Dual mechanisms of rapid expression of anxiety-related behavior in pilocarpine-treated epileptic mice

A mouse model of epilepsy was generated by inducing status epilepticus (SE) for either 1.5 or 4.5 h with pilocarpine to study anxiety-related behaviors, changes in the electroencephalogram of the cerebral cortex and hippocampus, and expression of hippocampal proteins. The viability and rate of success of SE induction were high in C57BL/6N mice but not in C57BL/6J mice. C57BL/6N mice were immotile during the first 2 days after SE; however, by the third day, most mice were recovered and exhibited strong anxiety-related behaviors in response to the light/dark preference test and open field test. There was a striking difference in the temporal appearance of anxiety-related behavior between the two SE durations: 1.5 h SE mice exhibited strong anxiety-related behavior 3 days after SE that gradually attenuated over the next few weeks, whereas 4.5 h SE mice exhibited strong anxiety-related behavior 3 days after SE that persisted even at nearly 1 year after SE. Mice receiving both SE durations exhibited generalized seizures (GS) after SE; however, there was a marked difference in the timing and duration of GS appearance. Mice in the 4.5 h SE group exhibited spontaneous GS from 4 days to at least 96 days after SE. In contrast, mice in the 1.5 h SE group exhibited GS only within the first several days after SE; however, epileptic spike clusters continuously appeared in the cerebral cortex and hippocampus for up to twelve days after SE. Among the hippocampal proteins tested, only brain derived-neurotrophic factor (BDNF) exhibited altered expression in parallel with anxiety-related behavior. These results showed the possibility that BDNF expression in the hippocampus might cause anxiety-related behavior in adulthood.