Abstracts

Rationale: The role of glial involvement in addition to the modulating neural activity has been issued in the pathophysiology of epilepsy. However, the association between neuronal-glial interaction and comorbid behavioral abnormalities such as anxiety and/or depressive- symptoms in epilepsy has not established yet. This study investigated whether neurons and glia interact dynamically to lead behavioral consequences coexisting in temporal lobe epilepsy animal model. Methods: Male Sprague Dawley rats were induced status epilepticus (SE) for 2 hours by systemic injections of pilocarpine (360mg/kg), and were performed continuous video/EEG monitoring during and after the SE. Seizure severity was estimated spontaneous recurrent seizure (SRS) by modified Racine’s classification. Animals were tested for by open filed test (OFT), elevated plus maze (EPM), and forced swimming test (FST) to evaluate the associations between anxiety/depressive-like behaviors and epileptogenesis during chronic stage at 4 and 8weeks after the initial SE. After behavioral testing, the brains were sectioned for immunohistochemistry using neuronal nuclei antibodies (NeuN), and allograft inflammatory factor 1 (Iba-1) antibodies. Counting the NeuN- and Iba-1-immunopositive cells were averaged per the unit square (200X200 μm2) at each hippocampal subregion (subiculum, CA1, CA3, entorhinal cortex, and dentate gyrus). Results: Epileptic rats showed more depressive and anxiety-like behavior, especially at 8 weeks after the SE. Compared to the control group, epileptic rats showed more frequent total cross number and decreased center square duration times in OFT at 8 weeks after the SE, which means increased exploratory activity and more anxiety-like behaviors. Epileptic rats at 8 weeks after SE stayed shorter durations at open arms while longer durations at closed arms in the EPM, meaning increased anxiety-like behaviors at 4 and 8 weeks after the SE. In the FST, epileptic rats revealed longer immobility times at 4 and 8 weeks after the SE, meaning increased depression-like behaviors compared to the control group. In addition, NeuN reactive cells decreased in hippocampal CA1 and CA3 subregions , and Iba-1 positive glia cells increased in the hippocampal CA1 of epilepsy rats at 4 and 8 weeks after the SE. Conclusions: This study indicated that activated glial reaction during the epileptogenesis may also play an important role in the development of co-morbid psychiatric symptoms such as anxiety and depression. We are further investigating the relationship between glial-neuron interactions, epileptogenesis, and co-morbid anxiety or depressive behaviors, which can be helpful for treatment of seizures as well as co-existing psychiatric symptoms. Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and IT (2017R1A2A2A05069647, 2019M3C1B8090803 and 2019M3C1B8090902)