Timing of therapies for downsyndrome: The sooner, the better

Frontiers in Behavioral Neuroscience

Volumn 9, Issue OCT, 2015, Pages

  Stagni, Fiorenza ^a   Giacomini, Andrea ^a   Guidi, Sandra ^a   Ciani, Elisabetta ^a   Bartesaghi, Renata ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Adult therapies; Down syndrome; Intellectual disability; Mouse models; Perinatal therapies

Indexed keywords

2 METHYL 6 (5 METHYL 3 PHENYL 4 ISOXAZOLYLMETHOXY)PYRIDINE; 3 BROMO 10 DIFLUOROMETHYL 9H BENZO[F]IMIDAZO[1,5 A][1,2,4]TRIAZOLO[1,5 D][1,4]DIAZEPINE; 4 BENZYL ALPHA (4 HYDROXYPHENYL) BETA METHYL 1 PIPERIDINEPROPANOL; 4 [BIS(1,3 BENZODIOXOL 5 YL)HYDROXYMETHYL] 1 PIPERIDINECARBOXYLIC ACID 4 NITROPHENYL ESTER; ALPHA TOCOPHEROL; BENZYL[3 [[1 (3,4 DICHLOROPHENYL)ETHYL]AMINO] 2 HYDROXYPROPYL]PHOSPHINIC ACID; CHOLINE; CLOZAPINE N OXIDE; DONEPEZIL; EPIGALLOCATECHIN GALLATE; ESTROGEN; ETHOSUXIMIDE; FLUOXETINE; FORMOTEROL; GABAPENTIN; GALANTAMINE; MELATONIN; MEMANTINE; MINOCYCLINE; PENTETRAZOLE; PHYSOSTIGMINE; PICROTOXIN; PIRACETAM; RIVASTIGMINE; XAMOTEROL;

BRAIN DEVELOPMENT; CEREBELLUM; DOWN SYNDROME; FETAL THERAPY; GABAERGIC SYSTEM; HIPPOCAMPUS; HUMAN; INTELLECTUAL IMPAIRMENT; LONG TERM POTENTIATION; MOUSE MODEL; NERVE DEGENERATION; NONHUMAN; NORADRENERGIC SYSTEM; PRENATAL DRUG EXPOSURE; REVIEW; SEROTONINERGIC SYSTEM; TIME TO TREATMENT; TRISOMY;

EID: 84944458456     PISSN: 16625153     EISSN: None     Source Type: Journal    
DOI: 10.3389/fnbeh.2015.00265     Document Type: Review

References (114)

1. Abbas, A. K., Villers, A., and Ris, L. (2015). Temporal phases of longterm potentiation (LTP): myth or fact? Rev. Neurosci. 26, 507-546. doi: 10.1515/revneuro-2014-0072
2. Abraham, H., Tornóczky, T., Kosztolanyi, G., and Seress, L. (2001). Cell formation in the cortical layers of the developing human cerebellum. Int. J. Dev. Neurosci. 19, 53-62. doi: 10.1016/S0736-5748(00) 00065-4
3. Ahmed, M. M., Dhanasekaran, A. R., Block, A., Tong, S., Costa, A. C., Stasko, M. et al. (2015). Protein dynamics associated with failed and rescued learning in the Ts65Dn mouse model of Down syndrome. PLoS ONE 10:e0119491. doi: 10.1371/journal.pone.0119491
4. Alcami Pertejo, M., Peral Guerra, M., and Gilaberte, I. (2000). Open study of fluoxetine in children with autism. Actas Esp. Psiquiatr. 28, 353-356.
5. Altman, J., and Bayer, S. (1975). “Postnatal development of the hippocampal dentate gyrus under normal and experimental conditions,” in The Hippocampus, Vol. 1, eds R. L. Isaacson and K. H. Pribram (New York, NY; London: Plenum Press), 95-122.
6. Altman, J., and Bayer, S. A. (1990a). Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells. J. Comp. Neurol. 301, 325-342. doi: 10.1002/cne.903010302
7. Altman, J., and Bayer, S. A. (1990b). Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J. Comp. Neurol. 301, 365-381. doi: 10.1002/cne.903010304
8. Ash, J. A., Velazquez, R., Kelley, C. M., Powers, B. E., Ginsberg, S. D., Mufson, E. J., et al. (2014). Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice. Neurobiol. Dis. 70, 32-42. doi: 10.1016/j.nbd.2014.06.001
9. Baggot, P. J., and Baggot, R. M. (2014). Fetal therapy for Down syndrome: report of three cases and a review of the literature. J. Am. Phys. Surg. 19, 20-24.
10. Bartesaghi, R., Guidi, S., and Ciani, E. (2011). Is it possible to improve neurodevelopmental abnormalities in Down syndrome? Rev. Neurosci. 22, 419-455. doi: 10.1515/rns.2011.037
11. Becker, L., Mito, T., Takashima, S., and Onodera, K. (1991). Growth and development of the brain in Down syndrome. Prog. Clin. Biol. Res. 373, 133-152.
12. Begenisic, T., Baroncelli, L., Sansevero, G., Milanese, M., Bonifacino, T., Bonanno, G., et al. (2014). Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of Down syndrome. Neurobiol. Dis. 63, 12-19. doi: 10.1016/j.nbd.2013.11.010
13. Belichenko, P. V., Masliah, E., Kleschevnikov, A. M., Villar, A. J., Epstein, C. J., Salehi, A., et al. (2004). Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome. J. Comp. Neurol. 480, 281-298. doi: 10.1002/cne.20337
14. Benavides-Piccione, R., Ballesteros-Yáñez, I., de Lagrán, M. M., Elston, G., Estivill, X., Fillat, C., et al. (2004). On dendrites in Down syndrome and DS murine models: a spiny way to learn. Prog Neurobiol. 74, 111-126. doi: 10.1016/j.pneurobio.2004.08.001
15. Bianchi, P., Ciani, E., Contestabile, A., Guidi, S., and Bartesaghi, R. (2010a). Lithium restores neurogenesis in the subventricular zone of the Ts65Dn mouse, a model for down syndrome. Brain Pathol. 20, 106-118. doi: 10.1111/j.1750-3639.2008.00246.x
16. Bianchi, P., Ciani, E., Guidi, S., Trazzi, S., Felice, D., Grossi, G., et al. (2010b). Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for Down syndrome. J. Neurosci. 30, 8769-8779. doi: 10.1523/JNEUROSCI.0534-10.2010
17. Blanchard, J., Bolognin, S., Chohan, M. O., Rabe, A., Iqbal, K., and Grundke-Iqbal, I.(2011). Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome. J. Neuropathol. Exp. Neurol. 70, 1070-1079. doi: 10.1097/NEN.0b013e318236e9ad
18. Chakrabarti, L., Best, T. K., Cramer, N. P., Carney, R. S., Isaac, J. T., Galdzicki, Z., et al. (2010). Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat. Neurosci. 13, 927-934. doi: 10.1038/nn.2600
19. Chakrabarti, L., Galdzicki, Z., and Haydar, T. F. (2007). Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. J. Neurosci. 27, 11483-11495. doi: 10.1523/JNEUROSCI.3406-07.2007
20. Chambers, C. D., Hernandez-Diaz, S., Van Marter, L. J., Werler, M. M., Louik, C., Jones, K. L., et al. (2006). Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N. Engl. J. Med. 354, 579-587. doi: 10.1056/NEJMoa052744
21. Chang, Q., and Gold, P. E. (2008). Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome. Neurobiol. Learn. Mem. 89, 167-177. doi: 10.1016/j.nlm.2007.05.007
22. Clark, S., Schwalbe, J., Stasko, M. R., Yarowsky, P. J., and Costa, A. C. (2006). Fluoxetine rescues deficient neurogenesis in hippocampus of the Ts65Dn mouse model for Down syndrome. Exp. Neurol. 200, 256-261. doi: 10.1016/j.expneurol.2006.02.005
23. Colas, D., Chuluun, B., Warrier, D., Blank, M., Wetmore, D. Z., Buckmaster, P., et al. (2013). Short-term treatment with the GABAA receptor antagonist pentylenetetrazole produces a sustained pro-cognitive benefit in a mouse model of Down's syndrome. Br. J. Pharmacol. 169, 963-973. doi: 10.1111/bph.12169
24. Contestabile, A., Fila, T., Ceccarelli, C., Bonasoni, P., Bonapace, L., Santini, D., et al. (2007). Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in Ts65Dn mice. Hippocampus 17, 665-678. doi: 10.1002/hipo.20308
25. Contestabile, A., Greco, B., Ghezzi, D., Tucci, V., Benfenati, F., and Gasparini, L. (2013). Lithium rescues synaptic plasticity and memory in Down syndrome mice. J. Clin. Invest. 123, 348-361. doi: 10.1172/JCI64650
26. Corrales, A., Martínez, P., García, S., Vidal, V., García, E., Flórez, J., et al. (2013). Long-term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle-aged Ts65Dn mice, a model of Down syndrome. J. Pineal Res. 54, 346-358. doi: 10.1111/jpi.12037
27. Corrales, A., Vidal, R., García, S., Vidal, V., Martínez, P., García, E., et al. (2014). Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome. J. Pineal Res. 56, 51-61. doi: 10.1111/jpi.12097
28. Costa, A. C., and Grybko, M. J. (2005). 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. doi: 10.1016/j.neulet.2005.03.031
29. Costa, A. C., and Scott-McKean, J. J. (2013). Prospects for improving brain function in individuals with down syndrome. CNS Drugs 27, 679-702. doi: 10.1007/s40263-013-0089-3
30. Costa, A. C., Scott-McKean, J. J., and Stasko, M. R. (2008). 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. doi: 10.1038/sj.npp.1301535
31. Dang, V., Medina, B., Das, D., Moghadam, S., Martin, K. J., Lin, B., et al. (2014). Formoterol, a long-acting beta2 adrenergic agonist, improves cognitive function and promotes dendritic complexity in a mouse model of Down syndrome. Biol. Psychiatry. 75, 179-188. doi: 10.1016/j.biopsych.2013.05.024
32. Das, I., Park, J. M., Shin, J. H., Jeon, S. K., Lorenzi, H., Linden, D. J., et al. (2013). Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model. Sci. Transl. Med. 5, 201ra120. doi: 10.1126/scitranslmed.3005983
33. Davisson, M. T., Schmidt, C., and Akeson, E. C. (1990). Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog. Clin. Biol. Res. 360, 263-280.
34. De la Torre, R., De Sola, S., Pons, M., Duchon, A., de Lagran, M. M., Farré, M., et al. (2014). Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol. Nutr. Food Res. 58, 278-288. doi: 10.1002/mnfr.201300325
35. DeLong, G. R., Ritch, C. R., and Burch, S. (2002). Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement. Dev. Med. Child Neurol. 44, 652-659. doi: 10.1111/j.1469-8749.2002.tb00266.x
36. de Souza, F. M., Busquet, N., Blatner, M., Maclean, K. N., and Restrepo, D. (2011). Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome. Sci. Rep. 1:137. doi: 10.1038/srep00137
37. Dierssen, M. (2012). Down syndrome: the brain in trisomic mode. Nat. Rev. Neurosci. 13, 844-858. doi: 10.1038/nrn3314
38. Einarson, A., Choi, J., Einarson, T. R., and Koren, G. (2009). Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study. Can. J. Psychiatry. 54, 242-246. doi: 10.1016/j.ntt.2008.03.044
39. Eriksson, P. S., Perfilieva, E., Björk-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A., et al. (1998). Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313-1317. doi: 10.1038/3305
40. Faber, K. M., and Haring, J. H. (1999). Synaptogenesis in the postnatal rat fascia dentata is influenced by 5-HT1a receptor activation. Brain Res. Dev. Brain Res. 114, 245-252. doi: 10.1016/S0165-3806(99)00036-X
41. Faizi, M., Bader, P. L., Tun, C., Encarnacion, A., Kleschevnikov, A., Belichenko, P., et al. (2011). Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down syndrome: activation of beta1-adrenergic receptor by xamoterol as a potential cognitive enhancer. Neurobiol. Dis. 43, 397-413. doi: 10.1016/j.nbd.2011.04.011
42. Fernandez, F., Morishita, W., Zuniga, E., Nguyen, J., Blank, M., Malenka, R. C., et al. (2007). Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat. Neurosci. 10, 411-413. doi: 10.1038/nn1860
43. Fortress, A. M., Hamlett, E. D., Vazey, E. M., Aston-Jones, G., Cass, W. A., Boger, H. A., et al. (2015). Designer receptors enhance memory in a mouse model of Down syndrome. J. Neurosci. 35, 1343-1353. doi: 10.1523/JNEUROSCI.2658-14.2015
44. Furu, K., Kieler, H., Haglund, B., Selmer, R., Stephannson, O., and Nørgaaed, M. (2015). Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ 350:h1798. doi: 10.1136/bmj.h1798
45. Gardiner, K. J. (2015). Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations. Drug Des. Devel. Ther. 9, 103-125. doi: 10.2147/DDDT.S51476
46. Gozes, I., Divinski, I., and Piltzer, I. (2008). NAP and D-SAL: neuroprotection against the beta amyloid peptide (1-42). BMC Neurosci. 9(Suppl. 3):S3. doi: 10.1186/1471-2202-9-S3-S3
47. Gozes, I., Morimoto, B. H., Tiong, J., Fox, A., Sutherland, K., Dangoor, D., et al. (2005). NAP: research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP). CNS Drug Rev. 11, 353-368. doi: 10.1111/j.1527-3458.2005.tb00053.x
48. Granholm, A. C., Ford, K. A., Hyde, L. A., Bimonte, H. A., Hunter, C. L., Nelson, M., et al. (2002). Estrogen restores cognition and cholinergic phenotype in an animal model of Down syndrome. Physiol. Behav. 77, 371-385. doi: 10.1016/S0031-9384(02)00884-3
49. Granholm, A. C., Sanders, L., Seo, H., Lin, L., Ford, K., and Isacson, O. (2003). Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome. Hippocampus 13, 905-914. doi: 10.1002/hipo.10130
50. Guedj, F., and Bianchi, D. W. (2013). Noninvasive prenatal testing creates an opportunity for antenatal treatment of Down syndrome. Prenat. Diagn. 33, 614-618. doi: 10.1002/pd.4134
51. Guedj, F., Bianchi, D. W., and Delabar, J. M. (2014). Prenatal treatment of Down syndrome: a reality? Curr. Opin. Obstet. Gynecol. 26, 92-103. doi: 10.1097/gco.0000000000000056
52. Guedj, F., Sébrié, C., Rivals, I., Ledru, A., Paly, E., Bizot, J. C., et al. (2009). Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS ONE 4:e4606. doi: 10.1371/journal.pone.0004606
53. Guidi, S., Bonasoni, P., Ceccarelli, C., Santini, D., Gualtieri, F., Ciani, E., et al. (2008). Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome. Brain Pathol. 18, 180-197. doi: 10.1111/j.1750-3639.2007.00113.x
54. Guidi, S., Ciani, E., Bonasoni, P., Santini, D., and Bartesaghi, R. (2011). Widespread proliferation impairment and hypocellularity in the cerebellum of fetuses with Down syndrome. Brain Pathol. 21, 361-373. doi: 10.1111/j.1750-3639.2010.00459.x
55. Guidi, S., Stagni, F., Bianchi, P., Ciani, E., Giacomini, A., De Franceschi, M., et al. (2014). Prenatal pharmacotherapy rescues brain development in a Down’s syndrome mouse model. Brain 137, 380-401. doi: 10.1093/brain/awt340
56. Guidi, S., Stagni, F., Bianchi, P., Ciani, E., Ragazzi, E., Trazzi, S., et al. (2013). Early pharmacotherapy with fluoxetine rescues dendritic pathology in the Ts65Dn mouse model of Down syndrome. Brain Pathol. 23, 129-143. doi: 10.1111/j.1750-3639.2012.00624.x
57. Gutierrez-Castellanos, N., Winkelman, B. H., Tolosa-Rodriguez, L., Devenney, B., Reeves, R. H., and De Zeeuw, C. I. (2013). Size does not always matter: Ts65Dn Down syndrome mice show cerebellum-dependent motor learning deficits that cannot be rescued by postnatal SAG treatment. J. Neurosci. 33, 15408-15413. doi: 10.1523/JNEUROSCI.2198-13.2013
58. Hanson, J. E., Weber, M., Meilandt, W. J., Wu, T., Luu, T., Deng, L., et al. (2013). GluN2B antagonism affects interneurons and leads to immediate and persistent changes in synaptic plasticity, oscillations, and behavior. Neuropsychopharmacology 38, 1221-1233. doi: 10.1038/npp.2013.19
59. Hayes, R. M., Wu, P., Shelton, R. C., Cooper, W. O., Dupont, W. D., Mitchel, E., et al. (2012). Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies. Am. J. Obstet. Gynecol. 207, e41-e49. doi: 10.1016/j.ajog.2012.04.028
60. Heinen, M., Hettich, M. M., Ryan, D. P., Schnell, S., Paesler, K., and Ehninger, D.(2012). Adult-onset fluoxetine treatment does not improve behavioral impairments and may have adverse effects on the Ts65Dn mouse model of Down syndrome. NeuralPlast. 2012:467251. doi: 10.1155/2012/467251
61. Hollander, E., Phillips, A., Chaplin, W., Zagursky, K., Novotny, S., Wasserman, S., et al. (2005). A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology 30, 582-589. doi: 10.1038/sj.npp.1300627
62. Hunter, C. L., Bachman, D., and Granholm, A. C. (2004). Minocycline prevents cholinergic loss in a mouse model of Down's syndrome. Ann. Neurol. 56, 675-688. doi: 10.1002/ana.20250
63. Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., et al. (2008). Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat. Neurosci. 11, 1153-1161. doi: 10.1038/nn.2185
64. Incerti, M., Horowitz, K., Roberson, R., Abebe, D., Toso, L., Caballero, M., et al. (2012). Prenatal treatment prevents learning deficit in Down syndrome model. PLoS ONE 7:e50724. doi: 10.1371/journal.pone.0050724
65. Incerti, M., Toso, L., Vink, J., Roberson, R., Nold, C., Abebe, D., et al. (2011). Prevention of learning deficit in a Down syndrome model. Obstet. Gynecol. 117, 354-361. doi: 10.1097/AOG.0b013e3182051ca5
66. Isbrucker, R. A., Edwards, J. A., Wolz, E., Davidovich, A., and Bausch, J. (2006). Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: teratogenicity and reproductive toxicity studies in rats. Food Chem. Toxicol. 55, 651-661. doi: 10.1016/j.fct.2005.11.002
67. Kelley, C. M., Powers, B. E., Velazquez, R., Ash, J. A., Ginsberg, S. D., Strupp, B.J., et al. (2014). Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice. J. Comp. Neurol. 522, 1390-1410. doi: 10.1002/cne.23492
68. Kim, H. S., Quon, M. J., and Kim, J. A. (2014). New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol. 2, 187-195. doi: 10.1016/j.redox.2013.12.022
69. Kleschevnikov, A. M., Belichenko, P. V., Faizi, M., Jacobs, L. F., Htun, K., Shamloo, M., et al. (2012). Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists. J. Neurosci. 32, 9217-9227. doi: 10.1523/JNEUROSCI.1673-12.2012
70. Kleschevnikov, A. M., Belichenko, P. V., Villar, A. J., Epstein, C. J., Malenka, R. C., and Mobley, W. C. (2004). Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J. Neurosci. 24, 8153-8160. doi: 10.1523/JNEUROSCI.1766-04.2004
71. Lambert, J. D., Kennett, M. J., Sang, S., Rehul, K. R., Ju, J., and Yang, C. S. (2009). Hepatotoxicity of High Oral Dose (-)-Epigallocatechin-3-Gallate in Mice. Food Chem. Toxicol. 2010,409-416. doi: 10.1016/j.fct.2009.10.030
72. Latchney, S. E., Jaramillo, T. C., Rivera, P. D., Eisch, A. J., and Powell, C. M. (2015). Chronic P7C3 treatment restores hippocampal neurogenesis. Neurosci. Lett. 591, 86-92. doi: 10.1016/j.neulet.2015.02.008
73. Lockrow, J., Boger, H., Bimonte-Nelson, H., and Granholm, A. C. (2011). Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome. Behav. Brain Res. 221, 610-622. doi: 10.1016/j.bbr.2010.03.036
74. Lockrow, J., Prakasam, A., Huang, P., Bimonte-Nelson, H., Sambamurti, K., and Granholm, A. C. (2009). Cholinergic degeneration and memoryloss delayed by vitamin E in a Down syndrome mouse model. Exp. Neurol. 216, 278-289. doi: 10.1016/j.expneurol.2008.11.021
75. Lysenko, L. V., Kim, J., Henry, C., Tyrtyshnaia, A., Kohnz, R. A., Madamba, F., et al. (2014). Monoacylglycerol lipase inhibitor JZL184 improves behavior and neural properties in Ts65Dn mice, a model of down syndrome. PLoS ONE 9:e114521. doi: 10.1371/journal.pone.0114521
76. Martínez-Cué, C., Martínez, P., Rueda, N., Vidal, R., García, S., Vidal, V., et al. (2013). Reducing GABAA alpha5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome. J. Neurosci. 33, 3953-3966. doi: 10.1523/JNEUROSCI.1203-12.2013
77. Moon, J., Chen, M., Gandhy, S. U., Strawderman, M., Levitsky, D. A., Maclean, K. N., et al. (2010). Perinatal choline supplementation improves cognitive functioning and emotion regulation in the Ts65Dn mouse model of Down syndrome. Behav. Neurosci. 124, 346-361. doi: 10.1037/a0019590
78. Moran, T. H., Capone, G. T., Knipp, S., Davisson, M. T., Reeves, R. H., and Gearhart, J. D. (2002). The effects of piracetam on cognitive performance in a mouse model of Down’s syndrome. Physiol. Behav. 77, 403-409. doi: 10.1016/S0031-9384(02)00873-9
79. Moses-Kolko, E. L., Bogen, D., Perel, J., Bregar, A., Uhl, K., Levin, B., et al. (2005). Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 293, 2372-2383. doi: 10.1001/jama.293.19.2372
80. Netzer, W. J., Powell, C., Nong, Y., Blundell, J., Wong, L., Duff, K., et al. (2010). Lowering beta-amyloid levels rescues learning and memory in a Down syndrome mouse model. PLoS ONE 5:e10943. doi: 10.1371/journal.pone.0010943
81. Olivier, J., Akerud, H., Kaihola, L., Pawluski, J., Skalkidou, S., Hogberg, U., et al. (2013). The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring. Front. Cell Neurosci. 7:73. doi: 10.3389/fncel.2013.00073
82. Pedersen, L. H., Henriksen, T. B., and Olsen, J. (2010). Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age. Pediatrics 125, e600-e608. doi: 10.1542/peds.2008-3655
83. Perrone, S., Longini, M., Bellieni, C. V., Centini, G., Kenanidis, A., De Marco, L., et al. (2007). Early oxidative stress in amniotic fluid of pregnancies with Down syndrome. Clin. Biochem. 40, 177-180. doi: 10.1016/j.clinbiochem.2006.10.019
84. Pons-Espinal, M., Martínez de Lagrán, M., and Dierssen, M. (2013). Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A. Neurobiol. Dis. 60, 18-31. doi: 10.1016/j.nbd.2013.08.008
85. Rachidi, M., and Lopes, C. (2008). Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways. Eur. J. Paediatr. Neurol. 12, 168-182. doi: 10.1016/j.ejpn.2007.08.010
86. Reefhuis, J., Devine, O., Friedman, J. M., Louik, K., and Honein, M. (2015). Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ 350:h3190. doi: 10.1136/bmj.h3190
87. Rice, D., and Barone, S. (2010). Critical periods of vulnerabiliy for the developing nervpus system: evidence from humans and animal models. Environ. Health Perspect. 108(Suppl. 3), 511-533. doi: 10.1289/ehp.00108s3511
88. Roper, R. J., Baxter, L. L., Saran, N. G., Klinedinst, D. K., Beachy, P. A., and Reeves, R. H. (2006). Defective cerebellar response to mitogenic Hedgehog signaling in Down [corrected] syndrome mice. Proc.Natl. Acad. Sci. U.S.A. 103, 1452-1456. doi: 10.1073/pnas.0510750103
89. Rueda, N., Flórez, J., and Martínez-Cué, C. (2008a). Chronic pentylenetetrazole but not donepezil treatment rescues spatial cognition in Ts65Dn mice, a model for Down syndrome. Neurosci. Lett. 433, 22-27. doi: 10.1016/j.neulet.2007.12.039
90. Rueda, N., Flórez, J., and Martínez-Cué, C. (2008b). Effects of chronic administration of SGS-111 during adulthood and during the pre-and postnatal periods on the cognitive deficits of Ts65Dn mice, a model of Down syndrome. Behav. Brain Res. 188, 355-367. doi: 10.1016/j.bbr.2007.11.020
91. Rueda, N., Flórez, J., and Martínez-Cué, C. (2012). Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities. Neural Plast. 2012, 1-26. doi: 10.1155/2012/584071
92. Rueda, N., Llorens-Martin, M., Flórez, J., Valdizan, E., Banerjee, P., Trejo, J. L., et al. (2010). Memantine normalizes several phenotypic features in the Ts65Dn mouse model of Down syndrome. J. Alzheimers Dis. 21, 277-290. doi: 10.3233/JAD-2010-100240
93. Salehi, A., Faizi, M., Colas, D., Valletta, J., Laguna, J., Takimoto-Kimura, R., et al. (2009). Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. Sci. Transl. Med. 1, 7ra17. doi: 10.1126/scitranslmed.3000258
94. Sanz, E. J., De-las-Cuevas, C., Kiuru, A., Bate, A., and Edwards, R. (2005). Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 365, 482-487. doi: 10.1016/S0140-6736(05)70271-3
95. Seress, L., Abraham, H., Tornóczky, T., and Kosztolanyi, G. (2001). Cell formation in the human hippocampal formation from mid-gestation to the late postnatal period. Neuroscience 105,831-843. doi: 10.1016/S0306-4522(01)00156-7
96. Shichiri, M., Yoshida, Y., Ishida, N., Hagihara, Y., Iwahashi, H., Tamai, H., et al. (2011). Alpha-Tocopherol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome. Free Radic. Biol. Med. 50, 1801-1811. doi: 10.1016/j.freeradbiomed.2011.03.023
97. Sillitoe, R. V., and Joyner, A. L. (2007). Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu. Rev. Cell Dev. Biol. 23, 549-577. doi: 10.1146/annurev.cellbio.23.090506.123237
98. Stagni, F., Giacomini, A., Guidi, S., Ciani, E., Ragazzi, E., Filonzi, M., et al. (2015). Long-term effects of neonatal treatment with fluoxetine on cognitive performance in Ts65Dn mice. Neurobiol. Dis. 74C, 204-218. doi: 10.1016/j.nbd.2014.12.005
99. Stagni, F., Magistretti, J., Guidi, S., Ciani, E., Mangano, C., Calzà, L., et al. (2013). Pharmacotherapy with fluoxetine restores functional connectivity from the dentate gyrus to field CA3 in the Ts65Dn mouse model of Down syndrome. PLoS ONE 8:e61689. doi: 10.1371/journal.pone.0061689
100. Stagni, F., Trazzi, S., Giacomini, A., Guidi, S., Emili, M., Ciani, E., et al. (2014). Treatment with Epigallocatechin Gallate rescues neurogenesis and neuron maturation in the Ts65Dn mouse model of Down syndrome. XXII National Congress of the Italian Society of Psychophysiology. 27th-29th November 2014. Neuopsychological Trends. 16, 120.
101. Stiles, J., and Jernigan, T. L. (2010). The basics ofbrain development. Neuropsychol. Rev. 20, 327-348. doi: 10.1007/s11065-010-9148-4
102. Sudarov, A., and Joyner, A. L. (2007). Cerebellum morphogenesis: the foliation pattern is orchestrated by multi-cellular anchoring centers. Neural Dev. 2:26. doi: 10.1186/1749-8104-2-26
103. Takahashi, T., Nowakowski, R. S., and Caviness, V. S. Jr. (1996). The leaving or Q fraction of the murine cerebral proliferative epithelium: a general model of neocortical neuronogenesis. J. Neurosci. 16, 6183-6196.
104. Takashima, S., Ieshima, A., Nakamura, H., and Becker, L. E. (1989). Dendrites, dementia and the Down syndrome. Brain Dev. 11, 131-133. doi: 10.1016/S0387-7604(89)80082-8
105. Ten Donkelaar, H. J., Lammens, M., Wesseling, P., Thijssen, H. O., and Renier, W. O. (2003). Development and developmental disorders of the human cerebellum. J. Neurol. 250, 1025-1036. doi: 10.1007/s00415-003-0199-9
106. Toso, L., Cameroni, I., Roberson, R., Abebe, D., Bissell, S., and Spong, C. Y. (2008). Prevention of developmental delays in a Down syndrome mouse model. Obstet. Gynecol. 112, 1242-1251. doi: 10.1097/AOG.0b013e31818c91dc
107. Trazzi, S., Mitrugno, V. M., Valli, E., Fuchs, C., Rizzi, S., Guidi, S., et al. (2011). APP-dependent up-regulation of Ptch1 underlies proliferation impairment of neural precursors in Down syndrome. Hum. Mol. Genet. 20, 1560-1573. doi: 10.1093/hmg/ddr033
108. Vacca, R. A., and Valenti, D. (2015). Green tea EGCG plus fish oil omega-3 dietary supplements rescue mitochondrial dysfunctions and are safe in a Down's syndrome child. Clin. Nutr. 34, 783-784. doi: 10.1016/j.clnu.2015.04.012
109. Velazquez, R., Ash, J. A., Powers, B. E., Kelley, C. M., Strawderman, M., Luscher, Z. I., et al. (2013). Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiol. Dis. 58, 92-101. doi: 10.1016/j.nbd.2013.04.016
110. Vidal, V., García, S., Martínez, P., Corrales, A., Flórez, J., Rueda, N., et al. (2012).Lack of behavioral and cognitive effects of chronic ethosuximide and gabapentin treatment in the Ts65Dn mouse model of Down syndrome. Neuroscience 220, 158-168. doi: 10.1016/j.neuroscience.2012.06.031
111. Vink, J., Incerti, M., Toso, L., Roberson, R., Abebe, D., and Spong, C. Y. (2009). Prenatal NAP+SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and gamma-aminobutyric acid receptors. Am. J. Obstet. Gynecol. 200, e521-e524. doi: 10.1016/j.ajog.2009.01.052
112. Whitaker-Azmitia, P. M. (2001). Serotonin and brain development: role in human developmental diseases. Brain Res. Bull. 56, 479-485. doi: 10.1016/S0361-9230(01)00615-3
113. Xie, W., Ramakrishna, N., Wieraszko, A., and Hwang, Y. W. (2008). Promotion of neuronal plasticity by (-)-epigallocatechin-3-gallate. Neurochem. Res. 33, 776-783. doi: 10.1007/s11064-007-9494-7
114. Yan, Y., Jiang, X., West, A. A., Perry, C. A., Malysheva, O. V., Brenna, J. T., et al. (2013)Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women. Am. J. Clin. Nutr. 98, 1459-1467. doi: 10.3945/ajcn.113.066092