Characterizing longitudinal parvalbumin-positive interneuron vulnerability in rat model of Wolfram syndrome

Abstract

Wolfram syndrome type 1 (WS) is a rare autosomal recessive disorder characterized by early-onset diabetes mellitus, optic nerve and brainstem atrophy, deafness and neurodegeneration. This study utilized a genetically modified rat model of WS with a deletion of exon 5 in the Wfs1 gene to investigate the disease mechanisms and identify potential new therapeutic targets. The main aim of this thesis is to characterize the longitudinal vulnerability of parvalbumin-positive (PV+) interneurons in the hippocampus of Wolfram syndrome rat model. Results showed that WS rats have a consistently lower number of PV+ interneurons across age groups compared to wild-type littermates. Additionally, an age-related loss of perineuronal nets (PNNs) accompanied by increased parvalbumin expression were observed suggesting accelerated neurobiological aging. Moreover, elevated gliosis was observed, which indicates ongoing neuroinflammation.