Cytoarchitectural and immunocytochemical alterations in hippocampal subregions of the lupus model NZB/W F1 mice

Systemic lupus erythematosus (SLE) often impacts brain function, causing cognitive impairment and psychiatric disorders, referred to as neuropsychiatric SLE (NSLE). This research compares the neuronal morphology of SLE mouse models (NZB/W F1) and wild-type (WT) mice in the hippocampus, a brain area exhibiting significant effects from NSLE. Nissl-stained sections were processed via a deep learning method to outline individual cells, with and without Calcium Binding Proteins (CBPs). Morphological and density features were extracted at the cellular level, and cells were classified into distinct shape groups, to investigate the minute structural differences between NSLE and WT mice across the molecular dentate, granular dentate, and polymorph dentate gyrus, oriens, pyramidal, radiatum and lacunosum molecular layers. In NSLE mice, neurons exhibited larger size and greater regularity compared to those in WT mice. Additionally, neurons tended to be denser in NSLE mice overall, though the pyramidal layer neurons were denser in WT mice compared to NSLE mice. Subtle differences were also observed in CBPs. Our findings indicate an increase in perikaryal size of specific neuron types and hippocampal layers in the lupus mouse model NZB/W F1 and slight changes in the distribution and intensity of CBPs. PCA effectively differentiated NSLE mice from the WT group. Through high-throughput analysis of neuron morphology in hippocampal subregions, we propose a novel pipeline for comparing pathological and WT mice. Our results suggest that distinct subregions may be differentially affected by NSLE-induced inflammation, contributing to a better comprehension of hippocampal organization and structure in the NSLE model.