Cogprints

Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential

Bauchwitz, Dr. Robert P. (2007) Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. [Preprint]

This is the latest version of this eprint.

Full text available as:

[img] PDF (Min_et_al_2007_FX-GSK3_submitted012908.pdf) - Submitted Version
Restricted to Registered users only

547Kb
[img] PDF (Min_et_al_2007_FX-GSK3_Supplemental_Info_submitted012908.pdf) - Submitted Version
Restricted to Registered users only

125Kb
[img]
Preview
PDF (Min_et.al._FX-GSK3_2008_NP_online.pdf) - Published Version
551Kb
[img]
Preview
PDF (Min_et.al._FX-GSK3_Supplemental_Info_NP_online.pdf) - Published Version
423Kb

Abstract

Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X Syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal mGluR5-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase 3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained active with chronic dosing, although its effects were transient even when given from birth. The combination of mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential.

Item Type:Preprint
Keywords:GSK3, Fragile X Syndrome, mental retardation, lithium, autism
Subjects:Neuroscience > Neuropharmacology
ID Code:5925
Deposited By: Bauchwitz, Robert
Deposited On:10 Feb 2008 03:27
Last Modified:11 Mar 2011 08:57

Available Versions of this Item

References in Article

Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.

Amdisen, A. 1990. Lithium Neurotoxicity - The Reliability of Serum Lithium Measurements. Human Psychopharmacology, 5, 281-285.

Aschrafi, A., Cunningham, B. A., Edelman, G. M., Vanderklish, P. W. 2005. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proceedings of the National Academy of Sciences, 102(6), 2180-2185.

Bachmann, R. F., Schloesser, R. J., Gould, T. D., Manji, H. K. 2005. Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics. Mol Neurobiol, 32(2), 173-202.

Bakker, C. E., Consortium, D.-B. F. X. 1994. Fmr1 knockout mice: a model to study fragile X mental retardation. Cell, 78(1), 23-33.

Bao, W. L., Williams, A. J., Faden, A. I., Tortella, F. C. 2001. Selective mGluR5 receptor antagonist or agonist provides neuroprotection in a rat model of focal cerebral ischemia. . Brain Research, 922, 173-179.

Bardoni, B., Mandel, J.-L. 2002. Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes. Current Opinion in Genetics & Development, 12(3), 284-293.

Bauchwitz, R. P. 2002. Pharmacologic and Genetic Targets in Fragile X Treatment

Research, 8th International Fragile X

Foundation Conference (Vol. K6).

Baumgardner, T. L., Reiss, A. L., Freund, L. S., Abrams, M. T. 1995. Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics, 95(5), 744-752.

Bear, M. F., Dolen, G., Osterweil, E., Nagarajan, N. 2007. Fragile X: Translation in Action. Neuropsychopharmacology, 33(1), 84-87.

Beaulieu, J.-M., Sotnikova, T. D., Yao, W.-D., Kockeritz, L., Woodgett, J. R., Gainetdinov, R. R., Caron, M. G. 2004. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proceedings of the National Academy of Sciences, 101(14), 5099-5104.

Bernard-Helary, K., Lapouble, E., Ardourel, M., Hevor, T., Cloix, J. F. 2000. Correlation between brain glycogen and convulsive state in mice submitted to methionine sulfoximine. Life Sci, 67(14), 1773-1781.

Berridge, M. J., Downes, C. P., Hanley, M. R. 1989. Neural and developmental actions of lithium: a unifying hypothesis. Cell, 59(3), 411-419.

Bersudsky, Y., Shaldubina, A., Belmaker, R. H. 2007. Lithium's effect in forced-swim test is blood level dependent but not dependent on weight loss. Behav Pharmacol, 18(1), 77-80.

Bhat, R., Xue, Y., Berg, S., Hellberg, S., Ormo, M., Nilsson, Y., Radesater, A. C., Jerning, E., Markgren, P. O., Borgegard, T., Nylof, M., Gimenez-Cassina, A., Hernandez, F., Lucas, J. J., Diaz-Nido, J., Avila, J. 2003. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem, 278(46), 45937-45945.

Bregman, J. D., Leckman, J. F., Ort, S. I. 1988. Fragile X syndrome: genetic predisposition to psychopathology. J Autism Dev Disord, 18(3), 343-354.

Brown, A. M. 2004. Brain glycogen re-awakened. Journal of Neurochemistry, 89(3), 537-552.

Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., Darnell, R. B., Warren, S. T. 2001. Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell, 107(4), 477-487.

Cataldo, A. M., Broadwell, R. D. 1986. Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol, 15(4), 511-524.

Chen, L., Toth, M. 2001. Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience, 103(4), 1043-1050.

Cheng, K., Creacy, S., Larner, J. 1983. 'Insulin-like' effects of lithium ion on isolated rat adipocytes. II. Specific activation of glycogen synthase. Mol Cell Biochem, 56(2), 183-189.

Choi, I. Y., Seaquist, E. R., Gruetter, R. 2003. Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res, 72(1), 25-32.

Chuang, S. C., Zhao, W., Bauchwitz, R., Yan, Q., Bianchi, R., Wong, R. K. 2005. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci, 25(35), 8048-8055.

Coghlan, M. P., Culbert, A. A., Cross, D. A., Corcoran, S. L., Yates, J. W., Pearce, N. J., Rausch, O. L., Murphy, G. J., Carter, P. S., Roxbee Cox, L., Mills, D., Brown, M. J., Haigh, D., Ward, R. W., Smith, D. G., Murray, K. J., Reith, A. D., Holder, J. C. 2000. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol, 7(10), 793-803.

Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., Greenough, W. T. 1997. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A, 94(10), 5401-5404.

Correll, C. U. 2007. Weight gain and metabolic effects of mood stabilizers and antipsychotics in pediatric bipolar disorder: a systematic review and pooled analysis of short-term trials. J Am Acad Child Adolesc Psychiatry, 46(6), 687-700.

Daoudal, G., Debanne, D. 2003. Long-Term Plasticity of Intrinsic Excitability: Learning Rules and Mechanisms. Learn. Mem., 10(6), 456-465.

Darnell, J. C., Jensen, K. B., Jin, P., Brown, V., Warren, S. T., Darnell, R. B. 2001. Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell, 107(4), 489-499.

De Sarno, P., Bijur, G. N., Zmijewska, A. A., Li, X., Jope, R. S. 2006. In vivo regulation of GSK3 phosphorylation by cholinergic and NMDA receptors. Neurobiol Aging, 27(3), 413-422.

Doble, B. W., Woodgett, J. R. 2003. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci, 116(7), 1175-1186.

Dockendorff, T. C., Su, H. S., McBride, S. M., Yang, Z., Choi, C. H., Siwicki, K. K., Sehgal, A., Jongens, T. A. 2002. Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron, 34(6), 973-984.

Fisch, G. S., Carpenter, N. J., Holden, J. J., Simensen, R., Howard-Peebles, P. N., Maddalena, A., Pandya, A., Nance, W. 1999. Longitudinal assessment of adaptive and maladaptive behaviors in fragile X males: growth, development, and profiles. Am J Med Genet, 83(4), 257-263.

Garcia-Perez, J., Avila, J., Diaz-Nido, J. 1998. Implication of cyclin-dependent kinases and glycogen synthase kinase 3 in the phosphorylation of microtubule-associated protein 1B in developing neuronal cells. J Neurosci Res, 52(4), 445-452.

Gasparini, F., Lingenhohl, K., Stoehr, N., Flor, P. J., Heinrich, M., Vranesic, I., Biollaz, M., Allgeier, H., Heckendorn, R., Urwyler, S., Varney, M. A., Johnson, E. C., Hess, S. D., Rao, S. P., Sacaan, A. I., Santori, E. M., Velicelebi, G., Kuhn, R. 1999. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology, 38(10), 1493-1503.

Gass, P., Wolfer, D. P., Balschun, D., Rudolph, D., Frey, U., Lipp, H.-P., Schutz, G. 1998. Deficits in Memory Tasks of Mice with CREB Mutations Depend on Gene Dosage. Learn. Mem., 5(4), 274-288.

Gibbs, M. E., Lloyd, H. G., Santa, T., Hertz, L. 2007. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J Neurosci Res, 85(15), 3326-3333.

Gilman, A. G., Goodman, L. S., Gliman, A., Mayer, S. E., Melmon, K. L. 1980. Goodman and Gilman's The Pharmacologic Basis of Therapeutics (6th ed.): Macmillan.

Goni-Oliver, P., Lucas, J. J., Avila, J., Hernandez, F. 2007. N-terminal Cleavage of GSK-3 by Calpain: A NEW FORM OF GSK-3 REGULATION. J. Biol. Chem., 282(31), 22406-22413.

Grace, A. A. 2002. Dopamine. In K. L. Davis, D. Charney, J. T. Coyle andC. Nemeroff (K. L. Davis, D. Charney, J. T. Coyle andC. Nemeroff(K. L. Davis, D. Charney, J. T. Coyle andC. Nemeroffs.), Neuropsychopharmacolgy: The Fifth Generation of Progress: American College of Neuropsychopharmacology.

Grimes, C. A., Jope, R. S. 2001. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem, 78(6), 1219-1232.

Grossman, A. W., Aldridge, G. M., Weiler, I. J., Greenough, W. T. 2006. Local Protein Synthesis and Spine Morphogenesis: Fragile X Syndrome and Beyond. Journal of Neuroscience, 26(27), 7151-7155.

Gruss, M., Braun, K. 2004. Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice. Neurochem Int, 45(1), 81-88.

Hayashi, M. L., Rao, B. S., Seo, J. S., Choi, H. S., Dolan, B. M., Choi, S. Y., Chattarji, S., Tonegawa, S. 2007. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A, 104(27), 11489-11494.

Hinton, V. J., Brown, W. T., Wisniewski, K., Rudelli, R. D. 1991. Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet, 41(3), 289-294.

Hooper, C., Markevich, V., Plattner, F., Killick, R., Schofield, E., Engel, T., Hernandez, F., Anderton, B., Rosenblum, K., Bliss, T., Cooke, S. F., Avila, J., Lucas, J. J., Giese, K. P., Stephenson, J., Lovestone, S. 2007. Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur J Neurosci, 25(1), 81-86.

Huber, K. M., Gallagher, S. M., Warren, S. T., Bear, M. F. 2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A, 99(11), 7746-7750.

Hummel, T., Krukkert, K., Roos, J., Davis, G., Klambt, C. 2000. Drosophila Futsch/22C10 is a MAP1B-like protein required for dendritic and axonal development. Neuron, 26(2), 357-370.

Jope, R. S., Johnson, G. V. 2004. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci, 29(2), 95-102.

Kallen, B., Tandberg, A. 1983. Lithium and pregnancy. A cohort study on manic-depressive women. Acta Psychiatr Scand, 68(2), 134-139.

Kim, D. H., Jung, J. S., Song, D. K., Suh, H. W., Huh, S. O., Kim, Y. H. 1998. Intracerebroventricular injection-induced increase in plasma corticosterone levels in the mouse: a stress model. J Pharmacol Toxicol Methods, 39(2), 71-73.

Kimball, S. R. 1999. Eukaryotic initiation factor eIF2. Int J Biochem Cell Biol, 31(1), 25-29.

Klein, P. S., Melton, D. A. 1996. A molecular mechanism for the effect of lithium onā€ development. Proceedings of the National Academy of Sciences, 93(16), 8455-8459.

Kozikowski, A. P., Gaisina, I. N., Petukhov, P. A., Sridhar, J., King, L. T., Blond, S. Y., Duka, T., Rusnak, M., Sidhu, A. 2006. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease. ChemMedChem, 1(2), 256-266.

Laggerbauer, B., Ostareck, D., Keidel, E., Ostareck-Lederer, A., Fischer, U. 2001. Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum Mol Genet, 10(4), 329-338.

Lea, P. M. t., Movsesyan, V. A., Faden, A. I. 2005. Neuroprotective activity of the mGluR5 antagonists MPEP and MTEP against acute excitotoxicity differs and does not reflect actions at mGluR5 receptors. Br J Pharmacol, 145(4), 527-534.

Li, Z., Zhang, Y., Ku, L., Wilkinson, K. D., Warren, S. T., Feng, Y. 2001. The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res, 29(11), 2276-2283.

Linden, S., Rich, C. L. 1983. The use of lithium during pregnancy and lactation. J Clin Psychiatry, 44(10), 358-361.

Lucas, F. R., Goold, R. G., Gordon-Weeks, P. R., Salinas, P. C. 1998. Inhibition of GSK-3beta leading to the loss of phosphorylated MAP-1B is an early event in axonal remodelling induced by WNT-7a or lithium. J Cell Sci, 111 ( Pt 10), 1351-1361.

Magistretti, P. J. 2006. Neuron-glia metabolic coupling and plasticity. J Exp Biol, 209(12), 2304-2311.

Magistretti, P. J., Pellerin, L., Martin, J. L. 2000. Brain Energy Metabolism. In Neuropsychopharmacology: The Fourth Generation of Progress: American College of Neuropsychopharmacology.

Martinez, A., Castro, A., Dorronsoro, I., Alonso, M. 2002. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev, 22(4), 373-384.

McBride, S. M., Choi, C. H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., McDonald, T. V., Jongens, T. A. 2005. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron, 45(5), 753-764.

Meeker, D., Kim, J. H., Vezina, P. 1998. Depletion of dopamine in the nucleus accumbens prevents the generation of locomotion by metabotropic glutamate receptor activation. Brain Res, 812(1-2), 260-264.

Messiha, F. S. 1986. Lithium and the neonate: developmental and metabolic aspects. Alcohol, 3(2), 107-112.

Messiha, F. S. 1993. Maternally-mediated developmental lithium toxicity in the mouse. Gen Pharmacol, 24(1), 9-15.

Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T., Eberwine, J. 2003. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron, 37(3), 417-431.

Musumeci, S. A., Bosco, P., Calabrese, G., Bakker, C., De Sarro, G. B., Elia, M., Ferri, R., Oostra, B. A. 2000. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia, 41(1), 19-23.

Musumeci, S. A., Hagerman, R. J., Ferri, R., Bosco, P., Dalla Bernardina, B., Tassinari, C. A., De Sarro, G. B., Elia, M. 1999. Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia, 40(8), 1092-1099.

O'Brien, W. T., Harper, A. D., Jove, F., Woodgett, J. R., Maretto, S., Piccolo, S., Klein, P. S. 2004. Glycogen Synthase Kinase-3{beta} Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium. J. Neurosci., 24(30), 6791-6798.

O'Dowd, B. S., Gibbs, M. E., Ng, K. T., Hertz, E., Hertz, L. 1994. Astrocytic glycogenolysis energizes memory processes in neonate chicks. Brain Res Dev Brain Res, 78(1), 137-141.

Peier, A. M., McIlwain, K. L., Kenneson, A., Warren, S. T., Paylor, R., Nelson, D. L. 2000. (Over)correction of FMR1 deficiency with YAC transgenics: behavioral and physical features. Hum Mol Genet, 9(8), 1145-1159.

Peineau, S., Taghibiglou, C., Bradley, C., Wong, T. P., Liu, L., Lu, J., Lo, E., Wu, D., Saule, E., Bouschet, T., Matthews, P., Isaac, J. T., Bortolotto, Z. A., Wang, Y. T., Collingridge, G. L. 2007. LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron, 53(5), 703-717.

Pilc, A., Klodzinska, A., Branski, P., Nowak, G., Palucha, A., Szewczyk, B., Tatarczynska, E., Chojnacka-Wojcik, E., Wieronska, J. M. 2002. Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats. Neuropharmacology, 43(2), 181-187.

Pintor, A., Potenza, R. L., Domenici, M. R., Tiburzi, F., Reggio, R., Pezzola, A., Popoli, P. 2000. Age-related decline in the functional response of striatal group I mGlu receptors. Neuroreport, 11(13), 3033-3038.

Popoli, P., Pintor, A., Tebano, M. T., Frank, C., Pepponi, R., Nazzicone, V., Grieco, R., Pezzola, A., Reggio, R., Minghetti, L., De Berardinis, M. A., Martire, A., Potenza, R. L., Domenici, M. R., Massotti, M. 2004. Neuroprotective effects of the mGlu5R antagonist MPEP towards quinolinic acid-induced striatal toxicity: involvement of pre- and post-synaptic mechanisms and lack of direct NMDA blocking activity. Journal of Neurochemistry, 89(6), 1479-1489.

Qin, M., Kang, J., Smith, C. B. 2002. Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A, 99(24), 15758-15763.

Quevedo, C., Alcazar, A., Salinas, M. 2000. Two different signal transduction pathways are implicated in the regulation of initiation factor 2B activity in insulin-like growth factor-1-stimulated neuronal cells. J Biol Chem, 275(25), 19192-19197.

Sayas, C. L., Avila, J., Wandosell, F. 2002. Glycogen Synthase Kinase-3 Is Activated in Neuronal Cells by Galpha 12 and Galpha 13 by Rho-Independent and Rho-Dependent Mechanisms. J. Neurosci., 22(16), 6863-6875.

Schachtman, T. R., Bills, C., Ghinescu, R., Murch, K., Serfozo, P., Simonyi, A. 2003. MPEP, a selective metabotropic glutamate receptor 5 antagonist, attenuates conditioned taste aversion in rats. Behav Brain Res, 141(2), 177-182.

Schaeffer, C., Bardoni, B., Mandel, J. L., Ehresmann, B., Ehresmann, C., Moine, H. 2001. The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. Embo J, 20(17), 4803-4813.

Schapiro, M. B., Murphy, D. G., Hagerman, R. J., Azari, N. P., Alexander, G. E., Miezejeski, C. M., Hinton, V. J., Horwitz, B., Haxby, J. V., Kumar, A., et al. 1995. Adult fragile X syndrome: neuropsychology, brain anatomy, and metabolism. Am J Med Genet, 60(6), 480-493.

Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.-L., Giangrande, A. 2003. CYFIP/Sra-1 Controls Neuronal Connectivity in Drosophila and Links the Rac1 GTPase Pathway to the Fragile X Protein. Neuron, 38(6), 887-898.

Stambolic, V., Ruel, L., Woodgett, J. R. 1996. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol, 6(12), 1664-1668.

Su, Y., Ryder, J., Li, B., Wu, X., Fox, N., Solenberg, P., Brune, K., Paul, S., Zhou, Y., Liu, F., Ni, B. 2004. Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry, 43(22), 6899-6908.

Takahashi, M., Tomizawa, K., Kato, R., Sato, K., Uchida, T., Fujita, S. C., Imahori, K. 1994. Localization and developmental changes of tau protein kinase I/glycogen synthase kinase-3 beta in rat brain. J Neurochem, 63(1), 245-255.

Timmer, R. T., Sands, J. M. 1999. Lithium intoxication. J Am Soc Nephrol, 10(3), 666-674.

Tucker, B., Richards, R. I., Lardelli, M. 2006. Contribution of mGluR and Fmr1 functional pathways to neurite morphogenesis, craniofacial development and fragile X syndrome. Hum Mol Genet, 15(23), 3446-3458.

Vasdev, N., Garcia, A., Stableford, W. T., Young, A. B., Meyer, J. H., Houle, S., Wilson, A. A. 2005. Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): a radiolabelled glycogen synthase kinase-3beta specific inhibitor for PET studies. Bioorg Med Chem Lett, 15(23), 5270-5273.

Volk, L. J., Pfeiffer, B. E., Gibson, J. R., Huber, K. M. 2007. Multiple Gq-Coupled Receptors Converge on a Common Protein Synthesis-Dependent Long-Term Depression That Is Affected in Fragile X Syndrome Mental Retardation. J. Neurosci., 27(43), 11624-11634.

Wagman, A. S., Johnson, K. W., Bussiere, D. E. 2004. Discovery and development of GSK3 inhibitors for the treatment of type 2 diabetes. Curr Pharm Des, 10(10), 1105-1137.

Weiler, I. J., Irwin, S. A., Klintsova, A. Y., Spencer, C. M., Brazelton, A. D., Miyashiro, K., Comery, T. A., Patel, B., Eberwine, J., Greenough, W. T. 1997. Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc Natl Acad Sci U S A, 94(10), 5395-5400.

Wiesinger, H., Hamprecht, B., Dringen, R. 1997. Metabolic pathways for glucose in astrocytes. Glia, 21(1), 22-34.

Woodgett, J. R. 1990. Molecular cloning and expression of glycogen synthase kinase-3/factor A. Embo J, 9(8), 2431-2438.

Yan, Q. J., Asafo-Adjei, P. K., Arnold, H. M., Brown, R. E., Bauchwitz, R. P. 2004. A phenotypic and molecular characterization of the fmr1-tm1Cgr Fragile X mouse. Genes Brain Behav, 3(6), 337-359.

Yan, Q. J., Rammal, M., Tranfaglia, M., Bauchwitz, R. P. 2005. Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology, 49(7), 1053-1066.

Yan, Q. J., Sikorski, C., Bauchwitz, R. P. 2005. GSK3 inhibitors revert Fragile X mouse audiogenic seizure and open field exploratory behaviors to wild type. Society for Neuroscience Abstracts, 679.11.

Zhang, Y. Q., Bailey, A. M., Matthies, H. J., Renden, R. B., Smith, M. A., Speese, S. D., Rubin, G. M., Broadie, K. 2001. Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell, 107(5), 591-603.

Zhang, Y. Q., Friedman, D. B., Wang, Z., Woodruff, E., III, Pan, L., O'Donnell, J., Broadie, K. 2005. Protein Expression Profiling of the Drosophila Fragile X Mutant Brain Reveals Up-regulation of Monoamine Synthesis. Mol Cell Proteomics, 4(3), 278-290.

Zhou, R., Gray, N. A., Yuan, P., Li, X., Chen, J., Chen, G., Damschroder-Williams, P., Du, J., Zhang, L., Manji, H. K. 2005. The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers. J Neurosci, 25(18), 4493-4502.

Zhu, L. Q., Wang, S. H., Liu, D., Yin, Y. Y., Tian, Q., Wang, X. C., Wang, Q., Chen, J. G., Wang, J. Z. 2007. Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments. J Neurosci, 27(45), 12211-12220.

Metadata

Repository Staff Only: item control page