Neurotoxic Effects of Pyrethroid Insecticides: Parkinson’s, Alzheimier’s, Lou Gehrig’s Disease(ALS), ADHD, Autism, etc. Review: B. Windham (Ed.)

Pyrethroids are a class of synthetic insecticides involved in different neurological disorders affecting humans- especially infants/fetus, the elderly, and those with chronic neurological or immune conditions (1,2,3,4,5). Studies have documented that chronic exposures can cause chronic health conditions or symptoms similar to such conditions as Parkinson’s(1), Lou Gehrig’s Disease(ALS)(2), Alzheimer’s Disease(3), ADHD/autism(4), and developmental deficits/birth defects/learning disabilities(4,5).

Pyrethroids cross the blood-brain barrier and exert their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson's disease and other neurological conditions through several pathways. Studies suggest that neonatal exposition to permethrin or cypermethrin induces long-lasting effects after developmental exposure giving changes in open-field behaviors, striatal monoamine level, and increased oxidative stress. (1b) Low doses of permethrin can reduce the amount of dopamine transporter immunoreactive protein in the caudate-putamen of the dorsal striatum of the brain(1a). The study also suggests that previously reported reductions in dopamine uptake of striatal synaptosomes of high-dose mice may be due to nondegenerative tissue damage within this region as opposed to reductions of dopamine transporter protein or death of nigrostriatal terminals.  Another study found an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 hours of exposure to pyrethrin pesticides(1c).  These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD.    Treatment with deltamethrin caused nerve cell loss and the appearance of signs of neuronal sufferance primarily in layer III of frontal cortex as well as in the dentate gyrus and to a lesser extent in the CA1 and CA3 subfields of hippocampus(1d). Deltamethrin induced also astrogliosis. Dopamine and the dopamine plasma membrane transporter decreased significantly in hippocampus and striatum. These findings indicate that dermal exposure to the pyrethroid insecticide deltamethrin using an administration module mimicking a possible long-lasting occupational skin contact is accompanied by cerebrocortical injury and loss of hippocampal and striatal dopamine and dopamine transporter. The sensitivity of dopaminergic system in our experimental model suggests that dermal exposure to deltamethrin could represent a risk factor for Parkinson's disease. Collectively These studies provide further evidence that insecticides can affect the primary neurodegenerative substrate of Parkinson's disease.

Chronic exposure to pyrethroid pesticides has been found to cause Lou Gehrig’s Disease (ALS) or symptoms similar to ALS(2), and Alzheimer’s Disease(3). Chronic exposure to Pyrethroid insecticides has also been found to cause ADHD, developmental deficits, reproductive problems, and to have a significant correlation to Autism(4).

Ref:

1(a)Immunohistochemical changes in the mouse striatum induced by the pyrethroid insecticide permethrin. Pittman JT, Dodd CA, Klein BG.  Int J Toxicol. 2003 Sep-Oct;22(5):359-70; & (b)Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids. Nasuti C, Gabbianelli R, Falcioni ML, Di Stefano A, Sozio P, Cantalamessa F. Toxicology. 2007 Jan 18;229(3):194-205; & (c)Pyrethroid pesticide-induced alterations in dopamine transporter function. Elwan MA, Richardson JR, Guillot TS, Caudle WM, Miller GW. Toxicol Appl Pharmacol. 2006 Mar 15;211(3):188-97; & (d) Influence of dermal exposure to the pyrethroid insecticide deltamethrin on rat brain microanatomy and cholinergic/dopaminergic neurochemistry.  Tayebati SK, Di Tullio MA, Ricci A, Amenta F. Brain Res. 2009 Dec 8;1301:180-8;

2. Vaccari A, Ruiu S, Mocci I, Saba P,Bernard B. Brodie. Selected pyrethroid insecticides stimulate glutamate uptake in brain synaptic vesicles. Neuroreport 1998 Oct 26;9(15):3519‑23; Gassner B, Wuthrich A, Scholtysik G, Solioz M; The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther 1997 May;281(2):855‑60; Narahashi T. Nerve membrane Na+ channels as targets of insecticides. Trends Pharmacol Sci 1992 Jun;13(6):236‑41; Zhao X, Dai S, Chen G. Inhibition of glutamate uptake in rat brain synaptosome by pyrethroids. Chung Hua Yu Fang I Hsueh Tsa Chih 1995 Mar;29(2):89‑91; Eldefrawi AT, Eldefrawi ME. Receptors for gamma‑aminobutyric acid and voltage‑dependent chloride channels as targets for drugs and toxicants. FASEB J 1987 Oct;1(4):262‑71; D. Zuccari Bissacot and I. Vassilieff. HPLC Determination of Flumethrin, Deltamethrin, Cypermethrin, and Cyhalothrin Residues in the Milk and Blood or Lactating Dairy Cows. Journal of Analytical Toxicology, Volume 21, Number 5, September 1997, pp. 397 –402.; Gassner B, Wuthrich A, Lis J, Scholtysik G, Solioz M. Topical application of synthetic pyrethroids to cattle as a source of persistent environmental contamination.J Environ Sci Health B 1997 Sep;32(5):729‑39; Patient Information Network,Exposure Survey of patients with ALS, http://members.aol.com/alspinpoint/results.html; & McGuire, Longstreth et al, Occupational exposures and amyotrophic lateral sclerosis; Am J Epidemiol 1997 Jun 15; 145(12):1076-88 & Baker, 1996; & Motor neuron disorder simulating ALS induced by chronic inhalation of pyrethroid insecticides;Doi H, Kikuchi H, Kira J et al; Neurology. 2006 Nov 28;67(10):1894-5; & [A new method for early detection of neurotoxic diseases (exemplified by pyrethroid poisoning)], Müller-Mohnssen H, Hahn K, Gesundheitswesen. 1995 Apr;57(4):214-22. German. Toxicology. 2007 Jan 18;229(3):194-205. Epub 2006 Oct 29; Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids; Nasuti C, Cantalamessa F et al; Toxicology. 2007 Jan 18;229(3):194-205. Epub 2006 Oct 29; & Effect of pyrethroid-based liquid mosquito repellent inhalation on the blood-brain barrier function and oxidative damage in selected organs of developing rats; Gupta A, Nigam D, Gupta A, Shukla GS, Agarwal AK; J Appl Toxicol. 1999 Jan-Feb;19(1):67-72;

3. (a) Repeated Exposure to Pesticides Increases Alzheimer's Disease Risk, K. M. Hayden , Neurology. 2010;74:1524-1530; & (b) The effects of environmental neurotoxicants on the dopaminergic system: A possible role in drug addiction. Jones DC, Miller GW. Biochem Pharmacol. 2008 Sep 1;76(5):569-81; & The toxic connection to Alzheimer’s Disease, Review, B. Windham (Ed.), www.flcv.com/alzhg.html

4. Pyrethroid Insecticides and Developmental Conditions(ADHD, birth defects, learning disabilities): Review – B. Windham (Ed.) www.flcv.com/PestADHD.html

5. Health Effects of Pyrethroid Insecticies: B Windham (Ed.) www.flcv.com/PyrethrR.html & Health Effects of Pesticides: B. Windham (Ed.) www.flcv.com/pesticid.html