Ex vivo feedback control of neurotransmission using a photocaged adenosine A1 receptor agonist
- Author
- Erine Craey, Fabian Hulpia (UGent) , Jeroen Spanoghe (UGent) , Simona Manzella, Lars Emil Larsen (UGent) , Mathieu Sprengers (UGent) , Dimitri De Bundel, Ilse Smolders, Evelien Carrette (UGent) , Jean Delbeke (UGent) , Kristl Vonck (UGent) , Paul Boon (UGent) , Serge Van Calenbergh (UGent) , Wytse J. Wadman and Robrecht Raedt (UGent)
- Organization
- Project
-
- Strategies for boosting local adenosine A1 signaling as a treatment for focal epilepsy: from positive allosteric modulators of the inhibitory A1 receptor to deep brain stimulation and photopharmacology.
- Photoswitchable cannabinoids for precision treatment of refractory focal epileptic seizures
- NEON: Neuroprobe for Epilepsy treatment with Optogenetics.
- Abstract
- We report the design, synthesis, and validation of the novel compound photocaged N6-cyclopentyladenosine (cCPA) to achieve precisely localized and timed release of the parent adenosine A1 receptor agonist CPA using 405 nm light. Gi protein-coupled A1 receptors (A1Rs) modulate neurotransmission via pre- and post-synaptic routes. The dynamics of the CPA-mediated effect on neurotransmission, characterized by fast activation and slow recovery, make it possible to implement a closed-loop control paradigm. The strength of neurotransmission is monitored as the amplitude of stimulus-evoked local field potentials. It is used for feedback control of light to release CPA. This system makes it possible to regulate neurotransmission to a pre-defined level in acute hippocampal brain slices incubated with 3 µM cCPA. This novel approach of closed-loop photopharmacology holds therapeutic potential for fine-tuned control of neurotransmission in diseases associated with neuronal hyperexcitability.
- Keywords
- Adenosine A1 Receptor, caged compounds, hippocampus, photopharmacology, ADENOSINE RECEPTORS, HUMAN BRAIN, IN-VIVO, A(1), PHARMACOLOGY, HIPPOCAMPUS
Downloads
-
ijms-23-168887.pdf
- full text (Published version)
- |
- open access
- |
- |
- 1.97 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8763173
- MLA
- Craey, Erine, et al. “Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 23, no. 16, 2022, doi:10.3390/ijms23168887.
- APA
- Craey, E., Hulpia, F., Spanoghe, J., Manzella, S., Larsen, L. E., Sprengers, M., … Raedt, R. (2022). Ex vivo feedback control of neurotransmission using a photocaged adenosine A1 receptor agonist. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(16). https://doi.org/10.3390/ijms23168887
- Chicago author-date
- Craey, Erine, Fabian Hulpia, Jeroen Spanoghe, Simona Manzella, Lars Emil Larsen, Mathieu Sprengers, Dimitri De Bundel, et al. 2022. “Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 (16). https://doi.org/10.3390/ijms23168887.
- Chicago author-date (all authors)
- Craey, Erine, Fabian Hulpia, Jeroen Spanoghe, Simona Manzella, Lars Emil Larsen, Mathieu Sprengers, Dimitri De Bundel, Ilse Smolders, Evelien Carrette, Jean Delbeke, Kristl Vonck, Paul Boon, Serge Van Calenbergh, Wytse J. Wadman, and Robrecht Raedt. 2022. “Ex Vivo Feedback Control of Neurotransmission Using a Photocaged Adenosine A1 Receptor Agonist.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 (16). doi:10.3390/ijms23168887.
- Vancouver
- 1.Craey E, Hulpia F, Spanoghe J, Manzella S, Larsen LE, Sprengers M, et al. Ex vivo feedback control of neurotransmission using a photocaged adenosine A1 receptor agonist. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2022;23(16).
- IEEE
- [1]E. Craey et al., “Ex vivo feedback control of neurotransmission using a photocaged adenosine A1 receptor agonist,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 23, no. 16, 2022.
@article{8763173,
abstract = {{We report the design, synthesis, and validation of the novel compound photocaged N6-cyclopentyladenosine (cCPA) to achieve precisely localized and timed release of the parent adenosine A1 receptor agonist CPA using 405 nm light. Gi protein-coupled A1 receptors (A1Rs) modulate neurotransmission via pre- and post-synaptic routes. The dynamics of the CPA-mediated effect on neurotransmission, characterized by fast activation and slow recovery, make it possible to implement a closed-loop control paradigm. The strength of neurotransmission is monitored as the amplitude of stimulus-evoked local field potentials. It is used for feedback control of light to release CPA. This system makes it possible to regulate neurotransmission to a pre-defined level in acute hippocampal brain slices incubated with 3 µM cCPA. This novel approach of closed-loop photopharmacology holds therapeutic potential for fine-tuned control of neurotransmission in diseases associated with neuronal hyperexcitability.}},
articleno = {{8887}},
author = {{Craey, Erine and Hulpia, Fabian and Spanoghe, Jeroen and Manzella, Simona and Larsen, Lars Emil and Sprengers, Mathieu and De Bundel, Dimitri and Smolders, Ilse and Carrette, Evelien and Delbeke, Jean and Vonck, Kristl and Boon, Paul and Van Calenbergh, Serge and Wadman, Wytse J. and Raedt, Robrecht}},
issn = {{1422-0067}},
journal = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
keywords = {{Adenosine A1 Receptor,caged compounds,hippocampus,photopharmacology,ADENOSINE RECEPTORS,HUMAN BRAIN,IN-VIVO,A(1),PHARMACOLOGY,HIPPOCAMPUS}},
language = {{eng}},
number = {{16}},
pages = {{12}},
title = {{Ex vivo feedback control of neurotransmission using a photocaged adenosine A1 receptor agonist}},
url = {{http://doi.org/10.3390/ijms23168887}},
volume = {{23}},
year = {{2022}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: