@inproceedings{01J1VS966BBEN8EKDM73ANCJD1,
  abstract     = {{Introduction: The adenosine A1 receptor (A1R) is a promising therapeutic target in epilepsy by
mediating neuronal inhibition. In this study, we investigated whether A1R signaling is still functional
in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). The
feasibility of spatial selective inhibition was evaluated by illumination of specific hippocampal
subregions for optical uncaging of CPA from coumarin-caged CPA (cCPA). 

Methods: In the CA1 and DG of acute hippocampal slices, the effect of adding 40 nM of the A1R
agonist N6cyclopentyladenosine (CPA) on population spike (PS) amplitude to field postsynaptic
potential (fPSP) slope, an index of excitability, was evaluated in epileptic IHKA versus healthy mice.
Subregion selective inhibition of fPSPs was evaluated through application of 405nm light pulses (10
pulses of 100ms at 0.1Hz) spatially restricted to CA1 or DG of healthy slices incubated with 3µM
cCPA. 

Results: Administration of CPA resulted in a similar decrease in PS amplitude to fPSP slope ratio in
epileptic versus healthy mice for the CA1 and DG (n=19, Figure1). In a slice incubated with cCPA,
the excitability decreased selectively in the illuminated hippocampal subregion (n=1, Figure2). 

Conclusion: The decrease in excitability is comparable in hippocampal slices of IHKA versus healthy
mice upon exposure to CPA, indicating preserved A1R signaling in IHKA mice. The use of cCPA allows
modulation of hippocampal subregions through localized illumination. These results indicate that
photopharmacology has the potential to become a targeted therapy for TLE.}},
  articleno    = {{EPO-520}},
  author       = {{Vergaelen, Marijke and Spanoghe, Jeroen and Missinne, Jeroen and Van Calenbergh, Serge and Vonck, Kristl and Boon, Paul and Raedt, Robrecht}},
  booktitle    = {{EUROPEAN JOURNAL OF NEUROLOGY}},
  issn         = {{1351-5101}},
  keywords     = {{Epilepsy}},
  language     = {{eng}},
  location     = {{Helsinki, Finland}},
  number       = {{Supplement 1}},
  pages        = {{EPO-520:296--EPO-520:297}},
  title        = {{Towards therapeutic innovation in temporal lobe epilepsy : focal adenosinergic modulation of hippocampal excitability}},
  url          = {{https://www.ean.org/meet/congresses/congress-2024-helsinki}},
  volume       = {{31}},
  year         = {{2024}},
}