Abstracts

Rationale: In the rodent model of TLE, there is massive reorganization within the hippocampus during the latent period following a single prolonged seizure event, after which the animal develops spontaneous seizures (or epilepsy). The perineuronal net (PN), a subcomponent of the neural extracellular matrix (ECM), mediates the decrease in synaptic plasticity by enveloping the synapses and providing stabilization in the mature central nervous system. The PN component of the ECM is primarily around inhibitory interneurons and under normal conditions restricts cellular reorganization. The objective of the current study was to explore how the PNs change as an animal develops epilepsy. Methods: Status epileptics (SE) was induced using pilocarpine in adult male rats and PN expression was detected with the antibody Cat-315, which detects the aggrecan component of the PN, acutely (48 hours after SE), during the latent period (1 week post SE), and during the chronic period (2 months post SE). ADAMTS4 Western blots and immunohistochemistry was also performed. Results: The aggrecan component of the PN decreases within a week of SE, and aggrecan expression remained attenuated at 2 months. The percent of parvalbumin expressing interneurons with an intact PN is decreased throughout the hippocampus. Aggrecan mRNA levels do not decrease following SE, suggesting that the decrease in aggrecan protein is not due to diminished production. We further demonstrate that the decrease in PN expression is concurrent with an increase in matrix specific proteases capable of degrading aggrecan, specifically ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs). Conclusions: Following SE there is loss of the aggrecan component of the PN in the hippocampus and an increase in proteases capable of degrading the PN. This likely promotes neuronal reorganization that might contribute to the development of epilepsy. These studies are the foundation for understanding how changes in the ECM following SE contribute to the development of epilepsy. Grant/Other Support:CURE Postdoctoral Fellow Taking Flight Award, NIH Research Supplement R01NS05622-03S1, Neurodevelopmental Disabilities Training Grant T32NS07413-10