Developmental Neurotoxicity of Pesticides

  • Pesticeides are divided into 2 categories: Inorganic and Organic Compounds

    • Classified based on

      • chemical structure

      • environmental stability and toxxicity

      • pathway in which they penetrate and affect target organisms

Flow of Pesticides in Nature

Sources of exposure:

  • Residential factors

  • Exposure for the food supply

  • Agricultural related exposures

  • Exposures from water

Types of Pesticides:

  • Insecticides

  • Fungicides

  • Nematicides

  • Rodenticides

  • Acaricides/Miticides

  • Molluscicides

  • Bactericides

  • Algicides

  • Avicides

  • Herbicides

Major Pesticides and their toxicities

  • Organophosphates → Most are highly toxic

  • Organochlorines → HIgh Toxicity

  • Pyrethrins and Pyrethroids → Low to moderate

  • N-methyl carbamates → moderate to highly toxic

  • Neonicotinoids → lowe than Ops and carbamates

Effects of Organophosphates

  • highly toxic

  • half-life is shorter than organochlorine pesticides (DTT)

  • affect attention, mental and conceptual flexibility

How do Organophosphates affect the brain?

Apoptosis:

As Developmental Neurotoxicant

Examples of Ops:

Acetyl Cholinesterase(AChE) inhibitors → building AChE levels in the synaptoc cleft → overstimulation of ACh muscarinic and nicotinic receptors → causing organophosphate poisoning

  • This occurs in the brain, neuromuscular junction and autonomic ganglia

  • typically AChE breaks ACh into choline and taken back into the axon terminal

  • increased ROS

  • Activates BAX (pro-apop)

  • Activates Bcl-2 and Bcl-X (anti-apop)

  • Then activate cyt-c

  • memory loss, anxiety and neuropsychological development

  • Cross the placental and causes developmental neurotoxicity

  • Maternal exposure impairs motor and cognitive development in newborns and infants

  • may contribute to autism

  • locomotor deficits

  • Chloropyrifos (a type of Ops): exerts opposing effects on axonal and dendritic growth in primary neuronal cultures

    • affects cerebellar granule neurons at different stages of development

    • Causes apoptosis by excitotoxicity, oxidative stress, and irreversible inhibition of AChE

  • Malathion: targets cholinergic neurtransmitter systems

    • causes memory and cognitive disorders

    • shown neuronal degeneration in the cortex, and hippocampus

Effects of Organochlorine

Effect on Neurotransmitters

  • alters expression of protein associated with neurotransmission in the frontal cortex

  • GABA

    • GAT1 → Removes GABA from cleft

    • vGAT → Loads GABA in vesicles

    • GABAa → inhibitory neurotransmitter

  • Glutamine

    • vGlut → Loads Glut in vesicles

    • GluN2B → NMDA receptor subtype

  • Dopaminergic

    • DAT → reuptake protein

    • Dopamine D2 Receptor → Postsynaptic receptor

Endosulfan: neurodevelopmental disruptor resposible for neurobehavioral deficits. Affects frontal cortex proteins