Mapping pathological phenotypes in reelin mutant mice

Frontiers in Pediatrics

Volumn 2, Issue SEP, 2014, Pages

  Michetti, Caterina ^a,b   Romano, Emilia ^a,c   Altabella, Luisa ^a   Caruso, Angela ^a,b   Castelluccio, Paolo ^a   Bedse, Gaurav ^b   Gaetani, Silvana ^b   Canese, Rossella ^a   Laviola, Giovanni ^a   Scattoni, Maria Luisa ^a  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

Autism spectrum disorders; Circadian cycle; Dopamine; Glutamate; Reeler mice; Social interaction; Stress response; Ultrasonic vocalizations

Indexed keywords

EID: 84992437960     PISSN: None     EISSN: 22962360     Source Type: Journal    
DOI: 10.3389/fped.2014.00095     Document Type: Article

References (117)

1. American Psychiatric Association, Washington D. Diagnostic and Statistical Manual of Mental Disorders DSM-5. Washington, DC: American Psychiatric Publishing (2013)
2. Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci U S A (1998) 95:15718-23. doi:10.1073/pnas.95.26.15718
3. Guidotti A, Auta J, Davis JM, Di-Giorgi-Gerevini V, Dwivedi Y, Grayson DR, et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry (2000) 57:1061-9. doi:10.1001/archpsyc.57.11.1061
4. Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, et al. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet (2000) 26:93-6. doi:10.1038/79246
5. Fatemi SH. Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly. Mol Psychiatry (2001) 6:129-33. doi:10.1038/sj.mp.4000129
6. Keller F, Persico AM. The neurobiological context of autism. Mol Neurobiol (2003) 28:1-22. doi:10.1385/MN:28:1:1
7. Laviola G, Ognibene E, Romano E, Adriani W, Keller F. Gene-environment interaction during early development in the heterozygous reeler mouse: clues for modelling of major neurobehavioral syndromes. Neurosci Biobehav Rev (2009) 33:560-72. doi:10.1016/j.neubiorev.2008.09.006
8. Folsom TD, Fatemi SH. The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology (2013) 68:122-35. doi:10.1016/j.neuropharm.2012.08.015
9. Keller F, Persico AM, Zelante L, Gasperial P, D'agruma N, Maiorano N, et al. Reelin gene alleles and haplotypes are associated with autistic disorder. Society for Neuroscience. New Orleans (2000) 26:77 (31.11)
10. Fatemi SH, Stary JM, Halt AR, Realmuto GR. Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J Autism Dev Disord (2001) 31:529-35. doi:10.1023/A:1013234708757
11. Fatemi SH, Stary JM, Egan EA. Reduced blood levels of reelin as a vulnerability factor in pathophysiology of autistic disorder. Cell Mol Neurobiol (2002) 22:139-52. doi:10.1023/A:1019857620251
12. Fatemi SH, Snow AV, Stary JM, Araghi-Niknam M, Reutiman TJ, Lee S, et al. Reelin signaling is impaired in autism. Biol Psychiatry (2005) 57:777-87. doi:10.1016/j.biopsych.2004.12.018
13. Krebs MO, Betancur C, Leroy S, Bourdel MC, Gillberg C, Leboyer M. Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism. Mol Psychiatry (2002) 7:801-4. doi:10.1038/sj.mp.4001071
14. Zhang H, Liu X, Zhang C, Mundo E, Macciardi F, Grayson DR, et al. Reelin gene alleles and susceptibility to autism spectrum disorders. Mol Psychiatry (2002) 7:1012-7. doi:10.1038/sj.mp.4001124
15. Bonora E, Beyer KS, Lamb JA, Parr JR, Klauck SM, Benner A, et al. Analysis of reelin as a candidate gene for autism. Mol Psychiatry (2003) 8:885-92. doi:10.1038/sj.mp.4001310
16. Serajee FJ, Zhong H, Mahbubul Huq AH. Association of Reelin gene polymorphisms with autism. Genomics (2006) 87:75-83. doi:10.1016/j.ygeno.2005.09.008
17. Dutta S, Guhathakurta S, Sinha S, Chatterjee A, Ahmed S, Ghosh S, et al. Reelin gene polymorphisms in the Indian population: a possible paternal 5'UTR-CGG-repeat-allele effect on autism. Am J Med Genet B Neuropsychiatr Genet (2007) 144B:106-12. doi:10.1002/ajmg.b.30419
18. Dutta S, Sinha S, Ghosh S, Chatterjee A, Ahmed S, Usha R. Genetic analysis of reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population. Neurosci Lett (2008) 441:56-60. doi:10.1016/j.neulet.2008.06.022
19. He Y, Xun G, Xia K, Hu Z, Lv L, Deng Z, et al. No significant association between RELN polymorphism and autism in case-control and family-based association study in Chinese Han population. Psychiatry Res (2011) 187:462-4. doi:10.1016/j.psychres.2010.04.051
20. Persico AM, D'agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry (2001) 6:150-9. doi:10.1038/sj.mp.4000850
21. Skaar DA, Shao Y, Haines JL, Stenger JE, Jaworski J, Martin ER, et al. Analysis of the RELN gene as a genetic risk factor for autism. Mol Psychiatry (2005) 10:563-71. doi:10.1038/sj.mp.4001614
22. Ashley-Koch AE, Jaworski J, Ma De Q, Mei H, Ritchie MD, Skaar DA, et al. Investigation of potential gene-gene interactions between APOE and RELN contributing to autism risk. Psychiatr Genet (2007) 17:221-6. doi:10.1097/YPG.0b013e32809c2f75
23. Li H, Li Y, Shao J, Li R, Qin Y, Xie C, et al. The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population. Am J Med Genet B Neuropsychiatr Genet (2008) 147B:194-200. doi:10.1002/ajmg.b.30584
24. Holt R, Barnby G, Maestrini E, Bacchelli E, Brocklebank D, Sousa I, et al. Linkage and candidate gene studies of autism spectrum disorders in European populations. Eur J Hum Genet (2010) 18:1013-9. doi:10.1038/ejhg.2010.69
25. Fu X, Mei Z, Sun L. Association between the g.296596G > A genetic variant of RELN gene and susceptibility to autism in a Chinese Han population. Genet Mol Biol (2013) 36:486-9. doi:10.1590/S1415-47572013005000037
26. Sharma JR, ArieffZ, Gameeldien H, Davids M, Kaur M, Van Der Merwe L. Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population. Genet Test Mol Biomarkers (2013) 17:93-8. doi:10.1089/gtmb.2012.0212
27. Wang Z, Hong Y, Zou L, Zhong R, Zhu B, Shen N, et al. Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis. Am J Med Genet B Neuropsychiatr Genet (2014) 165B:192-200. doi:10.1002/ajmg.b.32222
28. Hamburgh M. Analysis of the postnatal developmental effects of "reeler," a neurological mutation in mice. A study in developmental genetics. Dev Biol (1963) 8:165-85. doi:10.1016/0012-1606(63)90040-X
29. Tissir F, Goffinet AM. Reelin and brain development. Nat Rev Neurosci (2003) 4:496-505. doi:10.1038/nrn1113
30. Boyle MP, Bernard A, Thompson CL, Ng L, Boe A, Mortrud M, et al. Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala. J Comp Neurol (2011) 519:2061-89. doi:10.1002/cne.22655
31. Mariani J, Crepel F, Mikoshiba K, Changeux JP, Sotelo C. Anatomical, physiological and biochemical studies of the cerebellum from Reeler mutant mouse. Philos Trans R Soc Lond B Biol Sci (1977) 281:1-28. doi:10.1098/rstb.1977.0121
32. Bailey AJ. The biology of autism. Psychol Med (1993) 23:7-11. doi:10.1017/S0033291700038794
33. Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolumnar pathology in autism. Neurology (2002) 58:428-32. doi:10.1212/WNL.58.3.428
34. Courchesne E, Carper R, AkshoomoffN. Evidence of brain overgrowth in the first year of life in autism. JAMA (2003) 290:337-44. doi:10.1001/jama.290.3.337
35. Palmen SJ, Van Engeland H, Hof PR, Schmitz C. Neuropathological findings in autism. Brain (2004) 127:2572-83. doi:10.1093/brain/awh287
36. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci (2005) 23:183-7. doi:10.1016/j.ijdevneu.2004.09.006
37. Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, et al. The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol (2010) 119:755-70. doi:10.1007/s00401-010-0655-4
38. Schumann CM, Nordahl CW. Bridging the gap between MRI and postmortem research in autism. Brain Res (2011) 1380:175-86. doi:10.1016/j.brainres.2010.09.061
39. Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum (2012) 11:777-807. doi:10.1007/s12311-012-0355-9
40. Biamonte F, Assenza G, Marino R, D'amelio M, Panteri R, Caruso D, et al. Interactions between neuroactive steroids and reelin haploinsufficiency in Purkinje cell survival. Neurobiol Dis (2009) 36:103-15. doi:10.1016/j.nbd.2009.07.001
41. Maloku E, Covelo IR, Hanbauer I, Guidotti A, Kadriu B, Hu Q, et al. Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression. Proc Natl Acad Sci U S A (2010) 107:4407-11. doi:10.1073/pnas.0914483107
42. Pappas GD, Kriho V, Pesold C. Reelin in the extracellular matrix and dendritic spines of the cortex and hippocampus: a comparison between wild type and heterozygous reeler mice by immunoelectron microscopy. J Neurocytol (2001) 30:413-25. doi:10.1023/A:1015017710332
43. Tueting P, Costa E, Dwivedi Y, Guidotti A, Impagnatiello F, Manev R, et al. The phenotypic characteristics of heterozygous reeler mouse. Neuroreport (1999) 10:1329-34. doi:10.1097/00001756-199904260-00032
44. Ognibene E, Adriani W, Granstrem O, Pieretti S, Laviola G. Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice. Brain Res (2007) 1131:173-80. doi:10.1016/j.brainres.2006.11.007
45. Krueger DD, Howell JL, Hebert BF, Olausson P, Taylor JR, Nairn AC. Assessment of cognitive function in the heterozygous reeler mouse. Psychopharmacology (Berl) (2006) 189:95-104. doi:10.1007/s00213-006-0530-0
46. Brigman JL, Padukiewicz KE, Sutherland ML, Rothblat LA. Executive functions in the heterozygous reeler mouse model of schizophrenia. Behav Neurosci (2006) 120:984-8. doi:10.1037/0735-7044.120.4.984
47. Marrone MC, Marinelli S, Biamonte F, Keller F, Sgobio CA, Ammassari-Teule M, et al. Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice. Eur J Neurosci (2006) 24:2061-70. doi:10.1111/j.1460-9568.2006.05083.x
48. Qiu S, Korwek KM, Pratt-Davis AR, Peters M, Bergman MY, Weeber EJ. Cognitive disruption and altered hippocampus synaptic function in Reelin haploinsufficient mice. Neurobiol Learn Mem (2006) 85:228-42. doi:10.1016/j.nlm.2005.11.001
49. Larson J, Hoffman JS, Guidotti A, Costa E. Olfactory discrimination learning deficit in heterozygous reeler mice. Brain Res (2003) 971:40-6. doi:10.1016/S0006-8993(03)02353-9
50. Ammassari-Teule M, Sgobio C, Biamonte F, Marrone C, Mercuri NB, Keller F. Reelin haploinsufficiency reduces the density of PV+ neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors. Psychopharmacology (Berl) (2009) 204:511-21. doi:10.1007/s00213-009-1483-x
51. Macri S, Biamonte F, Romano E, Marino R, Keller F, Laviola G. Perseverative responding and neuroanatomical alterations in adult heterozygous reeler mice are mitigated by neonatal estrogen administration. Psychoneuroendocrinology (2010) 35:1374-87. doi:10.1016/j.psyneuen.2010.03.012
52. Podhorna J, Didriksen M. The heterozygous reeler mouse: behavioural phenotype. Behav Brain Res (2004) 153:43-54. doi:10.1016/j.bbr.2003.10.033
53. Scattoni ML, Ricceri L, Crawley JN. Unusual repertoire of vocalizations in adult BTBR T+tf/J mice during three types of social encounters. Genes Brain Behav (2011) 10:44-56. doi:10.1111/j.1601-183X.2010.00623.x
54. Liu X, Hubbard JA, Fabes RA, Adam JB. Sleep disturbances and correlates of children with autism spectrum disorders. Child Psychiatry Hum Dev (2006) 37:179-91. doi:10.1007/s10578-006-0028-3
55. Malow BA, Marzec ML, Mcgrew SG, Wang L, Henderson LM, Stone WL. Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep (2006) 29:1563-71
56. Goldman SE, Surdyka K, Cuevas R, Adkins K, Wang L, Malow BA. Defining the sleep phenotype in children with autism. Dev Neuropsychol (2009) 34:560-73. doi:10.1080/87565640903133509
57. May T, Cornish K, Conduit R, Rajaratnam SM, Rinehart NJ. Sleep in high-functioning children with autism: longitudinal developmental change and associations with behavior problems. Behav Sleep Med (2013). doi:10.1080/15402002.2013.829064
58. Rugh R. The Mouse: Its Reproduction and Development. New York: Oxford University Press (1990)
59. Scattoni ML, Gandhy SU, Ricceri L, Crawley JN. Unusual repertoire of vocalizations in the BTBR T+tf/J mouse model of autism. PLoS One (2008) 3:e3067. doi:10.1371/journal.pone.0003067
60. Romano E, Michetti C, Caruso A, Laviola G, Scattoni ML. Characterization of neonatal vocal and motor repertoire of reelin mutant mice. PLoS One (2013) 8:e64407. doi:10.1371/journal.pone.0064407
61. Dell'Omo G, Vannoni E, Vyssotski AL, Di Bari MA, Nonno R, Agrimi U, et al. Early behavioural changes in mice infected with BSE and scrapie: automated home cage monitoring reveals prion strain differences. Eur J Neurosci (2002) 16:735-42. doi:10.1046/j.1460-9568.2002.02128.x
62. Adriani W, Caprioli A, Granstrem O, Carli M, Laviola G. The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations. Neurosci Biobehav Rev (2003) 27:639-51. doi:10.1016/j.neubiorev.2003.08.007
63. Romano E, Fuso A, Laviola G. Nicotine restores Wt-like levels of reelin and GAD67 gene expression in brain of heterozygous reeler mice. Neurotox Res (2013) 24:205-15. doi:10.1007/s12640-013-9378-3
64. Cassano T, Gaetani S, Morgese MG, Macheda T, Laconca L, Dipasquale P, et al. Monoaminergic changes in locus coeruleus and dorsal raphe nucleus following noradrenaline depletion. Neurochem Res (2009) 34:1417-26. doi:10.1007/s11064-009-9928-5
65. Paxinos G, Franklin K. The Mouse Brain in Stereotaxic Coordinates. San Diego: Elsevier Academic Press (2001)
66. Canese R, Pisanu ME, Mezzanzanica D, Ricci A, Paris L, Bagnoli M, et al. Characterisation of in vivo ovarian cancer models by quantitative 1H magnetic resonance spectroscopy and diffusion-weighted imaging. NMR Biomed (2012) 25:632-42. doi:10.1002/nbm.1779
67. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med (1993) 30:672-9. doi:10.1002/mrm.1910300604
68. Johnson KP, Giannotti F, Cortesi F. Sleep patterns in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am (2009) 18:917-28. doi:10.1016/j.chc.2009.04.001
69. Glickman G. Circadian rhythms and sleep in children with autism. Neurosci Biobehav Rev (2010) 34:755-68. doi:10.1016/j.neubiorev.2009.11.017
70. Rzepecka H, Mckenzie K, Mcclure I, Murphy S. Sleep, anxiety and challenging behaviour in children with intellectual disability and/or autism spectrum disorder. Res Dev Disabil (2011) 32:2758-66. doi:10.1016/j.ridd.2011.05.034
71. Kotagal S, Broomall E. Sleep in children with autism spectrum disorder. Pediatr Neurol (2012) 47:242-51. doi:10.1016/j.pediatrneurol.2012.05.007
72. Fonken LK, Finy MS, Walton JC, Weil ZM, Workman JL, Ross J, et al. Influence of light at night on murine anxiety-and depressive-like responses. Behav Brain Res (2009) 205:349-54. doi:10.1016/j.bbr.2009.07.001
73. Menet JS, Rosbash M. When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders. Curr Opin Neurobiol (2011) 21:849-57. doi:10.1016/j.conb.2011.06.008
74. Griesauer I, Diao W, Ronovsky M, Elbau I, Sartori S, Singewald N, et al. Circadian abnormalities in a mouse model of high trait anxiety and depression. Ann Med (2014) 46:148-54. doi:10.3109/07853890.2013.866440
75. Badea A, Nicholls PJ, Johnson GA, Wetsel WC. Neuroanatomical phenotypes in the reeler mouse. Neuroimage (2007) 34:1363-74. doi:10.1016/j.neuroimage.2006.09.053
76. Niu S, Renfro A, Quattrocchi CC, Sheldon M, D'Arcangelo G. Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway. Neuron (2004) 41:71-84. doi:10.1016/S0896-6273(03)00819-5
77. Stranahan AM, Erion JR, Wosiski-Kuhn M. Reelin signaling in development, maintenance, and plasticity of neural networks. Ageing Res Rev (2013) 12:815-22. doi:10.1016/j.arr.2013.01.005
78. Costa E, Davis J, Grayson DR, Guidotti A, Pappas GD, Pesold C. Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability. Neurobiol Dis (2001) 8:723-42. doi:10.1006/nbdi.2001.0436
79. Falconer DS. Two new mutants, 'trembler' and 'reeler', with neurological actions in the house mouse (Mus musculus L.). J Genet (1951) 50:192-201. doi:10.1007/BF02996215
80. Caviness VS Jr, Sidman RL. Time of origin or corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: an autoradiographic analysis. J Comp Neurol (1973) 148:141-51. doi:10.1002/cne.901480202
81. Goffinet AM. An early development defect in the cerebral cortex of the reeler mouse. A morphological study leading to a hypothesis concerning the action of the mutant gene. Anat Embryol (Berl) (1979) 157:205-16. doi:10.1007/BF00305160
82. D'Arcangelo G, Curran T. Reeler: new tales on an old mutant mouse. Bioessays (1998) 20:235-44. doi:10.1002/(SICI)1521-1878(199803)20:3<235::AID-BIES7>3.0.CO;2-Q
83. Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci U S A (2008) 105:1710-5. doi:10.1073/pnas.0711555105
84. Radyushkin K, Hammerschmidt K, Boretius S, Varoqueaux F, El-Kordi A, Ronnenberg A, et al. Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav (2009) 8:416-25. doi:10.1111/j.1601-183X.2009.00487.x
85. Brielmaier J, Matteson PG, Silverman JL, Senerth JM, Kelly S, Genestine M, et al. Autism-relevant social abnormalities and cognitive deficits in engrailed-2 knockout mice. PLoS One (2012) 7:e40914. doi:10.1371/journal.pone.0040914
86. Gandal MJ, Anderson RL, Billingslea EN, Carlson GC, Roberts TP, Siegel SJ. Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia? Genes Brain Behav (2012) 11:740-50. doi:10.1111/j.1601-183X.2012.00816.x
87. Rotschafer SE, Trujillo MS, Dansie LE, Ethell IM, Razak KA. Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X Syndrome. Brain Res (2012) 1439:7-14. doi:10.1016/j.brainres.2011.12.041
88. Yang M, Bozdagi O, Scattoni ML, Wohr M, Roullet FI, Katz AM, et al. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J Neurosci (2012) 32:6525-41. doi:10.1523/JNEUROSCI.6107-11.2012
89. Salinger WL, Ladrow P, Wheeler C. Behavioral phenotype of the reeler mutant mouse: effects of RELN gene dosage and social isolation. Behav Neurosci (2003) 117:1257-75. doi:10.1037/0735-7044.117.6.1257
90. Laviola G, Adriani W, Gaudino C, Marino R, Keller F. Paradoxical effects of prenatal acetylcholinesterase blockade on neuro-behavioral development and drug-induced stereotypies in reeler mutant mice. Psychopharmacology (Berl) (2006) 187:331-44. doi:10.1007/s00213-006-0426-z
91. Ognibene E, Adriani W, Macri S, Laviola G. Neurobehavioural disorders in the infant reeler mouse model: interaction of genetic vulnerability and consequences of maternal separation. Behav Brain Res (2007) 177:142-9. doi:10.1016/j.bbr.2006.10.027
92. Ognibene E, Adriani W, Caprioli A, Ghirardi O, Ali SF, Aloe L, et al. The effect of early maternal separation on brain derived neurotrophic factor and monoamine levels in adult heterozygous reeler mice. Prog Neuropsychopharmacol Biol Psychiatry (2008) 32:1269-76. doi:10.1016/j.pnpbp.2008.03.023
93. Ballmaier M, Zoli M, Leo G, Agnati LF, Spano P. Preferential alterations in the mesolimbic dopamine pathway of heterozygous reeler mice: an emerging animal-based model of schizophrenia. Eur J Neurosci (2002) 15:1197-205. doi:10.1046/j.1460-9568.2002.01952.x
94. Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci (2002) 3:715-27. doi:10.1038/nrn919
95. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol (2002) 213:1-47. doi:10.1016/S0074-7696(02)13011-7
96. Wang L, Bruce G, Spary E, Deuchars J, Deuchars SA. GABA(B) mediated regulation of sympathetic preganglionic neurons: pre-and postsynaptic sites of action. Front Neurol (2010) 1:142. doi:10.3389/fneur.2010.00142
97. Dawson G, Webb SJ, Mcpartland J. Understanding the nature of face processing impairment in autism: insights from behavioral and electrophysiological studies. Dev Neuropsychol (2005) 27:403-24. doi:10.1207/s15326942dn2703_6
98. Schultz RT. Developmental deficits in social perception in autism: the role of the amygdala and fusiform face area. Int J Dev Neurosci (2005) 23:125-41. doi:10.1016/j.ijdevneu.2004.12.012
99. Pezze MA, Feldon J. Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol (2004) 74:301-20. doi:10.1016/j.pneurobio.2004.09.004
100. Rinaldi A, Mandillo S, Oliverio A, Mele A. D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice. Neuropsychopharmacology (2007) 32:309-19. doi:10.1038/sj.npp.1301176
101. Tran T, Ross B, Lin A. Magnetic resonance spectroscopy in neurological diagnosis. Neurol Clin (2009) 27:21-60,xiii. doi:10.1016/j.ncl.2008.09.007
102. Chugani DC. Neuroimaging and neurochemistry of autism. Pediatr Clin North Am (2012) 59:63-73,x. doi:10.1016/j.pcl.2011.10.002
103. Olney JW, de GubareffT. Glutamate neurotoxicity and Huntington's chorea. Nature (1978) 271:557-9. doi:10.1038/271557a0
104. Tsai VW, Scott HL, Lewis RJ, Dodd PR. The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in Alzheimer's disease. Neurotox Res (2005) 7:125-41. doi:10.1007/BF03033782
105. Estrada-Sanchez AM, Montiel T, Segovia J, Massieu L. Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol Dis (2009) 34:78-86. doi:10.1016/j.nbd.2008.12.017
106. Page LA, Daly E, Schmitz N, Simmons A, Toal F, Deeley Q, et al. In vivo 1H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism. Am J Psychiatry (2006) 163:2189-92. doi:10.1176/appi.ajp.163.12.2189
107. Bejjani A, O'neill J, Kim JA, Frew AJ, Yee VW, Ly R, et al. Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI. PLoS One (2012) 7:e38786. doi:10.1371/journal.pone.0038786
108. Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, et al. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med (2012) 4:131ra151. doi:10.1126/scitranslmed.3003501
109. Wu JY, Wu H, Jin Y, Wei J, Sha D, Prentice H, et al. Mechanism of neuroprotective function of taurine. Adv Exp Med Biol (2009) 643:169-79. doi:10.1007/978-0-387-75681-3_17
110. Ipser JC, Syal S, Bentley J, Adnams CM, Steyn B, Stein DJ. 1H-MRS in autism spectrum disorders: a systematic meta-analysis. Metab Brain Dis (2012) 27:275-87. doi:10.1007/s11011-012-9293-y
111. Canese R, Pisanu ME, Mezzanzanica D, Ricci A, Paris L, Bagnoli M, et al. Characterisation of in vivo ovarian cancer models by quantitative 1H magnetic resonance spectroscopy and diffusion-weighted imaging. NMR Biomed (2011) 25:632-42. doi:10.1002/nbm.1779
112. Adriani W, Canese R, Podo F, Laviola G. 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence. Neurotoxicol Teratol (2007) 29:116-25. doi:10.1016/j.ntt.2006.11.010
113. Marco EM, Adriani W, Canese R, Podo F, Viveros MP, Laviola G. Enhancement of endocannabinoid signalling during adolescence: modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats. Pharmacol Biochem Behav (2007) 86:334-45. doi:10.1016/j.pbb.2006.10.006
114. De Filippis B, Fabbri A, Simone D, Canese R, Ricceri L, Malchiodi-Albedi F, et al. Modulation of RhoGTPases improves the behavioral phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome. Neuropsychopharmacology (2011) 37:1152-63. doi:10.1038/npp.2011.301
115. Fatemi SH, Stary JM, Earle JA, Araghi-Niknam M, Eagan E. GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum. Schizophr Res (2005) 72:109-22. doi:10.1016/j.schres.2004.02.017
116. Eastwood SL, Harrison PJ. Cellular basis of reduced cortical reelin expression in schizophrenia. Am J Psychiatry (2006) 163:540-2. doi:10.1176/appi.ajp.163.3.540
117. Tremolizzo L, Carboni G, Ruzicka WB, Mitchell CP, Sugaya I, Tueting P, et al. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc Natl Acad Sci U S A (2002) 99:17095-100. doi:10.1073/pnas.262658999