Cytoarchitectureal changes in hippocampal subregions of the NZB/W F1 mouse model of lupus

Abstract

Over 50% of clinical patients affected by the auto-immune disease lupus erythematosus display impaired neurological cognitive functions and psychiatric disorders, a form called neuropsychiatric systemic lupus erythematosus (NPSLE). The hippocampus is one of the brain structures most sensitive to the cognitive deficits and psychiatric disorders related to NPSLE. These deficits could arguably be related to changes in neuronal connectivity, which in turn are related to neuronal health and shape. The purpose of this study was to identify, layer by layer, possible structural alterations in seven hippocampal subregions: Molecular dentate gyrus (MoDG), Granular dentate gyrus (GrDG), Polymorph dentate gyrus (PoDG), Oriens layer (Or), Pyramidal layer (Py), Radiatum layer (Rad) and Lacunosum molecular layer (LMol), by comparing morphometric data from neural cells of digitalized Nissl-stained sections of the lupus mice model NZB/W F1 (NZBW) versus Wild Type mice (WT). Principal component analysis results showed a distinction in healthy WT from NZBW population, in which NZBW subjects showed scattered distributions and intra-subject variability. Moreover, NZBW neurons resulted larger (in PoDG, Or, Py, Rad LMol and GrDG), more regular and denser (in Or, Rad, LMol and MoDG) than in WT mice. The results presented here suggest that there is a hypertrophy of some of the NZBW mouse hippocampal neurons associated with an increase in variability of their perikaryal shape. Moreover, the differential affection of the laminar cytoarchitecture of the hippocampus suggests that the cell populations are differentially affected as well by NPSLE