Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia

Reelin, an extracellular matrix protein, is secreted by Cajal-Retzius cells and plays crucial roles in the development of brain structures neuronal functions. Reductions Reelin cause dysfunctions associated with mental disorders, such as schizophrenia. A recent genome-wide copy number variation analysis Japanese schizophrenia patients identified a novel deletion RELN encoding Reelin. To clarify pathophysiological role deletion, we developed transgenic mice carrying (Reln-del) found abnormalities their social behavior. In present study, performed vitro expression, intracellular signaling, morphology primary cultured cortical neurons from wild-type (WT) Reln-del mice. protein levels were lower than WT neurons. Dab1 expression significantly higher neurons, suggesting that signaling was decreased mainly expressed γ-aminobutyric acid (GABA)-ergic inhibitory but not parvalbumin (PV)-positive small proportion Ca2+/calmodulin-dependent kinase II α subunit (CaMKIIα)-positive excitatory also comparisons significant decreases observed neurite lengths branch points well postsynaptic density 95 (PSD95) immunoreactive puncta disintegrin metalloproteinase thrombospondin motifs-3 (ADAMTS-3) protease inactivates cleavage at N-t site. The knockdown ADAMTS-3 short hairpin RNAs suppressed conditioned medium reduced indicating enhanced heterozygous Reln-del. Accordingly, inhibition may be potential candidate clinical treatment enhancing brain.