TY  - JOUR
AU  - Schneider-Lódi, Mária
AU  - Ahrari, Ala
AU  - Meseke, Maurice
AU  - Corvace, Franco
AU  - Kümmel, Marie-Luise
AU  - Trampe, Anne-Kathrin
AU  - Hamad, Mohammad I K
AU  - Förster, Eckart
TI  - Early Postnatally Induced Conditional Reelin Deficiency Causes Malformations of Hippocampal Neurons.
JO  - Biomolecules
VL  - 15
IS  - 12
SN  - 2218-273X
CY  - Basel
PB  - MDPI
M1  - DZNE-2025-01509
SP  - 1662
PY  - 2025
AB  - The extracellular matrix protein reelin is well known for orchestrating radial migration of cortical neurons during embryonic cortical development. While in the reeler mutant mouse, lacking reelin expression, radially migrating neurons are malpositioned and display dendritic malformations, no such deficits were found after conditionally induced reelin deficiency (RelncKO) in the hippocampus of mice aged two months. Here, we addressed the question whether or not RelncKO, when induced early after birth, might cause malformations of hippocampal neurons. For instance, we could recently show dendritic hypertrophy of somatosensory and entorhinal cortex neurons after early induced RelncKO. In the present study, reelin deficiency in RelncKO mice was induced immediately after birth, and the analysis of reconstructed Golgi-stained hippocampal neurons from these mice, when aged 4 weeks, revealed morphological malformations. Dentate granule cells were the most affected from all analyzed hippocampal neuronal cell types. Thus, RelncKO granule cells had a significantly smaller soma size and displayed atrophy of proximal dendritic segments when compared to wild type (wt). Malformations of interneurons were only subtle and cell type specific; thus, multipolar but not bitufted interneurons developed proximal dendritic hypertrophy. Also, the dendrite morphology of CA2- and CA3-pyramidal cells was affected, while we did not detect morphological changes of CA1-pyramidal cell dendrites. In summary, our results show that early postnatal RelncKO causes morphological malformations of hippocampal neurons, in particular of dentate granule cells. Taken together with our previous findings, we conclude that not only specific types of entorhinal- and neocortical neurons, but also types of hippocampal neurons are at risk of developing malformations if reelin expression is reduced during a critical early postnatal period.
KW  - Animals
KW  - Reelin Protein
KW  - Hippocampus: metabolism
KW  - Hippocampus: pathology
KW  - Serine Endopeptidases: deficiency
KW  - Serine Endopeptidases: genetics
KW  - Serine Endopeptidases: metabolism
KW  - Cell Adhesion Molecules, Neuronal: deficiency
KW  - Cell Adhesion Molecules, Neuronal: genetics
KW  - Cell Adhesion Molecules, Neuronal: metabolism
KW  - Nerve Tissue Proteins: deficiency
KW  - Nerve Tissue Proteins: genetics
KW  - Nerve Tissue Proteins: metabolism
KW  - Extracellular Matrix Proteins: deficiency
KW  - Extracellular Matrix Proteins: genetics
KW  - Extracellular Matrix Proteins: metabolism
KW  - Mice
KW  - Neurons: metabolism
KW  - Neurons: pathology
KW  - Mice, Knockout
KW  - Dendrites: metabolism
KW  - Dendrites: pathology
KW  - dendritic morphology (Other)
KW  - granule cells (Other)
KW  - hippocampus (Other)
KW  - interneurons (Other)
KW  - knock-out (Other)
KW  - neuron reconstruction (Other)
KW  - pyramidal cells (Other)
KW  - reelin (Other)
KW  - silver staining (Other)
KW  - Reelin Protein (NLM Chemicals)
KW  - Reln protein, mouse (NLM Chemicals)
KW  - Serine Endopeptidases (NLM Chemicals)
KW  - Cell Adhesion Molecules, Neuronal (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Extracellular Matrix Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41463318
DO  - DOI:10.3390/biom15121662
UR  - https://pub.dzne.de/record/283102
ER  -