Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome (original) (raw)

• Dierssen, M. Down syndrome: the brain in trisomic mode. Nat. Rev. Neurosci. 13, 844–858 (2012).
  CAS PubMed Google Scholar
• Reeves, R.H. et al. A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat. Genet. 11, 177–184 (1995).
  CAS PubMed Google Scholar
• Costa, A.C. & Grybko, M.J. Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome. Neurosci. Lett. 382, 317–322 (2005).
  CAS PubMed Google Scholar
• Fernandez, F. et al. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat. Neurosci. 10, 411–413 (2007).
  CAS PubMed Google Scholar
• Costa, A.C., Scott-McKean, J.J. & Stasko, M.R. Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test. Neuropsychopharmacology 33, 1624–1632 (2008).
  CAS PubMed Google Scholar
• Chakrabarti, L. et al. Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat. Neurosci. 13, 927–934 (2010).
  CAS PubMed PubMed Central Google Scholar
• Kleschevnikov, A.M. et al. Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J. Neurosci. 24, 8153–8160 (2004).
  CAS PubMed PubMed Central Google Scholar
• Kleschevnikov, A.M. et al. Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. Neurobiol. Dis. 45, 683–691 (2012).
  CAS PubMed Google Scholar
• Costa, A.C. & Scott-McKean, J.J. Prospects for improving brain function in individuals with Down syndrome. CNS Drugs 27, 679–702 (2013).
  CAS PubMed Google Scholar
• Braudeau, J. et al. Specific targeting of the GABA-A receptor alpha5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice. J. Psychopharmacol. 25, 1030–1042 (2011).
  CAS PubMed PubMed Central Google Scholar
• Szemes, M., Davies, R.L., Garden, C.L. & Usowicz, M.M. Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down's syndrome. Mol. Brain 6, 33 (2013).
  CAS PubMed PubMed Central Google Scholar
• Best, T.K., Cramer, N.P., Chakrabarti, L., Haydar, T.F. & Galdzicki, Z. Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome. Exp. Neurol. 233, 749–757 (2012).
  CAS PubMed Google Scholar
• Mitra, A., Blank, M. & Madison, D.V. Developmentally altered inhibition in Ts65Dn, a mouse model of Down syndrome. Brain Res. 1440, 1–8 (2012).
  CAS PubMed PubMed Central Google Scholar
• Hanson, J.E., Blank, M., Valenzuela, R.A., Garner, C.C. & Madison, D.V. The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down's syndrome. J. Physiol. (Lond.) 579, 53–67 (2007).
  CAS Google Scholar
• Harashima, C. et al. Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome. J. Comp. Neurol. 494, 815–833 (2006).
  CAS PubMed PubMed Central Google Scholar
• Cancedda, L., Fiumelli, H., Chen, K. & Poo, M.M. Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo. J. Neurosci. 27, 5224–5235 (2007).
  CAS PubMed PubMed Central Google Scholar
• Deidda, G., Bozarth, I.F. & Cancedda, L. Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives. Front. Cell. Neurosci. 8, 119 (2014).
  PubMed PubMed Central Google Scholar
• Ward, O.C. & Lam, L.K. Bumetanide in heart failure in infancy. Arch. Dis. Child. 52, 877–882 (1977).
  CAS PubMed PubMed Central Google Scholar
• Maa, E.H., Kahle, K.T., Walcott, B.P., Spitz, M.C. & Staley, K.J. Diuretics and epilepsy: will the past and present meet? Epilepsia 52, 1559–1569 (2011).
  CAS PubMed Google Scholar
• Fiumelli, H., Cancedda, L. & Poo, M.M. Modulation of GABAergic transmission by activity via postsynaptic Ca2+-dependent regulation of KCC2 function. Neuron 48, 773–786 (2005).
  CAS PubMed Google Scholar
• Doyon, N. et al. Efficacy of synaptic inhibition depends on multiple, dynamically interacting mechanisms implicated in chloride homeostasis. PLoS Comput. Biol. 7, e1002149 (2011).
  CAS PubMed PubMed Central Google Scholar
• Succol, F., Fiumelli, H., Benfenati, F., Cancedda, L. & Barberis, A. Intracellular chloride concentration influences the GABAA receptor subunit composition. Nat. Commun. 3, 738 (2012).
  PubMed Google Scholar
• Rissman, R.A. & Mobley, W.C. Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer's disease. J. Neurochem. 117, 613–622 (2011).
  CAS PubMed PubMed Central Google Scholar
• Pueschel, S.M., Louis, S. & McKnight, P. Seizure disorders in Down syndrome. Arch. Neurol. 48, 318–320 (1991).
  CAS PubMed Google Scholar
• Westmark, C.J., Westmark, P.R. & Malter, J.S. Alzheimer's disease and Down syndrome rodent models exhibit audiogenic seizures. J. Alzheimers Dis. 20, 1009–1013 (2010).
  CAS PubMed PubMed Central Google Scholar
• Danglot, L., Triller, A. & Marty, S. The development of hippocampal interneurons in rodents. Hippocampus 16, 1032–1060 (2006).
  CAS PubMed Google Scholar
• Alger, B.E. Gating of GABAergic inhibition in hippocampal pyramidal cells. Ann. NY Acad. Sci. 627, 249–263 (1991).
  CAS PubMed Google Scholar
• Usowicz, M.M. & Garden, C.L. Increased excitability and altered action potential waveform in cerebellar granule neurons of the Ts65Dn mouse model of Down syndrome. Brain Res. 1465, 10–17 (2012).
  CAS PubMed PubMed Central Google Scholar
• Wlodarczyk, A.I. et al. Tonic GABAA conductance decreases membrane time constant and increases EPSP-spike precision in hippocampal pyramidal neurons. Front. Neural Circuits 7, 205 (2013).
  PubMed PubMed Central Google Scholar
• Jean-Xavier, C., Mentis, G.Z., O'Donovan, M.J., Cattaert, D. & Vinay, L. Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Proc. Natl. Acad. Sci. USA 104, 11477–11482 (2007).
  CAS PubMed PubMed Central Google Scholar
• Song, I., Savtchenko, L. & Semyanov, A. Tonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons. Nat. Commun. 2, 376 (2011).
  PubMed Google Scholar
• Duchon, A. et al. Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling Down syndrome. Mamm. Genome 22, 674–684 (2011).
  CAS PubMed PubMed Central Google Scholar
• Lemonnier, E. et al. A randomised controlled trial of bumetanide in the treatment of autism in children. Transl. Psychiatry 2, e202 (2012).
  CAS PubMed PubMed Central Google Scholar
• Ward, A. & Heel, R.C. Bumetanide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 28, 426–464 (1984).
  CAS PubMed Google Scholar
• Puskarjov, M., Kahle, K.T., Ruusuvuori, E. & Kaila, K. Pharmacotherapeutic targeting of cation-chloride cotransporters in neonatal seizures. Epilepsia 55, 806–818 (2014).
  CAS PubMed PubMed Central Google Scholar
• Li, Y. et al. Sensitive isotope dilution liquid chromatography/tandem mass spectrometry method for quantitative analysis of bumetanide in serum and brain tissue. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 879, 998–1002 (2011).
  CAS PubMed PubMed Central Google Scholar
• Cleary, R.T. et al. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures. PLoS One 8, e57148 (2013).
  CAS PubMed PubMed Central Google Scholar
• Deidda, G. et al. Early depolarizing GABA controls critical-period plasticity in the rat visual cortex. Nat. Neurosci. 18, 87–96 (2015).
  CAS PubMed Google Scholar
• Dzhala, V.I. et al. NKCC1 transporter facilitates seizures in the developing brain. Nat. Med. 11, 1205–1213 (2005).
  CAS PubMed Google Scholar
• Sipilä, S.T., Schuchmann, S., Voipio, J., Yamada, J. & Kaila, K. The cation-chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat hippocampus. J. Physiol. 573, 765–773 (2006).
  PubMed PubMed Central Google Scholar
• Kahle, K.T., Barnett, S.M., Sassower, K.C. & Staley, K.J. Decreased seizure activity in a human neonate treated with bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) cotransporter NKCC1. J. Child Neurol. 24, 572–576 (2009).
  PubMed Google Scholar
• Mazarati, A., Shin, D. & Sankar, R. Bumetanide inhibits rapid kindling in neonatal rats. Epilepsia 50, 2117–2122 (2009).
  CAS PubMed PubMed Central Google Scholar
• Edwards, D.A. et al. Bumetanide alleviates epileptogenic and neurotoxic effects of sevoflurane in neonatal rat brain. Anesthesiology 112, 567–575 (2010).
  CAS PubMed Google Scholar
• Lemonnier, E. & Ben-Ari, Y. The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects. Acta Paediatr. 99, 1885–1888 (2010).
  PubMed Google Scholar
• Lemonnier, E. et al. Treating Fragile X syndrome with the diuretic bumetanide: a case report. Acta Paediatr. 102, e288–e290 (2013).
  PubMed Google Scholar
• Tyzio, R. et al. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science 343, 675–679 (2014).
  CAS PubMed Google Scholar
• Hadjikhani, N. et al. Improving emotional face perception in autism with diuretic bumetanide: a proof-of-concept behavioral and functional brain imaging pilot study. Autism 19, 149–157 (2013).
  PubMed Google Scholar
• Mares, P. Age- and dose-specific anticonvulsant action of bumetanide in immature rats. Physiol. Res. 58, 927–930 (2009).
  CAS PubMed Google Scholar
• Brandt, C., Nozadze, M., Heuchert, N., Rattka, M. & Loscher, W. Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy. J. Neurosci. 30, 8602–8612 (2010).
  CAS PubMed PubMed Central Google Scholar
• Wang, D.D. & Kriegstein, A.R. Blocking early GABA depolarization with bumetanide results in permanent alterations in cortical circuits and sensorimotor gating deficits. Cereb. Cortex 21, 574–587 (2011).
  PubMed Google Scholar
• Validus Pharmaceuticals Bumex: brand of bumetanide tablets. Drugs@FDA: FDA Approved Drug Products http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018225s024lbl.pdf (2008).
• Pentikäinen, P.J., Penttilä, A., Neuvonen, P. & Gothoni, G. Fate of [14C]-bumetanide in man. Br. J. Clin. Pharmacol. 4, 39–44 (1977).
  PubMed PubMed Central Google Scholar
• Ostergaard, E.H., Magnussen, M.P., Nielsen, C.K., Eilertsen, E. & Frey, H.H. Pharmacological properties of 3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid (Bumetanide), a new potent diuretic. Arzneimittelforschung 22, 66–72 (1972).
  CAS PubMed Google Scholar
• Löscher, W., Puskarjov, M. & Kaila, K. Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments. Neuropharmacology 69, 62–74 (2013).
  PubMed Google Scholar
• Strittmatter, S.M. Overcoming drug development bottlenecks with repurposing: old drugs learn new tricks. Nat. Med. 20, 590–591 (2014).
  CAS PubMed PubMed Central Google Scholar
• He, Q., Nomura, T., Xu, J. & Contractor, A. The developmental switch in GABA polarity is delayed in fragile X mice. J. Neurosci. 34, 446–450 (2014).
  CAS PubMed PubMed Central Google Scholar
• Ehninger, D. et al. Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis. Nat. Med. 14, 843–848 (2008).
  CAS PubMed PubMed Central Google Scholar
• Han, S. et al. Autistic-like behaviour in Scn1a+/− mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489, 385–390 (2012).
  CAS PubMed PubMed Central Google Scholar
• Castrén, E., Elgersma, Y., Maffei, L. & Hagerman, R. Treatment of neurodevelopmental disorders in adulthood. J. Neurosci. 32, 14074–14079 (2012).
  PubMed PubMed Central Google Scholar
• Contestabile, A. et al. Lithium rescues synaptic plasticity and memory in Down syndrome mice. J. Clin. Invest. 123, 348–361 (2013).
  CAS PubMed Google Scholar
• Peça, J. et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472, 437–442 (2011).
  PubMed PubMed Central Google Scholar
• Verkman, A.S., Sellers, M.C., Chao, A.C., Leung, T. & Ketcham, R. Synthesis and characterization of improved chloride-sensitive fluorescent indicators for biological applications. Anal. Biochem. 178, 355–361 (1989).
  CAS PubMed Google Scholar
• Westmark, C.J. et al. Reversal of fragile X phenotypes by manipulation of AbetaPP/Abeta levels in Fmr1KO mice. PLoS ONE 6, e26549 (2011).
  CAS PubMed PubMed Central Google Scholar
• Peterson, S.L. & Albertson, T.E. Neuropharmacology Methods in Epilepsy Research (CRC Press, 1998).
• Hallett, P.J., Collins, T.L., Standaert, D.G. & Dunah, A.W. Biochemical fractionation of brain tissue for studies of receptor distribution and trafficking. Curr. Protoc. Neurosci. Chapter 1, Unit 1.16 (2008).
• Thomas-Crusells, J., Vieira, A., Saarma, M. & Rivera, C. A novel method for monitoring surface membrane trafficking on hippocampal acute slice preparation. J. Neurosci. Methods 125, 159–166 (2003).
  CAS PubMed Google Scholar
• Bustin, S.A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611–622 (2009).
  CAS PubMed Google Scholar
• Pozzi, D. et al. REST/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability. EMBO J. 32, 2994–3007 (2013).
  CAS PubMed PubMed Central Google Scholar
• Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, RESEARCH0034 (2002).
  PubMed PubMed Central Google Scholar