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
