THE COURSE OF PARVALBUMIN-POSITIVE GABAERGIC INTERNEURONS IN THE DORSAL HIPPOCAMPUS OF SOD1 MUTANT MICE

Cognitive impairments have been recently described in the amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease. However, limited attention has been yet devoted to the study of cortical and hippocampal damages in the mouse model of ALS, SOD1 (G93A). We hypothesized possible association between cognitive impairment and changes of hippocampal GABAergic system in SOD1 mice. We analyzed SOD1 mice at presymptomatic (n=6, aged 13 weeks) and symptomatic (n=6, aged 18 weeks) states, and wild-type mice (n=6, aged 8-12 weeks). Animals were anaesthetized and perfused transcardially by 4% paraformaldehyde. Brain sections were immunohistochemically processed to visualize the largest class of interneurons of the hippocampal formation, the parvalbumin-immunopositive (PVi) GABAergic interneurons. After image acquisition, the hippocampus was reconstructed and analyzed with ImageJ (NIH). In SOD1 mice of both groups the number of PVi neurons was reduced by onethird to two-third. The decrease of PVi cells involved all hippocampal subregions. Interestingly, the PVi cell population was reduced already at presymptomatic stage, well before evidences for impairment of motor behaviors. Our findings situate hippocampus changes in SOD1 as starting point of the pathological chain of events, with potential implications on diagnosis and treatment of ALS.