Epigenetics in neurodegenerative disorders induced by pesticides

Yu, Guangxia; Su, Qianqian; Chen, Yao; Wu, Lingyan; Wu, Siying; Li, Huangyuan

doi:10.1186/s41021-021-00224-z

Genes and Environment

Table 1 Summary of epigenetic changes induced by pesticisdes

From: Epigenetics in neurodegenerative disorders induced by pesticides

Pesticides	Model	Exposure route	Exposure dose	Exposure length	Neurological damage	Epigenetic change	Ref.
Insecticides
Chlorpyrifos	Long Evans rats	Subcutaneous injection	3 or 10 mg/kg	21 days	Associated with problems in cognitive function.	MiR-132 and miR-212 in the CPF-exposed rat hippocampus were up-regulated.	[32]
Chlorpyrifos	SH-SY5Y cells	Cell culture	0, 25, 50, 100, and 200 μM	24 h	Cell viability was decreased. Pyroptosis related proteins, ROS levels, as well as level of caspase-1 and the TUNEL positive cells were all significantly up-regulated.	Expression of miR-181 was enhanced.	[33]
Chlorpyrifos-oxon	Zebrafish	Embryonic exposure	0.01 and 50 μg/L	4–120 h post fertilization	Even low dose exposures can have transgenerational effects in neurological activity.	Induce alterations in global DNA methylation.	[34]
Dieldrin	C57BL/6 mice	Oral intake	0.3 mg/kg/3 days	30 days	Induce impairment of dopaminergic neuron development and maintenance.	Dieldrin-induced differential methylation was sex-specific.	[35]
Dieldrin	C57BL/6 J mice	Intraperitoneal injection	5.0 mg/kg every other day	30 days	Induce apoptotic cell death in dopaminergic neuronal Cells.	Induce a time-dependent increase in the acetylation of core histones H3 and H4.	[36]
Permethrin	Wistar rats	Oral intake	34.05 mg/kg	From PND6 to PND21	Early life permethrin exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) during neonatal brain development leads to its accumulation long after exposure.	DNMT1, DNMT3a were increased. The aggregation of DNMT3b and α-synuclein was enhanced.	[37].
	Wistar rats	Oral intake	34.05 mg/kg	From PND6 to PND21	Low dosage exposure to permethrin during neonatal brain development leads to dopamine decrease in rat striatum nucleus, oxidative stress and behavioural changes linked to the development of Parkinson’s like neurodegeneration later in life.	Global 5mC and 5hmC levels were increased. Methylation levels at H3K9me3 position at both Th and Nurr1 promoter regions were reduced.	[38]
	Wistar rats	Oral intake	34.05 mg/kg	From PND6 to PND21	An intergenerational permethrin-induced damage on progenies has been identified.	Global genome-wide DNA methylation was decreased in mothers exposed in early life to permethrin as well as in their offspring.	[39]
	Wistar rats	Oral intake	34.05 mg/kg	From PND6 to PND21	Parental exposure leads to a significant reduction in dopamine level in the offspring (F1) born from parents or just mothers early-life treated.	Early-life exposure to the stressor is associated with changes in global DNA methylation and hydroxymethylation in adult age.	[40]
Paraquat	N27 dopaminergic cells	Cell culture	400 mM	12, 24 or 36 h.	Cell culture models of Parkinson’s disease.	Histone H3 acetylation was induced in a time dependent manner.	[41]
	hNPCs	Cell culture	0, 5, 10, 20, 40, or 80 μM	24 h	Induce developmental neurotoxicity.	Induced differentially miRNAs expression.	[42]
	hNPCs	Cell culture	10 and 100 μM	24 h	Lead to the alteration of several neurodevelopment related key biological processes and crucial pathways.	Alter mRNAs and miRNAs expression.	[43]
	hNPCs	Cell culture	0, 25, 50 and 100 μM	24 h	PQ dramatically suppressed neural cell differentiation ability.	Direct binding effect between CTNNB1 and miR-200a existed following PQ exposure.	[44]
	Neuro-2a cells	Cell culture	100 μM	48 h	CaM and p21 were involved in PQ-induced toxicity.	Nrf2-regulated miR-380-3p inhibited cell proliferation and enhanced the PQ-induced toxicity in N2a cells potentially by blocking the translation Sp3 mRNA.	[45]
	SH-SY5Y cells	Cell culture	50 μM	24 h	Impairs Nrf2/ARE defense network.	Cause miR153 to bind to and target Nrf2 3′ UTR thereby weakening the cellular antioxidant Defense.	[46]
	Neuro-2a cells	Cell culture	300	48 h	Cell culture models of Parkinson’s disease.	The expression of miR-17-5p was downregulated, DNA methylation level was upregulated after PQ exposure.	[17]
	Neuro-2a cells	Cell culture	300	48 h	Induce Parkinson’s disease pathology.	The miR-17-5p was expressed at lower levels in PQ-treated Neuron-2a cells, overexpression of miR17-5p in Neuro-2a cells could enhance cell proliferation, suppresse apoptosis and promote S phase transition of the cell cycle after PQ treatment.	[47]
	ICR mice	Intraperitoneal injection	5, 10 mg/kg/2 days	10 times	Animal models of Parkinson’s disease.	PQ caused lncRNA expression profiling alteration in the substantia nigra (SN) through an interaction with Nrf2, thus changing the NR_027648/Zc3h14/Cybb and NR_030777/Zfp326/Cpne5 mRNA pathways.	[48]
	ICR mice	Intraperitoneal injection	5 mg/kg/3 days, 10 mg/kg/2 days,	10 times	Inhibited microglia and dopaminergic cells proliferation and microglia migration.	PQ-induced low expression of AK039862 rescued microglia proliferation and migration inhibition via the AK039862/Pafah1b1/Foxa1 pathway, AK039862 also participated in the interaction between microglia and dopaminergic cells with PQ treatment.	[49]
	BV2 cells and MN9d cells	Co-culture	0, 50, 100, 150 μM	36 h			[49]
	Neuro-2a cells	Cell culture	100, 300 μM	24, 36 h	Induce neurotoxicity	LncRNA NR_030777 has a vital protective role by regulating the expression of Zfp326 and Cpne 5 in neurotoxicity induced by PQ.	[50]
	MN9D cells
	Primary cortical neuron
	Neuro-2a cells	Cell culture	200 μM	3 h	Induce oxidative stress	m⁶A participated in a specific regulatory network of circRNAs to modulate the expression of downstream genes in response to PQ-induced oxidative stress	[51]
Avermectin	Pigeons	Oral intake	20, 40, 60 mg/kg	30, 60, 90 days	AVM exhibits significant cytotoxicity in pigeon brain nerve cells.	Global DNA hypomethylation and down-regulation of DNMT mRNA expression occurred in a dose-time-dependent manner in pigeon brains.	[52]
Fipronil	Zebrafish	Embryonic exposure	40 μg/L	From 6 to 96 h post fertilization	R-fipronil exhibited more intense neurotoxicity compared with S-fipronil.	The fipronil-conducted enantioselective neurotoxicity likely applied its enantioselectivity by the dysregulation of DNA methylation.	[53]
Atrazine (ATR)	Carp	Embryonic exposure	4.28, 42.8 and 428 μg/L	40 days	Not mentioned.	The MBD2 mRNA expression was up-regulated in the brain, the DNMTs mRNA expression was down-regulated	[54]
Chlorpyrifos (CPF)			1.16, 11.6 and 116 μg/L
Combined ATR/CPF			1.13, 11.3 and 113 μg/L
Deltamethrin	C57BL/6 N mice	Oral intake	3 mg/kg	During gestation, lactation, and weaning at postnatal day (PND) 21	Deltamethrin insecticide and stress exposure during neurodevelopment leads to alterations in dopamine function (PND21–60).	Hypermethylation of Nr3c1 is in response to dual deltamethrin and corticosterone exposures during development.	[55]
Corticosterone	C57BL/6 N mice	Drinking water	25 μg/mL	From adolescence through adulthood

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ISSN: 1880-7062

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