Powerpoint 11 Flashcards
What are two areas of the body that Lead (Pb) can affect?
Kidneys and Brain
True or False:
In prenatal exposure, lead can cross the placenta
True
what is the BBB formed by?
Brain endothelial cells lining the cerebral microvascularture
Which type of glial cells surround the BBB?
Endothelial cells and Astrocytes
Lead ________ the permeability of the BBB
Increases
Do the Cellular Effects or Neurological Effects deal with the brain?
Neurological effects
The BBB is a restrictive barrier that contains _______-______ capillaries with tight junctions
Non-fenestrated
Where are the tight junctions located? What significance does this have?
They are located between endothelial cells. They limit what passes between cells
What regulates Tight Junctions?
Protein Kinase C (PKC)
Pb exposure -> (activates/inhibits) PKC activation -> expression of _____ _____ proteins -> “leaky junctions” -> water diffuses into brain tissue from the capillaries -> ______
Inhibits; tight junction; edema
What supports the integrity of BBB and neurons in the brain?
Astrocytes
Does Pb targeting Astrocytes directly or indirectly disrupt the BBB and neurons?
Indirectly
True or False:
Neurons are more sensitive to lead than Astrocytes
True
True or False:
Despite being less sensitive to Lead, there are higher concentrations of Lead in Astrocytes than neurons
True!
Astrocytes function as mini versions of which organs to regulate the composition of interstitial fluid that surrounds the neurons in the brain?
Kidneys and livers
In what two ways do Astrocytes support the BBB biology?
Mechanically and biochemically
True or False:
the BBB is not affected by what happens to the Astrocytes
FALSE; if Astrocytes are compromised, so is the BBB
_____ causes the BBB dysfunction and neuronal injury by activating the glial cells (microglia and astroglia)
lead (Pb)
What three things can Lead act on at the same time?
- microglia
- Astrocytes
- neuron
What is important for tight junction stability?
Low levels of Occludin
Microglia and Astrocytic activation -> inflammatory cytokines and response -> ROS and oxidative stress -> ____ and _____ injury
BBB; neuronal
What are the three groups of Caspases?
- initiator casapases
- effector caspases
- caspase activator and inhibitor
Which caspase group does this describe?
- Initiates the signal
- triggers other factors which goes and triggers effector caspases that signals apoptosis
Initiator Caspases
What are the mammalian proteins associated with Initiator Caspases?
Caspase 8, 9, and 10
What mammalian proteins are associated with Effector Caspases?
Caspase 1, 2, 3, 4, 5, 6, 7, 11, 12, and 13
What mammalian proteins are associated with Caspase activator and inhibitor?
Apaf-1, FADD, c-FLIP
What is the role of Caspase activator and inhibitor?
Mediator
________ are a family of cysteine proteases that are involved in apoptosis
Caspases
Caspases require _________ processing for their activation
Proteolytic
Which is the most characterized effector caspases?
Caspase-3
Effector caspases cleave many important intracellular substrates including:
- Morphological changes in apoptosis such as chromatin condensation
- Nucleosomal DNA fragmentation
- Breakdown of nuclear envelope
- Formation of apoptotic bodies
Lead exposure resulted in increased levels of activated caspase 3 in which brain areas 24 hours after exposure?
- cerebrum (cortex)
- Thalamus
- Caudate/Putamen
