Brain mechanisms of GHB and GABAergic
signalling in the Wellendorph Lab
Our lab is devoted to understanding brain mechanisms involving the inhibitory neurotransmitter GABA (γ-aminobutyric acid) and its metabolite GHB (γ-hydroxybutyric acid). We use biochemical and pharmacological analyses in cells, tissues
Another focus area is GABAA receptors and their role in brain excitability governed by tonic inhibition using novel ligands and pharmacological assays.
We also work on SLC6A GABA transporters and how they regulate GABA neurotransmitter levels, particularly in cerebral ischemia.
- Identification of the ubiquitous neuronal
signallingmolecule CaMKIIα as the physiological target for GHB
- Identification and characterization of extrasynaptic GABAA receptors
- Drug discovery into and anti-ischemic effects of GABA transporter ligands
- Leurs U, Klein AB, McSpadden ED, Griem-Krey N, Solbak SMØ, Houlton J, Villumsen IS, Vogensen SB, Hamborg, L, Gauger SJ, Palmelund LB, Larsen ASG, Shehata MA, Kelstrup CD, Olsen, JV, Bach A, Burnie RO, Kerr S, Gowing EK, Teurlings SMW, Chi CC, Gee CL, Frølund B, Kornum BR, van Woerden GM, Clausen RP, Kuriyan J, Clarkson AN & Wellendorph P. GHB confers neuroprotection by stabilizing the
hub domain. bioRxiv
- Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, Knudsen GM, Bräuner-Osborne H, Frølund B, Clausen RP, Chebib M & Wellendorph P (2012). a4bd GABAA receptors are high-affinity targets for g-hydroxybutyric acid (GHB). Proc. Natl. Acad. Sci USA 109: 13404-13409.
- Dalby NO, Leurs U, Falk-Petersen C, Scholze P, Krall J, Frølund & *Wellendorph P. Silencing of spontaneous activity at α4β1/3δ GABAA receptors in hippocampal granule cells reveals different ligand pharmacology. Br. J. Pharmacol. 2020 Jun 2. 177: 3975-3990 (2020).
- Falk-Petersen CB, Tsonkov T, Nielsen M, Harpsøe K, Bundgaard C, Frølund B, Kristiansen U, Gloriam D & Wellendorph P (2020). Discovery of a new class of orthosteric antagonists with nanomolar potency at extrasynaptic GABAA receptors. Sci. Rep. 10:10078.
- Lie MEK, Gowing EK, Johansen NB, Dalby NO, Thiesen L, Wellendorph P & Clarkson A (2018). The GAT3 selective substrate L-
isoserineupregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice. J. Cereb. Blood Flow Metab. 38: 166-173.
Lie MEK, Al-Khawaja A, Damgaard M, Haugaard AS, Schousboe A, Clarkson AN, Wellendorph P (2017). Glial transporters as modulators of inhibitory
signallingin epilepsy and stroke. Adv Neurobiol. Adv. Neurobiol. 16:137-167. doi: 10.1007/978-3-319-55769-4_7.
- Hørslev Foundation
- Independent Research Fund Denmark
- The Novo Nordisk Foundation