<p>A. AICD-Tg mice exhibit increased sensitivity towards Kainic Acid (KA)-mediated seizures at 3–4 months of age. Animals were injected with a sub-threshold dose of KA (20 mg/kg) and observed for 60 minutes for seizure–like hyperactivity. Seizures were scored according to a modified Racine scale. AICD-Tg mice began to show significant signs of seizures at 30 min. However, lack of tau (Tau-/-) significantly protected AICD-Tg mice against KA-mediated seizure-like hyperactivity. Tau-/- mice behaved similar to wild-type (WT) littermates. B. The time taken to reach level 4–5 seizures was scored as the latency to reach convulsive seizures. Lack of tau (Tau-/-) had a protective effect on AICD transgenic animals. C. Mean seizure severity scores showed a significant rescue of seizure severity by Tau-/- in AICD animals. n = 4–5 mice per group (A-C). D. Sagittal sections from 4-month-old WT and AICD-Tg mice were stained with NeuN antibody. Arrows show the loss of neurons in the CA3 region of AICD-Tg mice. Deletion of Tau protected AICD-Tg mice from KA-mediated neuronal loss. E. Quantification of NeuN-positive cells shows that Tau-/- makes AICD-Tg mice resistant to KA-mediated neurodegeneration. F. AICD-Tg mice show an increase in neuropeptide-Y (NPY) expression in mossy fiber terminals (arrows) following KA-mediated seizures. Tau deletion decreased NPY expression in mossy fiber terminals following KA injection in AICD-Tg animals. G. Quantification of NPY immunoreactivity normalized to WT animals. *p<0.05, **p<0.01, ***p<0.001, one way ANOVA (all data expressed as Mean ± SEM). n = 5 for all groups (D-G). Scale bar = 50 μm (D) and100 μm (F).</p
