. Author manuscript; available in PMC: 2023 Jun 1.

Published in final edited form as: Ageing Res Rev. 2022 Apr 29;78:101636. doi: 10.1016/j.arr.2022.101636

Table 1-. Summary of studies on the changes of neurogenesis in animal models of neurodegenerative diseases.

Here we summarized previous studies on the changes of neurogenesis in both SGZ and SVZ in animal models of neurodegenerative disorders, including the type of animal model, investigated area and markers used in studies, as well as the details of phenotypes related to neurogenesis. Altered neurogenesis was found in most of these animal models, which may contribute to the etiology involved in neurodegenerative diseases.

Disease	Organism	gene	Area	Change in neurogenesis	Markers	Age(month)	Features related to neurogenesis	Refs
AD	Mouse	APP_{S w,Ind}	SGZ	↑	BrdU, Ki67, PSA-NCAM, β-tubulin III	3	Increased BrdU⁺, Ki67⁺ cells by increased neuronal differentiation labeled by PSA-NCAM⁺, β-tubulin III⁺ cells;	(López-Toledano and Shelanski, 2007)
		APP_{S w,Ind}	SGZ	↓	BrdU, Ki67, PSA-NCAM, β-tubulin III	5, 9, 11	Reduced neurogenesis started at 5-month-old and persisted at 9- and 11 month-old.	(López-Toledano and Shelanski, 2007)
		APP	SGZ	N.C.	DCX, MCM2, NF68	8–9, 18–24	No change in DCX⁺ cells	(Zhang et al., 2007)
		PS1	SGZ	↓			A small decrease in DCX⁺ cells
		APP, PS-1	SGZ	↓			Reduced by 60% and in an age dependent way
		APPswe, PS1-dE9	SGZ	↑	BrdU, DCX	3, 9	The memory and hippocampal proliferation were not affected at 3-month-old; Memory impairment, increased Aβ deposits, and	(Yu et al., 2009)
Disease	Organism	gene	Area	Change in neurogenesis	markers	Age (month)	Features related to neurogenesis	Refs
AD	Mouse	APP, PS1, nestin-GFP	SGZ	↓	nestin-GFP DCX BrdU GFAP	7d, 1, 3, 7	BrdU⁺-, DCX⁺- and GFAP⁺- Nestin-GFP⁺ cells decreased started from 3 month-old. Abnormal morphologies of dendrites in SGZ;	(Zeng et al., 2016)
		APP, PS1, nestin-GFP	SVZ	N.C.	nestin-GFP DCX BrdU GFAP	7d, 1, 3, 7	The number of nestin-GFP⁺ cells decrease	(Zeng et al., 2016)
		PS1HWT	SGZ and SVZ	N.C.	BrdU	2	No change in BrdU⁺ and DCX⁺ cells	(Demars et al., 2010)
		APPs we, PS1ΔE9	SGZ	↓	BrdU DCX	2	Reduced as early as 2 month-old; impaired proliferation and tau hyperphosphorylation exhibited in neurospheres isolated from APPswe/PS1ΔE9 mice
		APPs we, PS1ΔE9	SVZ	↓	BrdU DCX	2
AD	Mouse and NPCs	APPswe, PS1ΔE9	SGZ	-	EdU	4	Transplantation of human NPC reduced Aβ load and increased microglia within hippocampal and cortical regions; Improve hippocampal dependent cognition	(McGinley et al., 2018)
Disease	Organism	gene	Area	Change in neurogenesis	markers	Age (month)	Features related to neurogenesis	Refs
AD	Mouse and NPCs	APP_KM670/671NL	SVZ	↓	BrdU, DCX, SOX2, GFAP	1.5	Decreased OB neurogenesis and fewer Calretinin⁺ interneurons in OB; Smaller neuron size; More DCX⁺ neuroblasts and fewer Sox2⁺ progenitors	(Scopa et al., 2020)
	Mouse and NPCs	Aβ	SGZ	↓	GFAP, Ki67, CD44, CD90, CD34, CD45	1.5	Aβ-treated NPCs decreased the expression of Ki67, GFAP, SOX2, and Nestin by suppressing the Wnt signaling pathway	(Oh et al., 2015)
	Rat	Aβ	SGZ	-	-	P5,P7,P15,P25	Aβ trigger spine loss by partially inhibiting NMDARs	(Shankar et al., 2007)
	Mouse	MAPT	SGZ	↓	DCX, Ki67	2, 6, 12	Decreased Dcx-NeuN⁺ cells as early as 2 months of age in both SGZ and SVZ; Decreased Ki67⁺ cells in SVZ with aging	(Komuro et al., 2015)
			SVZ	↓	DCX, Ki67	2, 6, 12		(Komuro et al., 2015)
			-	-	-	6	Aging-dependent short-term memory deficits, hyperactivity and synaptic plasticity defects	(Biundo et al., 2018)
Disease	Organism	gene	Area	Change in neurogenesis	Markers	Age (month)	Features related to neurogenesis	Refs
AD	Mouse	Tau Tg30	SGZ	↓	DCX, Ki67, GFAP	12	DCX⁺ and Ki67⁺ cells decreased in Tg30 mice but not in Tg30/tau KO mice; GFAP⁺ cells showed no difference between Tg30 and Tg30/tau KO mice	(Houben et al., 2019)
		Tg30/TauKO	SGZ	↓	DCX, Ki67, GFAP	12		(Houben et al., 2019)
		APPswe, PS1_M146V, MAPT_P301L	SGZ	↓	HH3	2–4, 6, 9, 12	The age-associated reduction was more significant in female mice; More related to dorsal than ventral hippocampus	(Rodríguez et al., 2008)
		APPswe, PS1_M146, MAPT_P301L, Polβ	SGZ	↓	BrdU	6, 14	No change in hippocampal volume and adult neurogenesis at 6 months, but reduced at 14 months; Impaired memory and synaptic plasticity in 3xTg/Pol β^+/− mice	(Sykora et al., 2015)
		5xFAD	SGZ	↓	DCX, HH3, calretinin	2–4, 7	The number of DCX⁺, HH3⁺, and calretinin ⁺ cells decreased in 5xFAD hippocampus;	(Moon et al., 2014)
Disease	Organism	gene	Area	Change in neurogenesis	label	Age (month)	Features related to neurogenesis	Refs
AD	Mouse	5xFAD	SGZ	↓	Ki67, DCX, SOX1, SOX2, SOX21	2	SOX1⁺ and SOX21⁺ cells decreased in AD mice; DCX⁺ cells decreased only in male AD mice; SOX2⁺ cells decreased only in female AD mice; No change in the Ki67⁺ cells in both gender; The protein levels of BDNF were not affected in the 5xFAD mice	(Zalet el et al., 2018)
		5xFAD	SGZ	↓	DCX	10	Reduced neuron numbers and neurogenesis both in males and females; Restored by overexpression of VGF, a nerve growth factor	(Beckmann et al., 2020)
		PS1	ventricular zone	↓	BrdU	E11.5	Premature differentiation of NPCs, which leading to early depletion of the neural progenitor population	(Yang et al., 2000)
		PS2		N.C.	DCX, Ki67	1.5–2	Deletion of PS2 does not affect hippocampal adult neurogenesis	(Dhaliwal et al., 2018)
Disease	Organism	gene	Area	Change in neurogenesis	label	Age (month)	Features related to neurogenesis	Refs
AD	mouse	APOE ε3/APOE ε4	SGZ	↓	Nestin, SOX2, BrdU, GFA P	3, 6–7, 12–13	Neurogenesis reduced but astrogenesis increased in APOE-KO Mice; Increased BMP signaling promoted glial differentiation at the expense of neurogenesis in APOE ε4 mice, Presynaptic GABAergic input-mediated maturation of newborn neurons was diminished in APOE ε4 mice	(Li et al., 2009)
		APOE ε3/APOE ε4	SVZ	↓	Nestin, SOX2, BrdU, GFA P	3, 6–7, 12–13		(Li et al., 2009)
		GFAP-APOE	SGZ	↓	BrdU, GFAP	2	Reduced APOE after injury; The injury-induced proliferation of hippocampal neural progenitors is absent in APOE-deficient mice; GFAP-ApoE4 mice decreased neurogenesis after injury.	(Hong et al., 2016)
		nestin-APOE	SGZ	↓	DCX	1, 2, 9	An overall decrease in type 1 Nestin- and GFAP-expressing neural stem cells	(Yang et al., 2011)
		GFAP-APOE	SGZ	N.C.	synaptophsin, NSE, GFAP	6, 10, 14	Impaired learning and working memory; Increased activity and anxiety; no alterations of the expression synaptophysin, NSE, GFAP	(Hartman et al., 2001)
Disease	Organism	gene	Area	Change in neurogenesis	label	Age (month)	Features related to neurogenesis	Refs
A-T	Mouse and NPCs	ATM	-	-	Ki67, GFAP	3	No change in the number of proliferating cells; Resistance to apoptosis after irradiation	(Barazzuol et al., 2017)
	Mouse		SGZ	↑	Ki67, EdU, cyclin A, PCNA	2, 3	Neurons loss in hippocampus and frontal cortex; Cyclin A⁺ and PCNA⁺ cells were significantly elevated	(Shen et al., 2016)
	Mouse		SGZ	↓	BrdU	1, 2	ATM down regulated during cells differentiate; Decreased proliferation and survival of NPCs and genomic instability	(Allen et al., 2001)
PD	C. elegans	SNCA	-	↓	-	-	Neuronal and dendritic loss in dopaminergic neurons but not with a motor neuron promoter	(Lakso et al., 2003)
	Mouse	SNCA	SVZ	↓	PCNA, DCX+ BrdU	5, 15	Decreased number of PCNA⁺, DCX⁺ and BrdU⁺ cells and increase in TUNEL⁺ cells in OB	(Winner et al., 2008)
		Lrrk2	SGZ	↓	DCX, BrdU	4	Decreased proliferation both in SGZ and SVZ Neurite outgrowth and spine numbers reduced in new neurons in DG	(Winner et al., 2011)
		Lrrk2	SVZ	↓	DCX, BrdU	4		(Winner et al., 2011)
Disease	Organism	gene	Area	Change in neurogenesis	label	Age(month)	Features related to neurogenesis	Refs
PD	Mouse and NPCs	PINK1 (PARK6)	SGZ	↓	DCX, SOX2	3	Decreased proliferation and TMRE/Mi toTracker Green ratio; Reduced maximum OCR, spare respiratory capacity and growth; Increased apoptosis in PINK1^−/− NSCs; Abnorma l morpholo gic features of PINK1^−/− DCX⁺ neurons	(Agnihotri et al., 2017)
	Mouse and NPCs	Parkin (PARK2)	SVZ	↓	GFAP	E15	Arrested neuronal differentiation and abnormal morphology of NPCs; Decreased GFAP⁺ cells	(Park et al., 2017)
	Rat	SNCA	SGZ	↓	BrdU	4	Reduced survival of BrdU⁺ cells in DG, while proliferation not be affected	(Kohl et al., 2016)
CS	Human iPSC	CSB	-	↓	PAX6, OCT4, SOX2	-	Reduced differentiation potential and proliferati on	(Vessoni et al., 2016)
CS	Mouse	CSB	SGZ	N.C.	BrdU	E14.5, 4	Neural progenitors were not affected but showed defective self-renewal	(Sacco et al., 2013)

Abbreviations: ↑, increase; ↓, decrease; Aβ, amyloid beta; AD, Alzheimer’s disease; APOE, apolipoprotein E; APP, amyloid precursor protein; A-T, Ataxia Telangiectasia; ATM, Ataxia Telangiectasia mutated; BDNF, brain-derived neurotrophic factor; BrdU, Bromodeoxyuridine; DCX, Doublecortin; DG, dentate gyrus; E, embryo; NSC, neural stem cell; OB, olfactory bulb; P, postnatal day; PCNA, proliferating cell nuclear antigen; PD, Parkinson’s disease; Polβ, DNA polymerase β; PS1, presenilin 1; PS2, presenilin 2: SGZ, subgranular zone; SNCA, synuclein alpha; SOX2, sex determining region Y-box 2; SVZ, subventricular zone