Table 2.
Molecular changes observed in DS mouse models: Proteome.
| Brain structures | Models | Age | Up | Down | Method | Additional comment | Treatment | Target | Rescue | References |
|---|---|---|---|---|---|---|---|---|---|---|
| Embryo E11; E14 SNC | Ts1Cje; TgPCP4 | E11; E14 | Pcp4, Tubb3, Map2c; Calb2 | W, I | [38] | |||||
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| Neonatal brain | Ts65Dn | P0 | Map2, Ntf3 | Syp | W, I | [71] | ||||
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| Cortex | mBACTgDyrk1a | P0 | Dyrk1a, Gap43 | W | [25] | |||||
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| Hippocampus | Ts65Dn | P2 | Ptch1 | I | [72] | |||||
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| Hippocampus | Ts65Dn | P25 | Kcnj6 | Gabbr2 | W | [73] | ||||
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| Medial septum | Ts65Dn | P2–20 m | p75Ngfr (6 m) | I | [45] | |||||
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| Thalamus, medulla oblongata | Ts65Dn | 1 m | Gabbr2 | W | [74] | |||||
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| Hippocampus | Ts65Dn | 15–45 d | neuron, glia | I | fluoxetine | neurogenesis | [75] | |||
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| Brain | Ts65Dn | 49–66 d | KIF17 | W | involv. NR2B transport | [76] | ||||
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| Hippocampus | Ts65Dn | 2–4 m | P (CaMKIIa, AKT), Glur1, p(Ser831)- Glur1 | pERK | W | [77] | ||||
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| Hippocampus, frontal cortex | Ts65Dn | 80 d | Kcnj6, Kcnj3 | W | [41] | |||||
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| Brain | Ts65Dn | 3–5 m | App, Synj1 | W | [54] | |||||
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| Brain | TgSYNJ1 | 3–5 m | Synj1 | W | [54] | |||||
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| Cortex | mBACTgDyrk1a | 3 m | Dyrk1A, Ccnd1, Syp, Map2 | W | [25] | |||||
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| Hippocampus | Ts65Dn | 1 m, 4 m, 12 m | App (12 m) | W | RS86 (agonist) | Chrm1 | App increase (12 m) in Ts and 2N | [78] | ||
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| Basal forebrain, hippocampus, paraventricular nucleus | Ts65Dn | 3 m | Nos1 in MSN, DB, PVN | I | [79] | |||||
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| Brain | Ts65Dn, TgSYNJ1 | 3–5 m | PtdInsP | Ptdlns (4, 5)P2 | E | Synj1 gene copy | yes | [54] | ||
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| Hippocampus | Ts65Dn | 4 m | Ntf3, Cdk5 | Syp | W | [71] | ||||
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| Brain, hippocampus, cortex, striatum | Ts65Dn | 4–12 m | App, Sod1, Dyrk1A, sAPP-alpha and -beta (12 m) | W | [21] | |||||
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| Brain hemispheres, cerebellum | Ts1Cje; TgPCP4 | 4 m | Pcp4 | W, I | [38] | |||||
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| Somatosensory cortex | Ts65Dn | 4-5 m | Syp, Gad67, Calb, Calb2, Parv | I | [80] | |||||
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| Brain hemispheres | Ts65Dn | 5–12 m | increase with age: App, Sod1 | W | [21] | |||||
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| Hippocampus (rescue), prefrontal cortex | Ts65Dn | 5-6 m | Mef2c | Creb1, Mecp2 | W | [46] | ||||
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| BFCN, hippocampus | Ts65Dn, Ts1Cje | 6 m, 12 m | App, Vchat hipp. termini | Ngf transport | W, I | App copy numb. dep. | [81] | |||
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| Hippocampus | Ts65Dn | 7-8 m | Tiam1, Dyrk1a | W | MK801 ip | Nmdar | no | [52] | ||
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| Cortex | Ts65Dn | 7-8 m | Tiam1, Itsn1, Dyrk1A, p(AKT, ERK, GSK3b) | W | MK801 ip | Nmdar | Dyrk1a, pERK1, 2 | [52] | ||
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| Hippocampus | Ts1Cje | 7-8 m | Dyrk1a; pERK1,2 | W | MK801 ip | Nmdar | Dyrk1a; pERK 1, 2 | [52] | ||
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| Cortex | Ts1Cje | 7-8 m | Itsn1, Dyrk1a, p(AKT, ERK, GSK3b) | W | MK801 ip | Nmdar | Dyrk1a | [52] | ||
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| Medial septum, hippocampus | Ts65Dn ( m + f) | 7–18 m | microglia (CD45+) | Calb1 (hippo) | I | minocycline (7–10 m) | inflammation | CD45, Calb1 | [82] | |
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| Hippocampus, medial septum, locus coerelus | Ts65Dn | 10 m | Calb1 (H), Chat (MS), Th (LC) | I | memantine (4–10 m) | Nmdar | no | [49] | ||
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| Hippocampus, olfactory bulb, frontal cortex, cerebellum | Ts65Dn | 10–19 m | Chat (10 m, all ages in cerebellum), Glul (19 m) | Chat in medial septum, AChe | A | [83] | ||||
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| Medial septum BFCN | Ts65Dn | 12 m | p75Ngfr | I | [84] | |||||
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| Hippocampus | Ts65Dn | 12 m | Chat | A | [78] | |||||
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| Medial septum | Ts65Dn | 12 m | Chat | I | [78] | |||||
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| Cerebellum | Ts65Dn | 10–12 m | Gfap, Sap/Jnk activation | I, W | axonal damage | [85, 86] | ||||
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| Hippocampus, cingulate cortex | Ts65Dn/Ts1Cje | 12–15 m | Map2/ no | I | [87] | |||||
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| Medial septum | Ts65Dn | 18 m | Chat | I | Ngf infusion | Ngf transport | number and size | [84] | ||
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| Fronto-parietal cortex, hippocampus | Ts65Dn | 19 m | Gfap | W | [83] | |||||
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| Hippocampus, frontal cortex | TghAPP | 24 m | Abeta 42, UPS | alpha-, beta-secretase, Ngf | E | RS86 (agonist) | Chrm1 | Ngf, Abeta 42 increase (no) | [88] | |