Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer’s disease

Table 6 Effect of pesticides on cognitive processes

Type of study	Sample	Type of pesticide	Exposure data	Cognitive implications	Ref.
Clinical/epidemiological studies. Cross-sectional	90 subjects with PD and 90 healthy subjects	OCs: δ-HCH	Concentration: NA. Exposure time NA	MMSE1 values in subjects with PD and without exposure to OCs: 27.66 ± 4.63. MMSE1 values in healthy subjects with exposure to OCs: 24.33 ± 4.31	[45]
Clinical/epidemiological studies. Cohort	13 postmortem brains of subjects without exposure and 4 postmortem brains of subjects with exposure	OCs	Concentration: NA. Exposure time: from 0 to 10 yr	Last CASI1 score of subjects without exposure: 67.9 ± 24.4. Last CASI1 score of subjects with exposure: 41.6 ± 22.8	[44]
Experimental studies	Strains of Caenorhabditis elegans (N2 BR5271)	OCs: DDT	Concentration: 3 μM. Exposure time of 2 h	No significant differences reported in Associative Learning Paradigm tests	[46]
Experimental studies	Wistar rats	OCs: Chlordane	Range of concentration: 1 to 100 nM. Chronic exposure	Exposure did not affect results of tests that measured spatial memory	[49]
Review studies	Multiple studies	OCs: TCDD	Range of concentration: 5 to 23 ppt. Single dose	Decreased performance in verbal and nonverbal memory tests	[48]
Clinical/epidemiological studies. Cases and controls, unpaired	33 subjects exposed to OPs and 33 subjects without exposure	OPs	Concentration: NA. Exposure time 2 yr	87% of exposed subjects had cognitive impairment. Exposure to OPs for 10 yr increased the risk of cognitive decline 17 times	[53]
Experimental studies	Wistar rats	OPs: Chlorpyrifos- oxon	Range of concentration: 1 to 100 nM. Chronic exposure	Rats exposed to OPs showed deterioration of spatial memory	[49]
Experimental studies	NMRI mouse	OPs: Chlorpyrifos	Concentration: 0.1, 1.0, 5.0 mg/kg. Single dose	Decreased locomotion response and novelty were observed in rats exposed to this OPs	[54]
Experimental studies	Transgenic AD model rats	OPs: Chlorpyrifos	Concentrations: 3 and 10 mg/kg. Exposure time of 21 d	Exposure was associated with accelerated cognitive impairment in male rats, as indicated in memory and recognition tests	[50]
Experimental studies	Wistar rats	OPs: Malathion	Concentration: 100 mg/kg. Exposure time of 14 d	Decrease in spatial memory (evaluated using Morris water maze). This decrease was related to tau hyperphosphorylation	[33]
Experimental studies	Cell culture hiPSC and Wistar rats	OPs: DFP	Cell culture concentration: 200 nM. Exposure time for 2 d. Murine concentration: 1.5 mg/kg. Exposure time for 7 d	Slight decreases in learning and memory tests in the Morris water maze tests, and in 0 new object recognition	[56]
Review studies	Multiple studies	OPs	Different conditions	Lower perfomance in MMSE was associated with the exposure, with a modestly increased risk of MCD	[58]
Review studies	Multiple studies	OPs	NA	Exposure produced psychotic episodes, and alterations in attention, memory, problem solving, abstraction and cognitive flexibility	[59]
Review studies	Multiple studies	OPs ester	Different conditions	Decreased attention, visual memory, persistent and longer cognitive dysfunction and short-term memory	[60]
Experimental studies	Sprague-Dawly rats	Cs: Carbofuran	Concentration: 1 mg/kg. Exposure time of 28 d	Rats exposed to this pesticide took longer time to solve the Morris water maze, relative to the control group	[32]
Experimental studies	NMRI mouse	Cs: Carbaryl	Concentrations: 0.5, 5.0, 20.0 mg/kg. Single dose	Decreased locomotion response and response to novelty test in rats exposed to this pesticide	[54]
Experimental studies	Sprague-Dawly rats	Cs: Carbofuran	Concentration: NA. Exposure time for 28 d	Exposed rats had longer escape latency time in the Morris water maze test. Exposure was related to spatial memory deficit	[63]
Experimental studies	Sprague-Dawly rats	Ps: Deltamethrin	Concentration: 12.5 mg/kg. Exposure time for 28 d	Rats exposed to this pesticide took longer time to solve the Morris water maze, relative to the control group	[32]
Experimental studies	Wistar rats	Ps: Cypermethrin	Concentration: 10 mg/kg and 25 mg/kg. Exposure time for 2, 3 and 6 wk	Cognitive impairment was induced; deficiencies in learning and memory of exposed rats occurred. These changes may be related to changes in calcium-dependent kinases and calmodulin	[69]
Experimental studies	Wistar rats	Ps: Cyfluthrin. Imiprothrin and Prallethrin	Concentrations: 25%, 50% and 75%. Exposure time of 45 d	Rats with the highest P exposure had higher cognitive impairment, when compared to control rats and other concentrations, possibly via increased activation of astrocytes in hippocampus	[34]
Clinical/epidemiological studies. Retrospective study of suicidal patients	Accidental intake of different Ns	Ns: Imidacloprid	Different concentrations. Single dose	Disorientation, altered mental status, lack of coordination and confusion	[79]

¹mean ± SD.

OCs: Organochlorines; OPs: Organophosphates; NA: Not available; DFP: Diisopropyl fluorophosphate; MMSE: Mini Mental State Examination; CASI: Cognitive Abilities Screening Instrument; Ps: Pyrethroids; Ns: Neonicotinoids; Cs: Carbamates; MCD: Major cognitive disorders; hiPSC: Human-induced pluripotent stem cells; δ-HCH: δ-hexachlorocyclohexane; DDT: Dichlorodiphenyltrichloroethan; AD: Alzheimer’s disease; TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin; PD: Parkinson disease.