Endogenous and synthetic neuroactive steroids evoke sustained increases in the efficacy of GABAergic inhibition via a protein kinase C-dependent mechanism

Neuropharmacology

Volumn 113, Issue , 2017, Pages 314-322

  Modgil, Amit ^a   Parakala, Manasa L ^a   Ackley, Michael A ^b   Doherty, James J ^b   Moss, Stephen J ^a,c   Davies, Paul A ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Sage Therapeutics Inc   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Dentate gyrus; GABA receptor; Neuroactive steroid; Protein kinase C (PKC); Tonic inhibition

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR BETA3; GANAXOLONE; PROTEIN KINASE C; SGE 516; STEROID; TETRAHYDRODEOXYCORTICOSTERONE; UNCLASSIFIED DRUG; BISINDOLYLMALEIMIDE I; DEOXYCORTICOSTERONE; ELTANOLONE; ENZYME INHIBITOR; INDOLE DERIVATIVE; MALEIMIDE DERIVATIVE;

ALLOSTERISM; ANIMAL TISSUE; ARTICLE; BRAIN ELECTROPHYSIOLOGY; BRAIN SLICE; CONTROLLED STUDY; DENTATE GYRUS GRANULE CELL; ENZYME ACTIVITY; ENZYME INHIBITION; GABAERGIC SYSTEM; GRANULE CELL; HIPPOCAMPUS; MALE; MOUSE; NERVOUS SYSTEM PARAMETERS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TONIC CURRENT; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CHO CELL LINE; CRICETULUS; DRUG EFFECTS; HAMSTER; HEK293 CELL LINE; HUMAN; METABOLISM; NERVE CELL INHIBITION; ORGAN CULTURE TECHNIQUE; PHYSIOLOGY;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; DESOXYCORTICOSTERONE; ENZYME INHIBITORS; HEK293 CELLS; HIPPOCAMPUS; HUMANS; INDOLES; MALE; MALEIMIDES; MICE; MICE, INBRED C57BL; NEURAL INHIBITION; ORGAN CULTURE TECHNIQUES; PREGNANOLONE; PROTEIN KINASE C; RECEPTORS, GABA-A;

EID: 84993964801     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2016.10.010     Document Type: Article

References (29)

1. Abramian, A.M., Comenencia-Ortiz, E., Modgil, A., Vien, T.N., Nakamura, Y., Moore, Y.E., Maguire, J.L., Terunuma, M., Davies, P.A., Moss, S.J., Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 7132–7137.
2. Abramian, A.M., Comenencia-Ortiz, E., Vithlani, M., Tretter, E.V., Sieghart, W., Davies, P.A., Moss, S.J., Protein kinase C phosphorylation regulates membrane insertion of GABAA receptor subtypes that mediate tonic inhibition. J. Biol. Chem. 285 (2010), 41795–41805.
3. Adams, J.M., Thomas, P., Smart, T.G., Modulation of neurosteroid potentiation by protein kinases at synaptic- and extrasynaptic-type GABAA receptors. Neuropharmacology 88 (2015), 63–73.
4. Belelli, D., Harrison, N.L., Maguire, J., Macdonald, R.L., Walker, M.C., Cope, D.W., Extrasynaptic GABAA receptors: form, pharmacology, and function. J. Neurosci. 29 (2009), 12757–12763.
5. Bencsits, E., Ebert, V., Tretter, V., Sieghart, W., A significant part of native gamma-aminobutyric AcidA receptors containing alpha4 subunits do not contain gamma or delta subunits. J. Biol. Chem. 274 (1999), 19613–19616.
6. Botella, G.M., Salituro, F.G., Harrison, B.L., Beresis, R.T., Bai, Z., Shen, K.S., Belfort, G.M., Loya, C.M., Ackley, M.A., Grossman, S.J., Hoffmann, E., Jia, S.L., Wang, J.M., Doherty, J.J., Robichaud, A.J., Neuroactive steroids. 1. Positive allosteric modulators of the (gamma-aminobutyric acid)(A) receptor: structure-activity relationships of heterocyclic substitution at C-21. J. Med. Chem. 58 (2015), 3500–3511.
7. Brickley, S.G., Mody, I., Extrasynaptic GABA(A) receptors: their function in the CNS and implications for disease. Neuron 73 (2012), 23–34.
8. Bright, D.P., Smart, T.G., Protein kinase C regulates tonic GABA(A) receptor-mediated inhibition in the hippocampus and thalamus. Eur. J. Neurosci. 38 (2013), 3408–3423.
9. Caraiscos, V.B., Elliott, E.M., You-Ten, K.E., Cheng, V.Y., Belelli, D., Newell, J.G., Jackson, M.F., Lambert, J.J., Rosahl, T.W., Wafford, K.A., MacDonald, J.F., Orser, B.A., Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 3662–3667.
10. Chandra, D., Jia, F., Liang, J., Peng, Z., Suryanarayanan, A., Werner, D.F., Spigelman, I., Houser, C.R., Olsen, R.W., Harrison, N.L., Homanics, G.E., GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proc. Natl. Acad. Sci. U. S. A. 103 (2006), 15230–15235.
11. Curia, G., Papouin, T., Seguela, P., Avoli, M., Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome. Cereb. Cortex 19 (2009), 1515–1520.
12. D'Hulst, C., Kooy, R.F., The GABAA receptor: a novel target for treatment of fragile X?. Trends Neurosci. 30 (2007), 425–431.
13. Gantois, I., Vandesompele, J., Speleman, F., Reyniers, E., D'Hooge, R., Severijnen, L.A., Willemsen, R., Tassone, F., Kooy, R.F., Expression profiling suggests underexpression of the GABA(A) receptor subunit delta in the fragile X knockout mouse model. Neurobiol. Dis. 21 (2006), 346–357.
14. Glykys, J., Mody, I., Activation of GABAA receptors: views from outside the synaptic cleft. Neuron 56 (2007), 763–770.
15. Glykys, J., Peng, Z., Chandra, D., Homanics, G.E., Houser, C.R., Mody, I., A new naturally occurring GABA(A) receptor subunit partnership with high sensitivity to ethanol. Nat. Neurosci. 10 (2007), 40–48.
16. Herd, M.B., Haythornthwaite, A.R., Rosahl, T.W., Wafford, K.A., Homanics, G.E., Lambert, J.J., Belelli, D., The expression of GABAA beta subunit isoforms in synaptic and extrasynaptic receptor populations of mouse dentate gyrus granule cells. J. Physiol. 586 (2008), 989–1004.
17. Jovanovic, J.N., Thomas, P., Kittler, J.T., Smart, T.G., Moss, S.J., Brain-derived neurotrophic factor modulates fast synaptic inhibition by regulating GABA(A) receptor phosphorylation, activity, and cell-surface stability. J. Neurosci. 24 (2004), 522–530.
18. Kittler, J.T., Chen, G., Honing, S., Bogdanov, Y., McAinsh, K., Arancibia-Carcamo, I.L., Jovanovic, J.N., Pangalos, M.N., Haucke, V., Yan, Z., Moss, S.J., Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 14871–14876.
19. Kretschmannova, K., Hines, R.M., Revilla-Sanchez, R., Terunuma, M., Tretter, V., Jurd, R., Kelz, M.B., Moss, S.J., Davies, P.A., Enhanced tonic inhibition influences the hypnotic and amnestic actions of the intravenous anesthetics etomidate and propofol. J. Neurosci. 33 (2013), 7264–7273.
20. Maguire, J., Mody, I., GABA(A)R plasticity during pregnancy: relevance to postpartum depression. Neuron 59 (2008), 207–213.
21. Maldonado-Aviles, J.G., Curley, A.A., Hashimoto, T., Morrow, A.L., Ramsey, A.J., O'Donnell, P., Volk, D.W., Lewis, D.A., Altered markers of tonic inhibition in the dorsolateral prefrontal cortex of subjects with schizophrenia. Am. J. Psychiatry 166 (2009), 450–459.
22. Mitchell, E.A., Herd, M.B., Gunn, B.G., Lambert, J.J., Belelli, D., Neurosteroid modulation of GABAA receptors: molecular determinants and significance in health and disease. Neurochem. Int. 52 (2008), 588–595.
23. Mortensen, M., Smart, T.G., Extrasynaptic alphabeta subunit GABAA receptors on rat hippocampal pyramidal neurons. J. Physiol. 577 (2006), 841–856.
24. Nusser, Z., Mody, I., Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells. J. Neurophysiol. 87 (2002), 2624–2628.
25. Paul, S.M., Purdy, R.H., Neuroactive steroids. FASEB J. 6 (1992), 2311–2322.
26. Rupprecht, R., New perspectives in neurosteroid action: open questions for future research. Front. Cell Neurosci., 8, 2014, 268.
27. Semyanov, A., Walker, M.C., Kullmann, D.M., Silver, R.A., Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci. 27 (2004), 262–269.
28. Terunuma, M., Xu, J., Vithlani, M., Sieghart, W., Kittler, J., Pangalos, M., Haydon, P.G., Coulter, D.A., Moss, S.J., Deficits in phosphorylation of GABA(A) receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus. J. Neurosci. 28 (2008), 376–384.
29. Vien, T.N., Modgil, A., Abramian, A.M., Jurd, R., Walker, J., Brandon, N.J., Terunuma, M., Rudolph, U., Maguire, J., Davies, P.A., Moss, S.J., Compromising the phosphodependent regulation of the GABAAR beta3 subunit reproduces the core phenotypes of autism spectrum disorders. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 14805–14810.