Neurotoxicology Flashcards
what part of the body is CNS
brain, spinal cord
what part of the body is PNS
nerves, ganglia
what part of the body is ENS
digestive tract
what does brain step and midbrain control
blood pressure and respiration, visual and auditory systems
what does cerebellum do
posture and coordination of movement
what does diencephalon do
Thalamus: relays infomation to and from cortex
Hypothalamus: hormone secretion and autonomic nervous system
what does the cerebral hemispheres do
Cerebral cortex: perception, cognition, memory
Hippocampus: learning and memory
Basal Ganglia: assists cortex with motor function
what is BBB made of
endothelial cells and astrocytes
what chemicals is the nervous system vulnerable to
lipophilic chemicals
why is neuron loss permaneny
neurons do not divide
what is neuronopathy
damage to the cell body
examples of chemicals that lead to neuronopathy
methylmercury, MPTP
what is axonopathy
damage to neuronal axons and dendrites
what is proximal axonopathy
alterations in cell body and adjacent axon
what is distal axonopathy
alteration in terminal axon
examples of chemicals that lead to axonopathy
acrylamide
what is myelinopathy
damage to myelin sheaths
what is affected in central myelinopathies
oligodendrocytes in CNS
what is affected in distal myelinopathies
Schwann cells in PSN
what is indirect neurotoxicity
toxins in blood or damage to CNS vessel
example of chemical that leads to indirect neurotoxicity
carbon monoxide
example of chemical that leads to myelinopathy
lead
what is synaptic and neuromuscular toxicity
alterations in neurochemistry
examples of chemicals that lead to synaptic and neuromuscular toxicity
tetrodotoxin, botulinum toxin, organophosphates, bungarotoxin
describe methylmurcury neuronopathy
- environmental exposure
- bioaccumulates
- lipophilic (enters CNS easily)
- brain regions/neurons affected
methyl mercury toxicity is not correlated with?
cellular accumulation
how does methyl mercury bind
covalently binds -SH groups
what are the changes observed with methylmercyry toxicty
- glycolysis
- neurotransmitter release/reuptake
- mitochondrial respiration
- oxidative stress
- protein and nucleic acid synthesis
what does increased oxidative stress lead tp
- impaired GSH antioxidant system
- generation of reactive oxygen species
altered membrane potential involves what molecules
Na/K
ATPase contains how many SH groups
2
what is the role of Na/K/ATPase
- maintains neuronal cell potential
what is Na/K/ATPase inhibited by
MeHg (methylmurcury
What does methyl mercury do regarding cell potential
leads to increased NA concentration in the cell
which leads to increase n calcium and subsequent neurotransmitter release
what is the selective neuronopathy of methyl mercury neurotoxicity in adults
cerebellum and visual cortex affected
- cerebellar granule cells particularly vulnerable but with increased exposure other neurone also die
describe how the cortex if affected with methyl mercury neuronopathy in adults
peripheral vision disturbance and blindness
describe how the cerebellum is affected with methyl mercury neuronopathy in adults
ataxia, general incoordination, loss of sensation
describe how basal ganglia are affected with methyl mercury neuronopathy in adults
tremors, chorea, intellecutual impairment
describe how a fetus in utero is affected by methyl mercury neurotoxicity
- delayed growth/development
- impaired movement
- intellectual disability
- cerebral palsy
what is MPTP
a contaminant of synthetic heroin
how is MPTP transported
transported into neurons via dopamine transporter
where does MPTP metabolize
in astrocytes
effects of an acute high dose fo MPTP
loss of single population of neurons= imbalance of pathway
= paralysis, akinesia
effect of lower dose of MPTP
delayed development of parkinsonism
what is the primary site of toxicity of axonopathies
the axon
what is the role of an axon
communicate with neurons and tissues; electrical impulses, transport of molecules to and from cell body
explain how fast transport of axons goes
bi-directional movement of membrane associated materials
explain slow axonal transport
primarily anterograde transport of cytoskeletal proteins
what is 2,5-hexanedione
neurotoxic metabolite of n-butyl-ketone and n-hexane
what are the symptoms of 2,5-hexanedione toxicity
swelling and neurofilament accumulation in distal axon
accumulation of neurofilaments in distal axon is a symptom of what
2,5-hexanedione toxicity
how does 2,5-hexanedione cause neurofilament accumulation in distal axon
there is no change in neurofilament synthesis but transport is accelerated which leads to accumulation within the distal axon
what is acrylamide
polymer used industrially and in laboratories
what is the main symptom of acrylamide toxicity
distal axon degeneration
- with prolonged exposure, dying back of axon occurs
explain the mechanism of action of acrylamide toxicity
- binds SH group on tubulin= microtubule disassembly
- minor swelling and neurofilament accumulation in distal axon
can a single dose of acrylamide affect you
can affect retrograde axonal transport without producing structural changes
what does acrylamide inhibit
- kinesin
- fast transport proteins
what is the main symptom of lead toxicity in adults
myelinopathy
- peripheral motor axons predominantly affected
how does lead toxicity
mimics ca2+ and interferes with Schwann cell Ca2+ transport
- accumulates in and damages mitochondria, depletes GSH (glutathione)
what happens initially with lead toxicity in adults
segmental demyelination
what happens eventually with lead toxicity in adults
wallerian axonal degredation
what are the symptoms of lead toxicity in children
cognitive decline
- impaired learning and memory
- tremors, ataxia, blindness, seizures
what if children are acutely exposed to a massive dose of lead
cerebral edema due to damage of microvascular endothelial cells
how does tetrodotoxin work
reversibly binds Na+ channel and prevents conduction of nerve impulse
what are the initial symptoms of tetrodotoxin
tingling around mouth, dizziness
what are the later symptoms of tetrodotoxin
ataxia, convulsions, respiratory paralysis, death
where does the botulinum toxin come from
bacteria
how does botulinum toxin work
irreversibly binds to SNARE proteins in peripheral cholinergic synapses and then decreases ACh release
what are the symptoms of botulinum toxin
progressive limb paralysis, difficulty swallowing, respiratory paralysis and death
