Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2017

Open Access 01-12-2017 | Research

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety

Authors: Tori L. Schaefer, Matthew H. Davenport, Lindsay M. Grainger, Chandler K. Robinson, Anthony T. Earnheart, Melinda S. Stegman, Anna L. Lang, Amy A. Ashworth, Gemma Molinaro, Kimberly M. Huber, Craig A. Erickson

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2017

Login to get access

Abstract

Background

Fragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/inhibitory signaling balance, leading to increased neuronal hyperexcitability and altered behavior. Acamprosate (the calcium salt of N-acetylhomotaurinate), a drug FDA-approved for relapse prevention in the treatment of alcohol dependence in adults, is a novel agent with multiple mechanisms that may be beneficial for people with FXS. There are questions regarding the neuroactive effects of acamprosate and the significance of the molecule’s calcium moiety. Therefore, the electrophysiological, cellular, molecular, and behavioral effects of acamprosate were assessed in the Fmr1 -/y (knock out; KO) mouse model of FXS controlling for the calcium salt in several experiments.

Methods

Fmr1 KO mice and their wild-type (WT) littermates were utilized to assess acamprosate treatment on cortical UP state parameters, dendritic spine density, and seizure susceptibility. Brain extracellular-signal regulated kinase 1/2 (ERK1/2) activation was used to investigate this signaling molecule as a potential biomarker for treatment response. Additional adult mice were used to assess chronic acamprosate treatment and any potential effects of the calcium moiety using CaCl2 treatment on behavior and nuclear ERK1/2 activation.

Results

Acamprosate attenuated prolonged cortical UP state duration, decreased elevated ERK1/2 activation in brain tissue, and reduced nuclear ERK1/2 activation in the dentate gyrus in KO mice. Acamprosate treatment modified behavior in anxiety and locomotor tests in Fmr1 KO mice in which control-treated KO mice were shown to deviate from control-treated WT mice. Mice treated with CaCl2 were not different from saline-treated mice in the adult behavior battery or nuclear ERK1/2 activation.

Conclusions

These data indicate that acamprosate, and not calcium, improves function reminiscent of reduced anxiety-like behavior and hyperactivity in Fmr1 KO mice and that acamprosate attenuates select electrophysiological and molecular dysregulation that may play a role in the pathophysiology of FXS. Differences between control-treated KO and WT mice were not evident in a recognition memory test or in examination of acoustic startle response/prepulse inhibition which impeded conclusions from being made about the treatment effects of acamprosate in these instances.
Appendix
Available only for authorised users
Literature
1.
Turner G, Webb T, Wake S, Robinson H. Prevalence of fragile X syndrome. Am J Med Genet. 1996;64(1):196–7.PubMedCrossRef
2.
Song FJ, Barton P, Sleightholme V, Yao GL, Fry-Smith A. Screening for fragile X syndrome: a literature review and modelling study. Health Technol Assess. 2003;7(16):1–106.CrossRef
3.
4.
Tsiouris JA, Brown WT. Neuropsychiatric symptoms of fragile X syndrome: pathophysiology and pharmacotherapy. CNS Drugs. 2004;18(11):687–703.PubMedCrossRef
5.
Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, Kronk R, Delahunty C, Hessl D, Visootsak J, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123(1):378–90.PubMedPubMedCentralCrossRef
6.
Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci. 2004;27(7):370–7.PubMedCrossRef
7.
Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, Bear MF, Lindemann L. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron. 2012;74(1):49–56.PubMedCrossRef
8.
Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP. Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology. 2005;49(7):1053–66.PubMedCrossRef
9.
10.
Thomas AM, Bui N, Graham D, Perkins JR, Yuva-Paylor LA, Paylor R. Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome. Behav Brain Res. 2011;223(2):310–21.PubMedPubMedCentralCrossRef
11.
Olmos-Serrano JL, Paluszkiewicz SM, Martin BS, Kaufmann WE, Corbin JG, Huntsman MM. Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome. J Neurosci. 2010;30(29):9929–38.PubMedPubMedCentralCrossRef
12.
El Idrissi A, Yan X, L’Amoreaux W, Brown WT, Dobkin C. Neuroendocrine alterations in the fragile X mouse. Results Probl Cell Differ. 2012;54:201–21.PubMedCrossRef
13.
D'Hulst C, Heulens I, Brouwer JR, Willemsen R, De Geest N, Reeve SP, De Deyn PP, Hassan BA, Kooy RF. Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS). Brain Res. 2009;1253:176–83.PubMedCrossRef
14.
D'Hulst C, De Geest N, Reeve SP, Van Dam D, De Deyn PP, Hassan BA, Kooy RF. Decreased expression of the GABAA receptor in fragile X syndrome. Brain Res. 2006;1121(1):238–45.PubMedCrossRef
15.
El Idrissi A, Ding XH, Scalia J, Trenkner E, Brown WT, Dobkin C. Decreased GABA(A) receptor expression in the seizure-prone fragile X mouse. Neurosci Lett. 2005;377(3):141–6.PubMedCrossRef
16.
Rudelli RD, Brown WT, Wisniewski K, Jenkins EC, Laure-Kamionowska M, Connell F, Wisniewski HM. Adult fragile X syndrome. Clinico-neuropathologic findings. Acta Neuropathol. 1985;67(3–4):289–95.PubMedCrossRef
17.
Hinton VJ, Brown WT, Wisniewski K, Rudelli RD. Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet. 1991;41(3):289–94.PubMedCrossRef
18.
Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, Kooy F, Willems PJ, Cras P, Kozlowski PB, et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet. 2001;98(2):161–7.PubMedCrossRef
19.
Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, Greenough WT. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A. 1997;94(10):5401–4.PubMedPubMedCentralCrossRef
20.
Galvez R, Greenough WT. Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am J Med Genet A. 2005;135(2):155–60.PubMedCrossRef
21.
McKinney BC, Grossman AW, Elisseou NM, Greenough WT. Dendritic spine abnormalities in the occipital cortex of C57BL/6 Fmr1 knockout mice. Am J Med Genet B Neuropsychiatr Genet. 2005;136B(1):98–102.PubMedCrossRef
22.
Su T, Fan HX, Jiang T, Sun WW, Den WY, Gao MM, Chen SQ, Zhao QH, Yi YH. Early continuous inhibition of group 1 mGlu signaling partially rescues dendritic spine abnormalities in the Fmr1 knockout mouse model for fragile X syndrome. Psychopharmacology (Berl). 2011;215(2):291–300.CrossRef
23.
Hayashi ML, Rao BS, Seo JS, Choi HS, Dolan BM, Choi SY, Chattarji S, Tonegawa S. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A. 2007;104(27):11489–94.PubMedPubMedCentralCrossRef
24.
Gibson JR, Bartley AF, Hays SA, Huber KM. Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J Neurophysiol. 2008;100(5):2615–26.PubMedPubMedCentralCrossRef
25.
Hays SA, Huber KM, Gibson JR. Altered neocortical rhythmic activity states in Fmr1 KO mice are due to enhanced mGluR5 signaling and involve changes in excitatory circuitry. J Neurosci. 2011;31(40):14223–34.PubMedPubMedCentralCrossRef
26.
Ding Q, Sethna F, Wang H. Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background. Behav Brain Res. 2014;271:72–8.PubMedCrossRef
27.
Sweatt JD. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol. 2004;14(3):311–7.PubMedCrossRef
28.
29.
Samuels IS, Karlo JC, Faruzzi AN, Pickering K, Herrup K, Sweatt JD, Saitta SC, Landreth GE. Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci. 2008;28(27):6983–95.PubMedPubMedCentralCrossRef
30.
Kelleher 3rd RJ, Govindarajan A, Jung HY, Kang H, Tonegawa S. Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell. 2004;116(3):467–79.PubMedCrossRef
31.
Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell. 2008;135(3):549–60.PubMedPubMedCentralCrossRef
32.
Busca R, Christen R, Lovern M, Clifford AM, Yue JX, Goss GG, Pouyssegur J, Lenormand P. ERK1 and ERK2 present functional redundancy in tetrapods despite higher evolution rate of ERK1. BMC Evol Biol. 2015;15:179.PubMedPubMedCentralCrossRef
33.
Robbins DJ, Zhen E, Owaki H, Vanderbilt CA, Ebert D, Geppert TD, Cobb MH. Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. J Biol Chem. 1993;268(7):5097–106.PubMed
34.
Lefloch R, Pouyssegur J, Lenormand P. Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels. Mol Cell Biol. 2008;28(1):511–27.PubMedCrossRef
35.
Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs. Oncogene. 2007;26(22):3100–12.PubMedCrossRef
36.
de Esch CE, van den Berg WE, Buijsen RA, Jaafar IA, Nieuwenhuizen-Bakker IM, Gasparini F, Kushner SA, Willemsen R. Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test. Neurobiol Dis. 2015;75C:31–9.CrossRef
37.
Deacon RM, Glass L, Snape M, Hurley MJ, Altimiras FJ, Biekofsky RR, Cogram P. NNZ-2566, a novel analog of (1–3) IGF-1, as a potential therapeutic agent for fragile X syndrome. Neruomol Med. 2015;17(1):71–82.CrossRef
38.
Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, Weiler IJ, Greenough WT. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr. 2008;29(4):293–302.PubMedCrossRef
39.
Wang X, Snape M, Klann E, Stone JG, Singh A, Petersen RB, Castellani RJ, Casadesus G, Smith MA, Zhu X. Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome. J Neurochem. 2012;121(4):672–9.PubMedCrossRef
40.
Erickson CA, Ray B, Maloney B, Wink LK, Bowers K, Schaefer TL, McDougle CJ, Sokol DK, Lahiri DK. Impact of acamprosate on plasma amyloid-beta precursor protein in youth: a pilot analysis in fragile X syndrome-associated and idiopathic autism spectrum disorder suggests a pharmacodynamic protein marker. J Psychiatr Res. 2014;59:220–8.PubMedPubMedCentralCrossRef
41.
Erickson CA, Wink LK, Ray B, Early MC, Stiegelmeyer E, Mathieu-Frasier L, Patrick V, Lahiri DK, McDougle CJ. Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology. 2013;228(1):75–84.PubMedCrossRef
42.
Venezia V, Nizzari M, Repetto E, Violani E, Corsaro A, Thellung S, Villa V, Carlo P, Schettini G, Florio T, et al. Amyloid precursor protein modulates ERK-1 and −2 signaling. Ann N Y Acad Sci. 2006;1090:455–65.PubMedCrossRef
43.
Nizzari M, Venezia V, Repetto E, Caorsi V, Magrassi R, Gagliani MC, Carlo P, Florio T, Schettini G, Tacchetti C, et al. Amyloid precursor protein and Presenilin1 interact with the adaptor GRB2 and modulate ERK 1,2 signaling. J Biol Chem. 2007;282(18):13833–44.PubMedCrossRef
44.
Han BH, Holtzman DM. BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway. J Neurosci. 2000;20(15):5775–81.PubMed
45.
Yamagata Y, Kaneko K, Kase D, Ishihara H, Nairn AC, Obata K, Imoto K. Regulation of ERK1/2 mitogen-activated protein kinase by NMDA-receptor-induced seizure activity in cortical slices. Brain Res. 2013;1507:1–10.PubMedPubMedCentralCrossRef
46.
Merlo D, Cifelli P, Cicconi S, Tancredi V, Avoli M. 4-Aminopyridine-induced epileptogenesis depends on activation of mitogen-activated protein kinase ERK. J Neurochem. 2004;89(3):654–9.PubMedCrossRef
47.
Schaefer TL, Davenport MH, Erickson CA. Emerging pharmacologic treatment options for fragile X syndrome. Appl Clin Genet. 2015;8:75–93.PubMedPubMedCentral
48.
49.
Novartis discontinues development of mavoglurant (AFQ056) for fragile X syndrome
50.
Berry-Kravis E, Krause SE, Block SS, Guter S, Wuu J, Leurgans S, Decle P, Potanos K, Cook E, Salt J, et al. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol. 2006;16(5):525–40.PubMedCrossRef
51.
Hinton DJ, Lee MR, Jacobson TL, Mishra PK, Frye MA, Mrazek DA, Macura SI, Choi DS. Ethanol withdrawal-induced brain metabolites and the pharmacological effects of acamprosate in mice lacking ENT1. Neuropharmacology. 2012;62(8):2480–8.PubMedPubMedCentralCrossRef
52.
Dahchour A, De Witte P. Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods. Alcohol Clin Exp Res. 2003;27(3):465–70.PubMedCrossRef
53.
Spanagel R, Vengeliene V, Jandeleit B, Fischer WN, Grindstaff K, Zhang X, Gallop MA, Krstew EV, Lawrence AJ, Kiefer F. Acamprosate produces its anti-relapse effects via calcium. Neuropsychopharmacology. 2014;39(4):783–91.PubMedPubMedCentralCrossRef
54.
al Qatari M, Bouchenafa O, Littleton J. Mechanism of action of acamprosate. Part II. Ethanol dependence modifies effects of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex. Alcohol Clin Exp Res. 1998;22(4):810–4.PubMedCrossRef
55.
Dahchour A, De Witte P, Bolo N, Nedelec JF, Muzet M, Durbin P, Macher JP. Central effects of acamprosate: part 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats. Psychiatry Res. 1998;82(2):107–14.PubMedCrossRef
56.
Harris BR, Prendergast MA, Gibson DA, Rogers DT, Blanchard JA, Holley RC, Fu MC, Hart SR, Pedigo NW, Littleton JM. Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol Clin Exp Res. 2002;26(12):1779–93.PubMedCrossRef
57.
Mayer S, Harris B, Gibson DA, Blanchard J, Prendergast MA, Holley RC, Littleton J. Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced by spermidine or by changing the medium in organotypic hippocampal slice cultures from rat. Alcohol Clin Exp Res. 2002;26(5):655–62.PubMedCrossRef
58.
Nalpas B, Dabadie H, Parot P, Paccalin J. Acamprosate. From pharmacology to therapeutics. Encéphale. 1990;16(3):175–9.PubMed
59.
Palucha-Poniewiera A, Pilc A. Involvement of mGlu5 and NMDA receptors in the antidepressant-like effect of acamprosate in the tail suspension test. Prog Neuro-Psychopharmacol Biol Psychiatry. 2012;39(1):102–6.CrossRef
60.
Erickson CA, Mullett JE, McDougle CJ. Brief report: acamprosate in fragile X syndrome. J Autism Dev Disord. 2010;40(11):1412–6.PubMedCrossRef
61.
62.
Mann K, Hoffmann S, Pawlak CR. Does acamprosate really produce its anti-relapse effects via calcium? No support from the PREDICT study in human alcoholics. Neuropsychopharmacology. 2016;41(3):659–60.PubMedPubMedCentralCrossRef
63.
Spanagel R, Vengeliene V, Kiefer F. Reply to: Does acamprosate really produce its anti-relapse effects via calcium? No support from the PREDICT study in human alcoholics. Neuropsychopharmacology. 2016;41(3):661–2.PubMedPubMedCentralCrossRef
64.
Ronesi JA, Collins KA, Hays SA, Tsai NP, Guo W, Birnbaum SG, Hu JH, Worley PF, Gibson JR, Huber KM. Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci. 2012;15(3):431–40. S431.PubMedPubMedCentralCrossRef
65.
Sanchez-Vives MV, McCormick DA. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci. 2000;3(10):1027–34.PubMedCrossRef
66.
Agmon A, Connors BW. Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. Neuroscience. 1991;41(2–3):365–79.PubMedCrossRef
67.
Mientjes EJ, Nieuwenhuizen I, Kirkpatrick L, Zu T, Hoogeveen-Westerveld M, Severijnen L, Rife M, Willemsen R, Nelson DL, Oostra BA. The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo. Neurobiol Dis. 2006;21(3):549–55.PubMedCrossRef
68.
Musumeci SA, Bosco P, Calabrese G, Bakker C, De Sarro GB, Elia M, Ferri R, Oostra BA. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia. 2000;41(1):19–23.PubMedCrossRef
69.
Engelhard K, Werner C, Lu H, Mollenberg O, Zieglgansberger W, Kochs E. The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e. Anaesthesist. 2000;49(9):816–21.PubMedCrossRef
70.
Czachowski CL, Delory MJ. Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats. Psychopharmacology (Berl). 2009;204(2):335–48.CrossRef
71.
Schaefer TL, Vorhees CV, Williams MT. Mouse plasmacytoma-expressed transcript 1 knock out induced 5-HT disruption results in a lack of cognitive deficits and an anxiety phenotype complicated by hypoactivity and defensiveness. Neuroscience. 2009;164(4):1431–43.PubMedPubMedCentralCrossRef
72.
Schaefer TL, Lingrel JB, Moseley AE, Vorhees CV, Williams MT. Targeted mutations in the Na, K-ATPase alpha 2 isoform confer ouabain resistance and result in abnormal behavior in mice. Synapse. 2011;65(6):520–31.PubMedCrossRef
73.
Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001;125(1–2):279–84.PubMedCrossRef
74.
Liu ZH, Huang T, Smith CB. Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome. Neurobiol Dis. 2012;45(3):1145–52.PubMedCrossRef
75.
Erickson CA, Weng N, Weiler IJ, Greenough WT, Stigler KA, Wink LK, McDougle CJ. Open-label riluzole in fragile X syndrome. Brain Res. 2011;1380:264–70.PubMedCrossRef
76.
Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res. 1988;31(1):47–59.PubMedCrossRef
77.
Frankland PW, Wang Y, Rosner B, Shimizu T, Balleine BW, Dykens EM, Ornitz EM, Silva AJ. Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol Psychiatry. 2004;9(4):417–25.PubMedCrossRef
78.
Hessl D, Berry-Kravis E, Cordeiro L, Yuhas J, Ornitz EM, Campbell A, Chruscinski E, Hervey C, Long JM, Hagerman RJ. Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(4):545–53.PubMedPubMedCentralCrossRef
79.
Tessier CR, Broadie K. The fragile X mental retardation protein developmentally regulates the strength and fidelity of calcium signaling in Drosophila mushroom body neurons. Neurobiol Dis. 2011;41(1):147–59.PubMedCrossRef
80.
Wang H, Fukushima H, Kida S, Zhuo M. Ca2+/calmodulin-dependent protein kinase IV links group I metabotropic glutamate receptors to fragile X mental retardation protein in cingulate cortex. J Biol Chem. 2009;284(28):18953–62.PubMedPubMedCentralCrossRef
81.
Chen L, Yun SW, Seto J, Liu W, Toth M. The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences. Neuroscience. 2003;120(4):1005–17.PubMedCrossRef
82.
Doll CA, Broadie K. Neuron class-specific requirements for fragile X mental retardation protein in critical period development of calcium signaling in learning and memory circuitry. Neurobiol Dis. 2016;89:76–87.PubMedPubMedCentralCrossRef
83.
Chabenat C, Chretien P, Daoust M, Moore N, Andre D, Lhuintre JP, Saligaut C, Boucly P, Boismare F. Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate. Methods Find Exp Clin Pharmacol. 1988;10(5):311–7.PubMed
84.
Long W, Weiss W, Stein SC. Local pain from intramuscular injection of streptomycin calcium chloride complex. J Am Med Assoc. 1953;152(1):25–6.PubMedCrossRef
85.
86.
Sanchez-Vives MV, Mattia M, Compte A, Perez-Zabalza M, Winograd M, Descalzo VF, Reig R. Inhibitory modulation of cortical Up states. J Neurophysiol. 2010;104(3):1314–24.PubMedCrossRef
87.
Guo W, Molinaro G, Collins KA, Hays SA, Paylor R, Worley PF, Szumlinski KK, Huber KM. Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice. J Neurosci. 2016;36(7):2131–47.PubMedPubMedCentralCrossRef
88.
Berton F, Francesconi WG, Madamba SG, Zieglgansberger W, Siggins GR. Acamprosate enhances N-methyl-D-apartate receptor-mediated neurotransmission but inhibits presynaptic GABA(B) receptors in nucleus accumbens neurons. Alcohol Clin Exp Res. 1998;22(1):183–91.PubMedCrossRef
89.
Daoust M, Legrand E, Gewiss M, Heidbreder C, DeWitte P, Tran G, Durbin P. Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats. Pharmacol Biochem Behav. 1992;41(4):669–74.PubMedCrossRef
90.
Madamba SG, Schweitzer P, Zieglgansberger W, Siggins GR. Acamprosate (calcium acetylhomotaurinate) enhances the N-methyl-D-aspartate component of excitatory neurotransmission in rat hippocampal CA1 neurons in vitro. Alcohol Clin Exp Res. 1996;20(4):651–8.PubMedCrossRef
91.
Pierrefiche O, Daoust M, Naassila M. Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network. Neuropharmacology. 2004;47(1):35–45.PubMedCrossRef
92.
Ruby K, Falvey K, Kulesza RJ. Abnormal neuronal morphology and neurochemistry in the auditory brainstem of Fmr1 knockout rats. Neuroscience. 2015;303:285–98.PubMedCrossRef
93.
Rotschafer S, Razak K. Altered auditory processing in a mouse model of fragile X syndrome. Brain Res. 2013;1506:12–24.PubMedCrossRef
94.
Kim H, Gibboni R, Kirkhart C, Bao S. Impaired critical period plasticity in primary auditory cortex of fragile X model mice. J Neurosci. 2013;33(40):15686–92.PubMedPubMedCentralCrossRef
95.
Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci. 2004;5(3):173–83.PubMedCrossRef
96.
Herry C, Trifilieff P, Micheau J, Luthi A, Mons N. Extinction of auditory fear conditioning requires MAPK/ERK activation in the basolateral amygdala. Eur J Neurosci. 2006;24(1):261–9.PubMedCrossRef
97.
Schafe GE, Atkins CM, Swank MW, Bauer EP, Sweatt JD, LeDoux JE. Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning. J Neurosci. 2000;20(21):8177–87.PubMed
98.
Bodai L, Marsh JL. A novel target for Huntington’s disease: ERK at the crossroads of signaling. The ERK signaling pathway is implicated in Huntington's disease and its upregulation ameliorates pathology. Bioessays. 2012;34(2):142–8.PubMedPubMedCentralCrossRef
99.
Kalkman HO. Potential opposite roles of the extracellular signal-regulated kinase (ERK) pathway in autism spectrum and bipolar disorders. Neurosci Biobehav Rev. 2012;36(10):2206–13.PubMedCrossRef
100.
Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993;72(2):269–78.PubMedCrossRef
101.
Weng N, Weiler IJ, Sumis A, Berry-Kravis E, Greenough WT. Early-phase ERK activation as a biomarker for metabolic status in fragile X syndrome. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(7):1253–7.PubMedCrossRef
102.
Satoh Y, Endo S, Nakata T, Kobayashi Y, Yamada K, Ikeda T, Takeuchi A, Hiramoto T, Watanabe Y, Kazama T. ERK2 contributes to the control of social behaviors in mice. J Neurosci. 2011;31(33):11953–67.PubMedCrossRef
103.
Kumar RA, Marshall CR, Badner JA, Babatz TD, Mukamel Z, Aldinger KA, Sudi J, Brune CW, Goh G, Karamohamed S, et al. Association and mutation analyses of 16p11.2 autism candidate genes. PLoS One. 2009;4(2):e4582.PubMedPubMedCentralCrossRef
104.
Vorstman JA, Morcus ME, Duijff SN, Klaassen PW, Heineman-de Boer JA, Beemer FA, Swaab H, Kahn RS, van Engeland H. The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry. 2006;45(9):1104–13.PubMedCrossRef
105.
Mukaddes NM, Herguner S. Autistic disorder and 22q11.2 duplication. World J Biol Psychiatry. 2007;8(2):127–30.PubMedCrossRef
106.
Yang K, Sheikh AM, Malik M, Wen G, Zou H, Brown WT, Li X. Upregulation of Ras/Raf/ERK1/2 signaling and ERK5 in the brain of autistic subjects. Genes Brain Behav. 2011;10(8):834–43.PubMedCrossRef
107.
Sanna PP, Simpson C, Lutjens R, Koob G. ERK regulation in chronic ethanol exposure and withdrawal. Brain Res. 2002;948(1–2):186–91.PubMedCrossRef
108.
Kim SH, Markham JA, Weiler IJ, Greenough WT. Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proc Natl Acad Sci U S A. 2008;105(11):4429–34.PubMedPubMedCentralCrossRef
109.
Backes M, Genc B, Schreck J, Doerfler W, Lehmkuhl G, von Gontard A. Cognitive and behavioral profile of fragile X boys: correlations to molecular data. Am J Med Genet. 2000;95(2):150–6.PubMedCrossRef
110.
Levitas A. Neuropsychiatric aspects of fragile X syndrome. Semin Clin Neuropsychiatry. 1996;1(2):154–67.PubMed
111.
Liu ZH, Chuang DM, Smith CB. Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome. Int J Neuropsychopharmacol. 2011;14(5):618–30.PubMedCrossRef
112.
Koltunowska D, Gibula-Bruzda E, Kotlinska JH. The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:242–9.CrossRef
113.
Knapp DJ, Overstreet DH, Breese GR. Baclofen blocks expression and sensitization of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal. Alcohol Clin Exp Res. 2007;31(4):582–95.PubMedPubMedCentral
114.
Schwartz TL, Siddiqui UA, Raza S, Costello A. Acamprosate calcium as augmentation therapy for anxiety disorders. Ann Pharmacother. 2010;44(12):1930–2.PubMedCrossRef
115.
Finelli PF, Pueschel SM, Padre-Mendoza T, O'Brien MM. Neurological findings in patients with the fragile-X syndrome. J Neurol Neurosurg Psychiatry. 1985;48(2):150–3.PubMedPubMedCentralCrossRef
116.
Sullivan K, Hatton D, Hammer J, Sideris J, Hooper S, Ornstein P, Bailey Jr D. ADHD symptoms in children with FXS. Am J Med Genet A. 2006;140(21):2275–88.PubMedCrossRef
117.
Kramvis I, Mansvelder HD, Loos M, Meredith R. Hyperactivity, perseveration and increased responding during attentional rule acquisition in the Fragile X mouse model. Front Behav Neurosci. 2013;7:172.PubMedPubMedCentralCrossRef
118.
Dorostkar MM, Zou C, Blazquez-Llorca L, Herms J. Analyzing dendritic spine pathology in Alzheimer's disease: problems and opportunities. Acta Neuropathol. 2015;130(1):1–19.PubMedPubMedCentralCrossRef
119.
Watase K, Zoghbi HY. Modelling brain diseases in mice: the challenges of design and analysis. Nat Rev Genet. 2003;4(4):296–307.PubMedCrossRef
120.
Saivin S, Hulot T, Chabac S, Potgieter A, Durbin P, Houin G. Clinical pharmacokinetics of acamprosate. Clin Pharmacokinet. 1998;35(5):331–45.PubMedCrossRef
121.
Burattini C, McGeehan AJ, Griffin 3rd WC, Gass JT, Kinder JR, Janak PH, Olive MF. A microdialysis study of extracellular levels of acamprosate and naltrexone in the rat brain following acute and repeated administration. Addict Biol. 2008;13(1):70–9.PubMedCrossRef
Metadata
Title
Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety
Authors
Tori L. Schaefer
Matthew H. Davenport
Lindsay M. Grainger
Chandler K. Robinson
Anthony T. Earnheart
Melinda S. Stegman
Anna L. Lang
Amy A. Ashworth
Gemma Molinaro
Kimberly M. Huber
Craig A. Erickson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2017
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/s11689-017-9184-y

Other articles of this Issue 1/2017

Journal of Neurodevelopmental Disorders 1/2017 Go to the issue

Research

Arbaclofen in fragile X syndrome: results of phase 3 trials

Review

Fragile X targeted pharmacotherapy: lessons learned and future directions

Review

Social brain circuitry and social cognition in infants born preterm

Research

Executive functioning in Cornelia de Lange syndrome: domain asynchrony and age-related performance

Research

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome

Research

EEG power at 3 months in infants at high familial risk for autism