Abstract Details

Title Dynamic Changes of Ephrin A5/EphA4 Pathway in the Hippocampal Formation in a Mouse Model of Temporal Lobe Epilepsy

Topic Epilepsy

Presentation(s) P02 - (-)

Poster/Presentation
Number 215

Objective

Background BACKGROUND: Hippocampal structural abnormalities may result in epileptic network formation. Ephrin-A5/EphA4 signaling has been demonstrated to influence hippocampal neurogenesis and synaptogenesis during brain development, but its potential role in epileptogenesis has not yet been fully understood.

Design/Methods DESIGN/METHODS: Control and pilocarpine-induced epileptic male adult C57BL/6 mice were matched from same experimental groups. Ephrin-A5/EphA4 expression was examined with immunochemistry, and the dynamic changes at mRNA and protein levels were detected by quantitative real-time PCR and western blotting. The binding affinity of hippocampal Ephrin-A5/EphA4 was tested with co-immunoprecipitation. EphrinA5-Fc or vehicle was administered intraventricularly 3 days after status epilepticus (SE). The presence of doublecortin (DCX), which is specifically expressed in neuronal progenitor cells, was ascertained and the frequency of spontaneous seizures (SS) was studied.

Results RESULTS: In epileptic hippocampal formation, Ephrin-A5 immunoreactivity showed increased density especially in subgranluar zone (SGZ). Its overall expression increased at 2 weeks, and began to decrease at 8 weeks after SE. The protein expression of Ephrin-A5 showed a slight increase at 2 weeks, and was most prominent at 4 weeks after SE, and the mRNA level showed similar increase. A similar pattern of alteration was also found for EphA4 mRNA and protein expression. We found that Ephrin-A5 and EphA4 binding ability gradually increased at 2-4 weeks, and reached the peak in 8 weeks after SE. After the EphrinA5-Fc intraventricular injection, the DCX-immunoactive cells in the SGZ, at 2 weeks after SE, were reduced in number, exhibiting less branching morphology. Additionally, SS frequency decreased slightly.

Conclusions CONCLUSIONS: Ephrin-A5/EphA4 may be a potential pathway to regulate neurogenesis in adult hippocampal formation of temporal lobe epilepsy.

Authors/Disclosures
Sheila Chandrahas PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Bo Xiao (Xiangya Hospital Central-South University)	No disclosure on file
Charles Bernick, MD	Dr. Bernick has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Bernick has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Optina. Dr. Bernick has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Bernick has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corium. Dr. Bernick has stock in Aurora. The institution of Dr. Bernick has received research support from UFC. The institution of Dr. Bernick has received research support from Top Rank Promotions. The institution of Dr. Bernick has received research support from Haymon Boxing.

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