Congruence of vascular network remodeling and neuronal dispersion in the hippocampus of reelin-deficient mice.

TY - JOUR

T1 - Congruence of vascular network remodeling and neuronal dispersion in the hippocampus of reelin-deficient mice.

AU - Lindhorst, Tina

AU - Kurz, Haymo

AU - Sibbe, Mirjam

AU - Meseke, Maurice

AU - Förster, Eckart

PY - 2012

Y1 - 2012

N2 - In the hippocampus, neurons and fiber projections are strictly organized in layers and supplied with oxygen via a vascular network that also develops layer-specific characteristics in wild-type mice, as shown in the present study for the first time in a quantitative manner. By contrast, in the reeler mutant, well known for its neuronal migration defects due to the lack of the extracellular matrix protein reelin, emerging layer-specific characteristics of the vascular pattern were found to be remodeled during development of the dentate gyrus. Remarkably, in the first postnatal week, when a granule cell layer was still discernable in the reeler dentate gyrus, also the reeler vascular pattern resembled wild type. Thus, at postnatal day 6, unbranched microvessels traversed the granule cell layer and bifurcated when reaching the subgranular zone. Only after the first postnatal week vascular network remodeling in the reeler dentate gyrus became apparent, when the proportion of dispersed granule cells increased. Hence, vessel bifurcation frequency decreased in the maturing reeler dentate gyrus, but increased in wild type, resulting in significant differences (approx. 100%; p <0.01) between adult wild type and reeler. Moreover, layer-specific vessel bifurcation frequencies disappeared in the maturing reeler dentate gyrus. Finally, a wild type-like vascular pattern was also found in the dentate gyrus of mice deficient for the reelin receptor very low density lipoprotein receptor (VLDLR), precluding a requirement of VLDLR for normal vascular pattern formation in the dentate gyrus. In sum, our findings show that vascular network remodeling in the reeler dentate gyrus is closely linked to the progression of granule cell dispersion.

AB - In the hippocampus, neurons and fiber projections are strictly organized in layers and supplied with oxygen via a vascular network that also develops layer-specific characteristics in wild-type mice, as shown in the present study for the first time in a quantitative manner. By contrast, in the reeler mutant, well known for its neuronal migration defects due to the lack of the extracellular matrix protein reelin, emerging layer-specific characteristics of the vascular pattern were found to be remodeled during development of the dentate gyrus. Remarkably, in the first postnatal week, when a granule cell layer was still discernable in the reeler dentate gyrus, also the reeler vascular pattern resembled wild type. Thus, at postnatal day 6, unbranched microvessels traversed the granule cell layer and bifurcated when reaching the subgranular zone. Only after the first postnatal week vascular network remodeling in the reeler dentate gyrus became apparent, when the proportion of dispersed granule cells increased. Hence, vessel bifurcation frequency decreased in the maturing reeler dentate gyrus, but increased in wild type, resulting in significant differences (approx. 100%; p <0.01) between adult wild type and reeler. Moreover, layer-specific vessel bifurcation frequencies disappeared in the maturing reeler dentate gyrus. Finally, a wild type-like vascular pattern was also found in the dentate gyrus of mice deficient for the reelin receptor very low density lipoprotein receptor (VLDLR), precluding a requirement of VLDLR for normal vascular pattern formation in the dentate gyrus. In sum, our findings show that vascular network remodeling in the reeler dentate gyrus is closely linked to the progression of granule cell dispersion.

KW - Animals

KW - Male

KW - Female

KW - Mice

KW - Mice, Knockout

KW - Mice, Inbred Strains

KW - Neurons/metabolism

KW - Models, Neurological

KW - Cell Adhesion Molecules, Neuronal/deficiency/metabolism

KW - Dentate Gyrus/blood supply/cytology/metabolism

KW - Extracellular Matrix Proteins/deficiency/metabolism

KW - Nerve Tissue Proteins/deficiency/metabolism

KW - Serine Endopeptidases/deficiency/metabolism

KW - Animals

KW - Male

KW - Female

KW - Mice

KW - Mice, Knockout

KW - Mice, Inbred Strains

KW - Neurons/metabolism

KW - Models, Neurological

KW - Cell Adhesion Molecules, Neuronal/deficiency/metabolism

KW - Dentate Gyrus/blood supply/cytology/metabolism

KW - Extracellular Matrix Proteins/deficiency/metabolism

KW - Nerve Tissue Proteins/deficiency/metabolism

KW - Serine Endopeptidases/deficiency/metabolism

M3 - SCORING: Journal article

VL - 137

SP - 629

EP - 639

JO - HISTOCHEM CELL BIOL

JF - HISTOCHEM CELL BIOL

SN - 0948-6143

IS - 5

M1 - 5

ER -