BIOTIN DEFICIENCY FACILITATES KINDLING HYPEREXCITABILITY IN RATS

BIOTIN-DEFICIENT conditions are frequently associated with epileptic d isorders. Biotin deficiency may be caused by long-term treatment with anticonvulsants or excessive ingestion of avidin. Absence of biotinida se activity can also lead to biotin deficiency, and is characterized b y developmental delay as well as neurological and dermatological abnor malities. Because seizures are one of the most frequent signs of the l atter, biotin-deficient conditions could conceivably facilitate convul sive disorders. To test this hypothesis, we investigated the occurrenc e of a latent kindling hyperexcitability in biotin-deprived rats. In t hese animals, duration of afterdischarge on the first stimulation was longer at threshold amplitude, kindling development through its early stages was accelerated and duration of the forelimb clonus of fully ki ndled seizures was increased. Biotin deprivation in mixed cerebellar g ranule cell-astrocyte cultures also produced a tetrodotoxin-sensitive delayed loss of the glutamatergic neuronal population. The data thus s upport a facilitatory role for biotin-deficient conditions in convulsi ve disorders.