Table 9.

Fluoride concentrations of in vitro studies that caused positive results in neuronal cells and precursor/stem cells

Cell type	Fluoride concentrations		Endpoint	References
	Highest concentration without effect	Lowest concentration with effect
Neuro-2 A cells	2 mM	4 mM	Altered expression of neuronal genes	Chen et al. (2017a)
Human embryonic stem cells (H9)	0.5 mM	1 mM	Altered gene expression	Fu et al. (2016)
		2 mM	Cytotoxicity
Mouse embryonic stem cells (D3)		1 mM	Cytotoxicity	Nguyen Ngoc et al. (2012)
Primary hippocampal neurons of rats	0.48 mM	0.95 mM	Cytotoxicity	Zhang et al. (2007)
Primary hippocampal neurons of rats		0.48 mM	Olive tail moments elevated Up-regulation of NF-kappaB (p < 0.05) DNA damage	Zhang et al. (2008)
		0.95 mM	Increase of DNA in the tail Up-regulation of NF-kappaB (p > 0.05) S-phase cell-cycle arrest
Primary hippocampal neurons of rats		0.48 mM	NCAM-140 expression level decreased	Xia et al. (2007)
		0.95 mM	NCAM expression level decreased
		1.91 mM	NCAM-120 expression level decreased Cell survivor decreased
Primary hippocampal neurons of mouse		0.12 mM	Intracellular Ca2+ fluxes > increase of intercellular concentration Increase of apoptotic peaks	Haojun et al. (2012)
PC12 cells (pheochromocytoma cells)		0.5 mM	Cytotoxicity (8 h)	Ke et al. (2016)
		1 mM	Cytotoxicity (2 h) Increased expression levels of apoptosis-related proteins (p-elF, PARP) Increased expression levels of ERS-related protein XBP-A
PC 12 cells (pheochromocytoma cells)		0.005 mM	Intracellular ROS increase Apoptotic cells Cytotoxicity (48 h)	Zhang et al. (2015b)
		0.05 mM	Apoptotic cells Cytotoxicity (8 h)
		0.5 mM	Apoptotic cells Cytotoxicity (2 h)
PC 12 cells (pheochromocytoma cells)	0.024 mM	0.24 mM	Decline of MTT reduction Protein oxidation	Shan et al. (2004)
PC 12 cells (pheochromocytoma cells)	0.024 mM	0.24 mM	Selective decreases in the number of nAChRs	Chen et al. (2003)
PC 12 cells (pheochromocytoma cells)	0.024 mM	0.24 mM	Increase of total inositol phosphates	Bencherif and Lukas (1991)
BV-2 microglia cells	0.5 mM	1 mM	Increase of IL-6 concentration	Chen et al. (2017b)
		2 mM	Significant decrease of cell viability (12 h) SOD activity lower Increase of TNF-α level
BV-2 microglia cells	0.024 mM	0.119 mM	Increased JNK phosphorylation level	Yan et al. (2013)
		1.19 mM	Cytotoxicity Increase of NO release Increase of TNFα release
BV-2 microglia cells		0.024 mM	SOD activities decreased NOS (synthesizing NO) increased	Shuhua et al. (2012)
		0.119 mM	Change into activated microglia Up-regulated OX-42 expression
		1.19 mM	Cytotoxicity
Bergmann glia cells	0.5 mM	1 mM	Cytotoxicity	Flores-Mendez et al. (2014)
Hippocampal slices of rat and mouse		1 to about 5 mM	Activation of MAP kinase Followed by volume reduction	Lee et al. (2016)
Astrocytes of rat cerebral cortex		1 mM	Cell cycle arrest transited from S phase to G2/M phase Increase of subG1 cells	Li et al. (2010)
Human neuroblastoma SH-SY5 Y cells		0.48 mM	Drp1 expression increased Fis 1 expression reduced Mfn1 protein increased Mfn2 protein increased	Zhao et al. (2019)
		0.95 mM	Drp1 expression reduced Fis 1 expression reduced Mfn1 expression increased Mfn2 expression increased
Human neuroblastoma SH-SY5 Y cells	0.71 mM	0.95 mM	Cytotoxicity Induced apoptosis	Tu et al. (2018)
Human neuroblastoma SH-SY5 Y cells	0.48 mM	0.95 mM	SYN expression reduced TrkB expression reduced p-Erk expression increased	Chen et al. (2018a, b)
		1.43 mM	PSD 95 protein expression reduced BDNF protein expression increased
Human neuroblastoma SH-SY5 Y cells	0.48 mM	0.95 mM	Autophagic vesicles decreased	Tang et al. (2017)
Human neuroblastoma SH-SY5 Y cells	0.48 mM	0.95 mM	LDH levels higher	Xu et al. (2013)
Human neuroblastoma SH-SY5 Y cells	0.48 mM	0.95 mM	Cytotoxicity Percentages of apoptosis higher Activity of caspase-3 higher mRNA expression levels for Fas, Fas-L, and caspases (3 and 8) higher	Xu et al. (2011)
Human neuroblastoma SH-SY5 Y cells		0.12 mM	Cytotoxicity (24 h) Expression of phospho-JNK	Liu et al. (2011)
		1.91 mM	Cytotoxicity (8 h) MTT reduction
Human neuroblastoma SK-N-SH cells		~ 2.5 mM	Stimulation of inositol phosphates release	Fisher et al. (1993)