L20 & 21 Neurotoxicity Flashcards
Exposure to a teratogen in the pre-embryonic phase probably has an ‘all or nothing’ effect – what does this mean?
Damage to all or most cells causes death of the blastocyst - hence either you die or you live. Injury to only a few undifferentiated cells probably allows compensation and normal development.
Medications taken during the _ - _ weeks phase have the greatest potential to cause gross malformations by affecting _________ e.g. Thalidomide – inhibits _____ factors involved in limb differentiation. The type of malformation depends on which organs are most susceptible at the time of exposure.
3-8, organogenesis, homeobox
Folate deficiency is associated with _____ _____ defects (closure). What type of medications are folate antagonists?
Neural tube, anti-seizure meds - methotrexate, valproic acid, 5-florouracil, sulfasalazine, oral contraceptives, diphenylhydantoin, trimethoprim, and pyrimethamine.
Folates function as carbon donors in the synthesis of a.cid to a.acid? Directly in the synthesis of ___- and ____ bases? Indirectly in the synthesis of? ______ donor in remethylation of homocysteine to methionine?
Glycine to serine, purines and pyrimidine bases, transfer RNA, methyl donor
Tobacco Smoke - pre-natal and early postnatal exposure possibly the leading cause of environmentally induced developmental disease and morbidity. Increased risk of SIDS, increased learning, behavioral & attention disorders. Nicotine - a known neuroteratogen.
Tobacco Smoke - pre-natal and early postnatal exposure possibly the leading cause of environmentally induced developmental disease and morbidity. Increased risk of SIDS, increased learning, behavioral & attention disorders. Nicotine - a known neuroteratogen.
In utero exposure to ethanol causes fetal alcohol syndrome (FAS) – what is FAS?
Resulting in craniofacial dysmorphism, intrauterine & postnatal growth retardation, retarded psychomotor & intellectual development etc.
The only way drugs and toxins can get into the brian is via?
Blood vessels
Most drugs that have toxic effects on CNS function gain access by?
either being transported in OR lipid soluble
(+ able to avoid pgp-mediated efflux)
*P-glycoprotein pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity
Byproduct of manufacturing ATP from mitochondria?
ROS (reactive O2 species) can react with Fe3+ transition metal to create toxic byproducts
T/F - Adult CNS neurons have no neuronal stem cells
F- have a few
What hypothesis is suggested about people that get Parkinson’s?
ROS hypothesis = Production of DA generates Fe3+ which reacts with ROS to switch on pathway that activates apoptosis
Dynein and kinesin are? Which moves towards - end?
Cytoskeletal motor proteins involved in axonal transport on microtubles
Dynein moves towards - end (cell body) - retrograde
Kinesin moves towards + end (nerve terminal) - anterograde
What neurotoxins affect axonal transport?
Mercury -Binds to Beta subunit of tubulin (on the GTP binding site and since GTP provides energy for tubulin proteins to link, without it - disrupts MT formation, transport and disrupts neurite growth cones so that you no longer have tubulin and see the actin instead (actin is what the tubulin is wrapped around)
Taxol - MT stabilized in polymerized state, blocks transport (requires switching between polymerized & depolymerized states)
Colchicine, Vincristine -MT polymerization inhibitor, prevents MT formation and blocks transport
Imino-dipropionitrile - Blocks neurofilament, slows anterograde transport down the axon
All metals are potentially toxic yet essential for life - how?
Metals frequently bound to proteins for transport, storage and to limit their redox reactivity
Lead toxicity
a) Symptoms
b) Pathology
c) Recovery is accompanied by
d) Affects ____ and ___ transmission
a) Symptoms - lethargy, vomiting, irritability, “foot drop” or “wrist drop” due to demyelination and axonal degen with Schwann cell degen
b) Pathology - edema of brain due to extravasation of fluid from capillaries, loss of neuronal cells and gliosis
c) Recovery - accompanied by epilepsy, mental retardation optic neuropathy and blindness
d) Glutamergic and dopaminergic
