Reexam of Neuro toxicity module

Reexam of Neuro toxicity

  1. Unlikely to cause confusion / disorientation (2p) Select one alternative:

    • Stroke
    • Liver failure
    • Spider byte
    • Ethanol intoxication
  2. Relevant sources of occupational exposure to lead (2p) Select one or more alternatives:

    • Exhaust gases

    • Welding

    • Construction sites /old paint

    • Toy manufacturing

  3. Sort the following elements in the correct hierarchical order (3p)

    Endpoint: Circadian disruption
    Biomarker: Circadian entrainment
    Mechanism: interference with glucocorticoid receptor signaling

  4. Define excitotoxicity. (3p)

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    Excitotoxicity is a condition of central neuronal death due to an excess of glutamate or related excitatory molecules binding to their respective receptors.

    Describe two (2) circumstances which promote excitotoxicity.

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    Ischemia (Stroke):
    During a stroke, reduced blood flow leads to oxygen and glucose deprivation. This disrupts ATP production, impairing ion pumps in the synaptic cleft, triggering calcium overload and neuronal death.

    Traumatic Brain Injury (TBI):
    Physical injury to the brain can disrupt the regulation of glutamate release and clearance. Damaged neurons release excess glutamate, exacerbating excitotoxic damage in the surrounding tissue.
  5. Describe three (3) neurotoxic mechanisms which can account for the developmental neurotoxicity of methylmercury (MeHg). (3p)

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    1. Oxidative Stress: Methylmercury (MeHg) increases reactive oxygen species, damaging neural cells during critical developmental stages.

    2. Increased Intracellular Calcium: MeHg disrupts calcium homeostasis, impairing cell signaling and promoting cell death in developing neurons.

    3. Mitochondrial Dysfunction: MeHg interferes with mitochondrial function, reducing energy production essential for neural growth and repair during development.

  6. Neurotoxin Y blocks the Na^+^/K^+^ ATP-ase. (2p)

    What effect does neurotoxin Y have on resting membrane potential?

    What effect does neurotoxin Y have on action potential?

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    Effect on Resting Membrane Potential:  
    Neurotoxin Y blocking the Na⁺/K⁺ ATPase would reduce the resting membrane potential, making it less negative (depolarized). This occurs because the pump normally maintains the ionic gradient by moving 3 Na⁺ ions out and 2 K⁺ ions in, creating a net negative charge inside the cell. If the pump is inhibited, the ionic gradients deteriorate, reducing the difference between the inside and outside of the membrane.

    Effect on Action Potential:
    Initially, there may be no immediate effect on action potential generation, as it primarily depends on voltage-gated Na⁺ and K⁺ channels. However, over time:
    - The loss of ionic gradients would diminish the driving force for Na⁺ influx and K⁺ efflux.
    - This would impair action potential amplitude and frequency because the depolarization and repolarization phases would be less effective.

    Eventually, neurons may become unable to fire action potentials due to complete loss of ionic gradients.
  7. Why is the nervous system more sensitive to neurotoxicants during development as compared to the adult state? Describe three (3) specific features and motivate. (3p)

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    1. Window of susceptibility. Neuron cells are at window of susceptibility during development. Neurotoxicants can affect the timing of development and formation of neuron connections causing permanent malfunction, which is different in adult neuro system.

    2. Limited cell replacement. Though, synapto-genesis happens through the life, proliferation does not. Neuro cells are not readily to be replaced after damaging during development.

    3. Weaker defenses. During development, immature BBB and absence of key enzyme which help us detoxicification lead to our neuro system more vulnerable to neurotoxicants.

  8. Define the concept of “window of susceptibility”. (1p)

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    Windows of susceptibility refer to specific periods in an individual's life when they are more vulnerable to the effects of environmental health hazards.
  9. Neurotoxin X block K+ channels in an open state. (2p)

    What effect does neurotoxin X have on resting membrane potential?

    What effect does neurotoxin X have on action potential?

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    Effect on Resting Membrane Potential:  
    Neurotoxin X, by blocking open K⁺ channels, would cause the resting membrane potential to become less negative (depolarized). This happens because K⁺ efflux through leak channels is a key factor in maintaining the negative resting potential. Blocking these channels reduces K⁺ efflux, leading to a buildup of positive charge inside the cell.

    Effect on Action Potential:
    1. Depolarization Phase: The initial depolarization caused by Na⁺ influx during an action potential would remain largely unaffected, as it is governed by voltage-gated Na⁺ channels.
    2. Repolarization Phase: Blocking open K⁺ channels impairs the efflux of K⁺, which slows or prevents repolarization of the membrane. This would result in a prolonged action potential and delayed return to the resting membrane potential.


    Overall, the neuron's ability to reset for subsequent action potentials could be impaired, leading to altered signaling.