Table 1.

Manipulations of the CXCL12 signaling pathway and associated effects on neurogenesis and/or neurodegenerative disorders in animal models^a

Mouse model	Treatment/Manipulation	Effects on CXCL12-CXCR4 axis	Pathology/phenotype	Regions	Diseases	Refs
WT	CXCR4 antagonist AMD3100	↓	Blockage of CXCR4 directly impairs learning and memory	Hippocampus	AD	[100]
	CXCL12	↑	Intracranial injection of CXCL12 enhances neurogenesis and memory	Hippocampus	AD	[105]
Demyelination/MS models
JHMV		↑	Pathologically-induced CXCL12 enhances migration, proliferation, and differentiation of the cells into OPCs	Spinal cord	MS	[96]
	CXCL12 antibody	↓	Antibody internalization of CXCL12 impairs migration and proliferation of engrafted stem cells	Spinal cord	MS	[96]
	CXCR4 antagonist AMD3100	↓	Inhibiting CXCR4 impairs migration and proliferation of engrafted stem cells	Spinal cord	MS	[96]
Cuprizone		↑ CXCL12	Induced CXCL12 enhances migration and proliferation of OPCs	CC, brain	MS	[95]
	CXCR4 KD		KD of CXCR4 decreases OPCs maturation and impairs the remyelination in the lesion sites	CC, brain	MS	[95]
	CXCR4 antagonist AMD3100		Inhibiting CXCR4 decreases OPCs maturation and impairs the remyelination in the lesion sites	CC, brain	MS	[95]
AD models
Tg2576		↓	Down-regulated CXCL12 is related to the impaired learning and memory	DG, Hippocampus	AD	[100]
	Exercise	↑	Exercising up-regulated CXCL12, which is associated with improved learning and memory	DG, Hippocampus	AD	[103]

^aAbbreviations: AD, Alzheimer’s disease; APP, amyloid Precursor Protein; CC, Corpus callosum; DG, dentate gyrus ; JHMV, JHM strain of mouse hepatitis virus; KD, knockdown; MS, multiple sclerosis; Tg2576. APP “Swedish mutation” transgenic mice; WT, wild-type mice.