In vitro dopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Figures & data

Figure 1. Schematic overview of neurotransmission between a presynaptic (left) and postsynaptic (right) cell. AP: action potential, VMAT: vesicular monoamine transporter, VGCC: voltage-gated calcium channel, DAT: (membrane) dopamine transporter.

Figure 2. Schematic view of the mesocortical, mesolimbic and nigrostriatal dopaminergic pathways in the human brain (modified from http://www.peoi.org chapter 8, section B).

Figure 3. Schematic representation of channels and receptors in the cell membrane and the membranes of intracellular stores implicated in maintenance of the intracellular calcium homeostasis. NCX: Na⁺/Ca²⁺ exchanger, NT: neurotransmitter receptor, PMCA: plasma membrane Ca²⁺-ATPase, VGCC: voltage-gated calcium channel, RyR: ryanodine receptor, SERCA: sarco/endoplasmic reticulum Ca²⁺-ATPase, InsP₃R: inositol triphosphate receptor, MNCX: mitochondrial Na⁺/Ca²⁺ exchanger.

Table 1. Human exposure data.

Lindane
Population	Tissue/medium	Median/max	Value	Unit	Corresponding conc. (nM)	Reference
Adults (GB)	serum	median	16	ng/g l.w.	0.6	Thomas et al. (2006)
		95th percentile	110		4.2
Adults (PT)	serum	mean	0.7	ng/ml serum	1.3	Cruz et al. (2003)
		max	7.5		14
Young men (ES)	serum	median	1.2	ng/ml serum	2.2	Carreño et al. (2007)
		95th percentile	17.7		33
Children (MX)	serum	median	2543	ng/g l.w.	97	Trejo-Acevedo et al. (2009)
		95th percentile	8186		360
Women (ES)	cord blood	mean	3.9	ng/ml serum	7.5	Jimenez-Torres et al. (2006)
		95th percentile	108.6		210
Women (ES)	serum	mean	1.3	ng/ml serum	2.4	Jimenez-Torres et al. (2006)
		95th percentile	4.4		8.3
Adult women (ES)	serum	mean	1.5	ng/ml serum	2.9	Botella et al. (2004)
		95th percentile	12.8		24
Adult women (BE)	serum	median	1.6	ng/g l.w.	0.06	Koppen et al. (2002)
		95th percentile	8.1		0.3
Women (SK)	breast milk	median	15	ng/g l.w.	2.2	Prachar et al. (1993)
		max	106		15
Women (RO)	breast milk	mean	161	ng/g l.w.	23	Dirtu et al. (2006)
Dieldrin
Population	Tissue/medium	Median/max	Value	Unit	Corresponding conc. (nM)	Reference
Adults (US)	serum	min	1.2	ng/g l.w.	0.04	Xu et al. (2010)
		max	670		20
Women (ES)	serum	mean	4	ng/ml serum	6.1	Rivas et al. (2007)
		max	28		41
Women	serum (cord)	max	0.3	ng/ml serum	0.4	Butler Walker et al. (2003)
(arctic CA)	serum (maternal)	max	1		1.4
Women (IN)	blood (cord)	max	4.7	ng/ml	6.9	Mustafa et al. (2010)
	blood (maternal)	max	4.5		6.5
Women (IN)	breast milk	median	20	ng/g l.w.	2.2	Subramanian et al. (2007)
		max	4500		490
Children (ES)	adipose tissue	median	130	ng/g l.w.	270	Lopez-Espinosa et al. (2008)
		max	3440		7200
DNOC
Population	Tissue/medium	Median/max	Value	Unit	Corresponding conc. (μM)	Reference
Healthy volunteers* (US)	blood	min	15	μg/g	76	Harvey et al. (1951)
		peak	48		240
Agricultural workers (NL)	serum	min	11	μg/ml	31	van Noort et al. (1960)
		max	88		240
Agricultural workers (NL)	blood	min	0.6	μg/g	3	Heuts (1993)
		max	0.8		4

* 1 mg/kg for seven days.

Table 2. In vitro effect concentrations.

	Compound	Target	Measure	Effect conc. (μM)	Reference
Organochlorine insecticide	Lindane	basal [Ca2+]i	LOEC	10	Heusinkveld et al. (2010)
		VGCC	LOEC	3
			EC50	1
	Dieldrin	VGCC	LOEC	0,1*	Heusinkveld and Westerink (2012)
			EC50	0.13
Azole fungicides	Imazalil	VGCC	LOEC	3	Heusinkveld et al. (2013)
			EC50	7.5
	Flusilazole	VGCC	LOEC	1	Heusinkveld et al. (2013)
			EC50	5.1
	Tebuconazole	VGCC	LOEC	3	Heusinkveld et al. (2013)
			EC50	11
	Triadimefon	VGCC	LOEC	1	Heusinkveld et al. (2013)
			EC50	37.2
	Cyproconazole	VGCC	LOEC	30	Heusinkveld et al. (2013)
			EC50	65
Dinitrophenol herbicide	DNOC	GABA-R	LOEC	10	Heusinkveld et al. (unpublished observations)
		basal [Ca2+]i	LOEC	10
		alpha-synuclein	LOEC	1
	Dinoseb	GABA-R	LOEC	10	Heusinkveld et al. (unpublished observations)
		basal [Ca2+]i	LOEC	1
		alpha-synuclein	LOEC	0.3

*Following 20 min exposure.

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