Seizure Susceptibility, Phenotype, and Resultant Growth Delay in the nclf and mnd Mouse Models of Neuronal Ceroid Lipofuscinoses

Abstract

We examined flurothyl gas–induced seizure latencies and phenotype in 2 mouse models of neuronal ceroid lipofuscinoses: the nclf ( Cln6 mutant) variant late-infantile model and the mnd ( Cln8 mutant) Northern epilepsy model. Mnd mice on postnatal days 35 to 42 had increased latency to loss of posture compared with wild-type controls. Nclf, mnd, and wild-type mice on postnatal days 21 days to 25 displayed similar latency profiles during repeated seizure induction (kindling) and retesting; seizure phenotypes were different, however. Kindled wild-type mice reexposed to flurothyl after a 28-day recovery displayed brainstem generalized seizures exclusively. Neuronal ceroid lipofuscinoses mutants demonstrated a lack of brainstem seizures at retesting after 28 days. Repeated induction of generalized seizures delayed weight gain in both nclf and mnd mice compared with wild-type mice. These and our previous results suggest that abnormal seizure-related neuronal connectivity and/or plasticity are shared characteristics of the neuronal ceroid lipofuscinoses.