Inflammation
Acute inflammation (via secretion of inflammatory cytokines TNF and IL-1B) has this acute impact on synaptic glutamate transmission.
What is TNF and IL-1B initially stimulate increased glutamate neurotransmission?
This is the most common subtype of Astrocyte
What are Protoplasmic Astrocytes?
Oligodendrocytes synthesize this important substance
What is Myelin?
This is the primary function of Microglia in the CNS
What is the primary immune cell?
Studies have shown poisoning of glial Excitatory Amino Acid Transporters (EAAT) in the medial PFC (mPFC) generates these class of psychiatric symptoms
What are depressive symptoms?
Chronic inflammation (via binding pre-synaptic mGluR2/3 receptors and synaptic AMPA/NMDA receptors) has this impact on synaptic glutamate transmission
What is decreased synaptic transmission (via negative feedback loop from pre-synaptic mGluR2/3 receptors and down-regulation of synaptic AMPA/NMDA receptors)?
These are two functions of Astrocytes
Any of the following:
providing neurotrophic support (BDNF)
maintaining synaptic homeostasis
Regulating synaptic pruning
Participating in neuron–glia signaling
Coordinating neuro-metabolic coupling
Mitigating oxidative stress
Modulating glutamate metabolism
Maintaining integrity of the BBB
Impaired myelin synthesis may result from excessive binding of this glutamatergic receptor on Oligodendrocytes
What is excessive binding of the NMDA receptor?
Microglia differ from the other glial cells in that they develop embryologically from these cells
What is mesoderm yolk sac (versus other glia from ectodermal neural plate and crest)
This is one of the several cytokines found to be associated with depression and schizophrenia
What is/are any two:
Interleukins: IL-6 and IL-1B
TNF
Interferon: IFN-y
Extra-synaptic binding of NMDA receptors has this impact on neural plasticity
What is inhibiting growth factors such as BDNF and thereby impairing neural plasticity
These are the Glutamate transports on Astrocytes primarily responsible for reuptake of Glutamate from the synapse
What are Excitatory Amino Acid Transporters (EAAT 1-2)?
Oligodendrocytes are very sensitive to glutamatergic cell toxicity via oxidative stress and through binding of these two types of glutamatergic receptors
What are the AMPA and Kianate receptors?
These are two of the different morphological states of Microglia which impact effects on inflammation and glutamate
Surveillance state (scanning CNS)
Classic Activated state (pro-inflammatory)
Alternate Activated state (anti-inflammatory)
Acquired Deactivation (combo of above)
Primed/Chronic activation (hyper-inflammatory)
During inflammation, Tryptophan is shunted away from synthesizing this neurotransmitter, and instead shunted towards synthesizing this toxic substance with glutamate like properties
What is Serotonin and Kynurenin respectively?
This is at least one of the several mechanisms by which inflammation impacts Glial cell regulation of glutamate, leading to increasing extra-synaptic glutamate and excito-toxicity
What are any of the following:
1) What is reduced Astrocyte "buffering" via reduced availability of EAAT1/2 (from TNF, high levels of IFN-y, and other inflammatory cytokines) leading to spill over of glutamate?
2)What is Astrocyte activation of "inflammasome" via "DAMP/caspace1/IL-1B" pathway which reduces ability of astrocytes to clear glutamate
3) What is the way that inflammation "primes" and actives" Microglia (and Astrocytes, and Macrophages) to hyper-secrete large quantities of glutamate into the synapse which then spills over
This is the enzyme that re-encapsulates Glutamate in the pre-synaptic neuron
What are Vesicular Glutamate Transporters (VGLUT)?
Patients with mood disorders and schizophrenia have been found to demonstrate this in regard to oligodendrocyte function
What are: myelin loss and decreasing dendritic number and function
In addition to Glutamate, Microglia secrete these other three toxic substances into the synapse
What are Kynurenin, Quinolinic Acid, and reactive oxygen/nitrogen speceise?
These two glial cell types are essential for maintaining neural activity and neural circuit integrity via maintenance of both myelinated and unmyelinated regions of the axon
What are Oligodendrocytes (for myelinated regions) and Nodal Astrocytes (for unmyelinated Nodes of Ranvier)
Post-mortem studies of depressed suicide victims have revealed increased concentration of activated and primed microglia in this brain region known to be associated with depression
What is the Cingulate Gyrus (particularly the anterior cingulate and the subgenual cingulate gyrus)?
Within Astrocytes, this enzyme converts Glutamate into Glutamine which can be transported safely into the pre-synaptic neurons where it will be recycled back into Glutamate via this other enzyme
What are Glutamine synthase and Glutaminase respectively?
NG2+ cells (a special subtype of Oligodendrocyte precursor cell) directs the formation of these two types of synapses during brain development
What are glutamatergic and GABAnergic synapses?
Studies have found patients with neuropsychiatric disorders (including TBI and neurodegeneration) have increased prevalence of this state of microglial cell within the brain, which have this impact on inflammation
What is increase of "primed" microglia that have a heightened immune/inflammatory response to stimuli (and were less responsive to glutamate reuptake enhancing Riluzole compared with unprimed microglia from control subjects)
Post-mortem studies of depressed suicide victims have shown decreased astrocyte number and packing density in these brain regions (name 3):
Whare are: PFC, OFC, anterior and subgenual anterior cingulate, and amygdala