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Section C
How Is Lead Affecting Cognition, and What
Other Chemicals Should Concern Us?
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Success In Decreasing Severity
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Synapse Is the Fundamental Unit
! Synapses are gaps between neurons that mediate neuron-to-neuron communication
! Learning involves the development of neuronal pathways (a series of neurons
communicating with each other) through the strengthening of synapses
! Pre-synaptic neuron communicates with the post-synaptic neurons through the
release of neurotransmitters and co-neurotransmitters
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Learning Is Gain and Loss of Synapses
Many, many new synapses are made
during development
Lead exposure might
decrease pruning,
creating less efficient
neuronal pathways
Synapses are lost if strengthening does not occur through environmental
enrichment. This process of synapse loss (pruning) increases the efficiency of
the strengthened synapse and is equally important for learning.
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Diseases of the Synapse
! Bars indicate the period of emergence of symptoms and diagnosis. In normal
subjects, spine numbers increase before and after birth; spines are selectively
eliminated during childhood and adolescence to adult levels. In ASD, exaggerated
spine formation or incomplete pruning may occur in childhood, leading to increased
spine numbers. In schizophrenia, exaggerated spine pruning during late childhood or
adolescence may lead to the emergence of symptoms during these periods. In
Alzheimer's disease, spines are rapidly lost in late adulthood, suggesting perturbed
spine maintenance mechanisms that may underlie cognitive decline.
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Xenobiotics Chemicals
! Synapses are targets for many other xenobiotics chemicals (interfere with
neurotransmitter clearance from the synapse)
Monoamine oxidase breaks down catecholamines
! Targets cell surface proteins that re-uptake neurotransmitters or enzymes that
degrade neurotransmitters
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Targeting Synapse
! Enzymes that degrade neurotransmitters
- Organophosphate insecticdes—acetylcholinesterase
- Tricyclic antidepressants—MAO
! Reuptake inhibitors
- Serotonin—Zoloft, Lexapro, Celexa
- Dopamine—cocaine
! Receptor/co-receptor
- Phencyclidine (PCP)/glutamate receptor
- Tetrahydrocannabinol (THC)/cannabinoid receptors
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Toxicant Target Neurotransmitter Homeostasis
! Toxicant target neurotransmitter homeostasis: specific effects on
behavior
! Examples of neurotransmitters
- Catecholamines—
dopamine, norepinephrine
- Excitatory amino acids—
glutamate and aspartate
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Insecticides Inhibit AchE: Acute Cholinergic Toxicity
! Organophosphates (examples,
agriculture)
- Chlorpyrifos
- Disulfoton
- Fenthion
- Malathion
- Methyl parathion
- Mevinphos
- Trichlorfon
! ! Carbamates (also used
medically)
- Aldicarb
- Carbaryl
- Carbofuran
- Formetanate HCl
- Methiocarb
- Methomyl
- Oxamyl
- Pirimicarb
- Propoxur
- Thiodicarb
Millions of pounds of these neurotoxicants are used annually
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Acute Toxicity Organophosphate Insecticides
! SLUD or signs of excess excretion (salivation, lacrimation, urination,
defecation)
! Bradycardia
! Hypotension
! Muscle paralysis
! Respiratory depression
! Seizures and convulsions
! Host of others, including headaches, forgetfulness, sleep disorders
possible
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Other Toxicant Examples (Small List)
Acute
Chronic
Methyl mercury
Cognitive development and motor
skills
Organophosphate—paralysis
Cognitive, motor
Herbicides—asphyxiation (rotenone,
Paraquat)
Parkinson’s disease
Particulate matter
Autism
Persistent organic pollutants
(polychlorinated and
polybrominated)
Cognitive development
Solvents—encephalopathy
Mood disorder
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Lecture Evaluation
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