Review Article

Molecular and Cellular Alterations in Down Syndrome: Toward the Identification of Targets for Therapeutics

Table 1

Significant quantitative transcript variations observed in the DS mouse models (trisomics and transgenics, see Figure 1). Results are classified from top to bottom with increasing age of the mice studied: age in embryonic days (E), postnatal days (d) and month (m). Names in bold for genes present in 2 copies. Transcriptome methods used: C (cDNA arrays); N (Northern); M (microarrays); Q (quantitative-RT-PCR); R (RT-PCR). Gene names are indicated according to gene nomenclature (Gene Cards: http://www.genecards.org/).

Brain structuresModelsAgeUpDownMethodAdditional commentTargetRescueReferences

E11–E13 telencephalon, mesencephalon + diencephalonTgYAC152F7E11.5, E12.5, E13.5Dyrk1aQ, M Dysregulation of the Rest pathway[37]

Embryonic, brain hemispheres, cerebellumTs1Cje; TgPCP4E11.5, E14.5, 4 mPcp4Q[38]

Embryonic totalTc1E14.5–-RExpression human genes[32]

EmbryonicmBACTgDyrk1aE14.5Dyrk1AQ[25]

Total brainTs1Cjebirthmean: 1.435M[39]

CerebellumTs1CjebirthPtch, ShhM[26]

Cortex, brainTs65Dn8 dVip, Vipr1Q[40]

Total brainTs65Dn1 m62% of 3-copy genesQ[18]

Hippocampus, frontal cortex, substantia nigraTs65Dn78–92 dKcnj6Q[41]

HippocampusTgYAC152F73 mDyrk1aBdnf, TrkbQDyrk1aBdnf, Trkb[42]

HippocampusTS65Dn3 m Gart, Ifnar2, Kcnj6, Itsn1, Hcls, Sod1MGabra5Bdnf[43]

CerebellumTs65Dn3-4 mrange (0.84–2.93); mean 1.45M[44]

Cortex, midbrain, cerebellumTs65Dn4 mmean: 1.63, 1.3, 1.37C, M[17]

ForebrainTs65Dn4 mApp, Sod1, ApoEN[45]

Hippocampus (rescue), prefrontal cortexTs65Dn5-6 mmir155, mir802, Mef2cCreb1, Mecp2Qmir-155, mir-802Mecp2, Mef2c, Creb1[46]

Brain hemispheresTs65Dn4 to 12 m App, Sod1, Dyrk1aQincrease with age[21]

BrainTs65Dn6-7 mGfapQ[47]

Hippocampus, cortex, raphe nucleiTs65Dn9.5 mVip, Vipr1Q[48]

HippocampusTs65Dn10 mBdnfQNmdarBdnf[49]

Total brainTs65Dn11 m47% of 3-copy genesQ[18]

Hippocampal CA1Ts65Dn (m + f)12–24 mHtr2cCdk5, Ntf3Q[50]

Medial septum, hippocampusTs65Dn18 mAppQ[51]