a higher dendritic density within the proximal and intermediate fields. Although the total spatial extension of basal and apical dendrites remained unchanged, a moderate withdrawal of arbors is suggested. The results implicate a physiological function for APP in regulatory mechanisms of neuronal morphogenesis.",
keywords = "Alzheimer's disease, Dendritic morphology, Human amyloid precursor protein",
author = "A. Alp{\'a}r and Uwe Ueberham and Br{\"u}ckner, {Martina K.} and Thomas Arendt and Ulrich G{\"a}rtner",
year = "2006",
month = "4",
doi = "10.1016/j.ijdevneu.2005.11.008",
language = "English",
volume = "24",
pages = "133--140",
journal = "International Journal of Developmental Neuroscience",
issn = "0736-5748",
publisher = "Elsevier Limited",
number = "2-3",

}

TY - JOUR

T1 - The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice

AU - Alpár, A.

AU - Ueberham, Uwe

AU - Brückner, Martina K.

AU - Arendt, Thomas

AU - Gärtner, Ulrich

PY - 2006/4

Y1 - 2006/4

N2 - The current study addresses the morphoregulatory effects of human amyloid precursor protein expression on neocortical pyramidal cells in vivo. For this purpose, a transgenic mouse line was used that expresses wild-type human amyloid precursor protein (APP) at levels similar to endogenous mouse APP [introduced by Lamb, B.T., Sisodia, S.S., Lawler, A.M., Slunt, H.H., Kitt, C.A., Kearns, W.G., Pearson, P.L., Price, D.L., Gearhart, J.D., 1993. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat. Genet. 5, 22-30]. This strain does not develop Alzheimer's disease-related pathology which allowed to study effects of APP or APP cleavage products but excluded the influence of amyloid deposits. Commissural projecting pyramidal neurons of layers II/III within the primary somatosensory cortex were retrogradely labelled by injection of biotinylated dextran amine into the corpus callosum. In transgenic mice, computer-aided morphometric analysis revealed an increase in the surface area of proximal and intermediate basal dendritic segments resulting from an enlarged diameter. On the other hand, the length of the same segments was reduced. Both basal and apical dendrites were characterized by a higher dendritic density within the proximal and intermediate fields. Although the total spatial extension of basal and apical dendrites remained unchanged, a moderate withdrawal of arbors is suggested. The results implicate a physiological function for APP in regulatory mechanisms of neuronal morphogenesis.

AB - The current study addresses the morphoregulatory effects of human amyloid precursor protein expression on neocortical pyramidal cells in vivo. For this purpose, a transgenic mouse line was used that expresses wild-type human amyloid precursor protein (APP) at levels similar to endogenous mouse APP [introduced by Lamb, B.T., Sisodia, S.S., Lawler, A.M., Slunt, H.H., Kitt, C.A., Kearns, W.G., Pearson, P.L., Price, D.L., Gearhart, J.D., 1993. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat. Genet. 5, 22-30]. This strain does not develop Alzheimer's disease-related pathology which allowed to study effects of APP or APP cleavage products but excluded the influence of amyloid deposits. Commissural projecting pyramidal neurons of layers II/III within the primary somatosensory cortex were retrogradely labelled by injection of biotinylated dextran amine into the corpus callosum. In transgenic mice, computer-aided morphometric analysis revealed an increase in the surface area of proximal and intermediate basal dendritic segments resulting from an enlarged diameter. On the other hand, the length of the same segments was reduced. Both basal and apical dendrites were characterized by a higher dendritic density within the proximal and intermediate fields. Although the total spatial extension of basal and apical dendrites remained unchanged, a moderate withdrawal of arbors is suggested. The results implicate a physiological function for APP in regulatory mechanisms of neuronal morphogenesis.

KW - Alzheimer's disease

KW - Dendritic morphology

KW - Human amyloid precursor protein

UR - http://www.scopus.com/inward/record.url?scp=33644547351&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644547351&partnerID=8YFLogxK

U2 - 10.1016/j.ijdevneu.2005.11.008

DO - 10.1016/j.ijdevneu.2005.11.008

M3 - Article

C2 - 16384682

AN - SCOPUS:33644547351

VL - 24

SP - 133

EP - 140

JO - International Journal of Developmental Neuroscience

JF - International Journal of Developmental Neuroscience

SN - 0736-5748

IS - 2-3

ER -