Abstract
Accumulating evidence suggests that morphological changes of subcellular-scale structures such as dendritic spine and mitochondria may be involved in the pathogenesis/pathophysiology of schizophrenia. Previously, we have proposed mice lacking Schnurri-2 (Shn2), an MHC enhancer binding protein, as a schizophrenia model with mild chronic inflammation. In the mutants, there are decreases in the expression level of PSD95, synaptic marker, and increases in C1q family genes (C1qa, C1qc and C1ql2), which are considered to mediate synapse elimination during the postnatal development. In the present study, we analyzed three-dimensional morphological changes in dendritic spines and mitochondria in dentate gyrus granule cells in Shn2 KO mice by serial block-face scanning electron microscopy. The mutants showed about 13% increase in spine length, and about 25% increase in spine neck length. There were no significant differences between Shn2 KO and wild-type mice in their spine density, volume of spine, spine head length, or spine head diameter. The mutants exhibited reduced complexity in mitochondrial morphology, suggesting that a balance between mitochondrial fusion and fission is compromised in Shn2 KO mice. These morphological changes in spines and mitochondria may be associated with functional impairments of those subcellular-scale structures, and represent potential endophenotype of schizophrenia.