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

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