The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice.
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. 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.
Alpár
Alán
A
Department of Anatomy, Histology and Embryology, Semmelweis University Medical School, Tuzoltó u. 58, H-1450 Budapest, Hungary.
Ueberham
Uwe
U
Brückner
Martina K
MK
Arendt
Thomas
T
Gärtner
Ulrich
U
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D048429:Cell Size; D003712:Dendrites / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology*; D010641:Phenotype; D017966:Pyramidal Cells / Q000166:cytology*
D016564:Amyloid beta-Protein Precursor