BLOCK 3: MPP: (3.5) GLUTAMATE

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Questions and Answers

What can excessive release or insufficient reuptake of glutamate lead to in pathological conditions?

Enhanced synaptic plasticity

Increased neurotransmitter synthesis

Excitotoxicity (correct)

Inhibition of neurotransmitter release

Which of the following is a consequence of excitotoxicity caused by glutamate?

Enhanced glutamate reuptake

Decreased intracellular sodium levels

Increased intracellular Ca2+ levels (correct)

Neuronal hyperpolarization

In which of the following diseases has excitotoxicity been implicated?

Asthma

Hypothyroidism

Hypertension

Alzheimer's disease (correct)

What effect does increased glutamate release have on neuroglia?

Enhanced microglial activation Signup and view all the answers

Which of the following statements about glutamate reuptake is true?

It prevents excessive excitatory signaling. Signup and view all the answers

What biological process is triggered by excessive glutamate signaling?

Apoptotic signaling pathways Signup and view all the answers

Which role does increased Ca2+ levels play in glutamate-induced neuronal damage?

Activates kinases leading to cellular damage Signup and view all the answers

What is the primary function of neuroglia in the nervous system?

Regulate neurotransmitter levels Signup and view all the answers

Which of the following conditions are neurodegenerative syndromes?

Huntington's disease and Alzheimer's disease Signup and view all the answers

How do neuroglia contribute to excitotoxicity prevention?

By controlling local ion concentrations Signup and view all the answers

What is one of the roles of neuroglia in neurotransmitter management?

They recycle neurotransmitters. Signup and view all the answers

Which of the following strategies is employed by neuroglia during neurotransmitter spillover?

Facilitate spatial buffering Signup and view all the answers

What is the primary consequence of excitotoxicity in the central nervous system?

Increased intracellular Ca2+ levels leading to neuronal death Signup and view all the answers

Which neuroglial function is crucial for maintaining neurotransmitter balance in the CNS?

Reuptake of glutamate from the synaptic cleft Signup and view all the answers

What role do NMDA receptors play in glutamatergic neurotransmission?

Require co-activation by glutamate and glycine to function Signup and view all the answers

How does increased glutamate release impact neuronal health during pathologic states?

Leads to a positive feedback cycle of cellular damage Signup and view all the answers

What is one of the main functions of metabotropic glutamate receptors?

Regulating gene expression in neurons Signup and view all the answers

Which process involves excessive activation of glutamate receptors leading to cell injury?

Excitotoxicity Signup and view all the answers

What condition can result from decreased reuptake of glutamate?

Increased apoptosis of neurons Signup and view all the answers

Which ions are predominantly allowed to flow through ionotropic glutamate receptors during activation?

Na+, K+, and Ca2+ Signup and view all the answers

What is a potential consequence of excitotoxicity linked to neurodegenerative diseases?

Increased neuronal death Signup and view all the answers

What is the primary function of glutamate in the central nervous system?

Mediating fast excitatory responses Signup and view all the answers

Which cellular mechanism could be targeted for pharmacological intervention in treating excitotoxicity?

Blocking glutamate receptors Signup and view all the answers

In what part of the brain are NMDA receptors predominantly expressed?

Hippocampus and cerebral cortex Signup and view all the answers

What is one major difference between ionotropic and metabotropic glutamate receptors?

Ionotropic receptors are ligand-gated ion channels Signup and view all the answers

How does neuroglia contribute to synaptic health?

By supporting neurotransmitter reuptake Signup and view all the answers

What therapeutic strategy could help in conditions associated with increased glutamate signaling?

Inhibiting excitatory receptor activity Signup and view all the answers

Study Notes

Glutamatergic Neurotransmission

Glutamate synapses are found across the central nervous system (CNS).
Glutamate binding to its receptors initiates neuronal excitation.
Glutamate pharmacology is a growing area of neuropharmacology.

Glutamate Receptors

Glutamate receptors can be separated into ionotropic and metabotropic receptors.
Ionotropic receptors are responsible for fast excitatory synaptic responses.
Ionotropic receptors allow the flow of sodium, potassium, and calcium ions across plasma membranes.

Ionotropic Glutamate Receptors

Three main subtypes of ionotropic receptors are classified by agonists: AMPA, kainate, and NMDA.
NMDA receptors are found in the hippocampus, cerebral cortex, and spinal cord.

NMDA Receptors

NMDA receptor activation requires simultaneous binding of glutamate and glycine.
NMDA receptors allow potassium efflux and sodium and calcium influx.
At rest, NMDA receptors are blocked by magnesium.
Depolarization of the membrane is needed to relieve the magnesium block and allow the receptor to become activated by glutamate and glycine.

Excitotoxicity

Increased glutamate release or decreased glutamate reuptake can lead to a cycle of increasing cellular damage.
Increased intracellular calcium levels can contribute to cell damage and further glutamate release.
Excitotoxicity is neuronal death caused by excessive cellular excitation from glutamate or other excitatory neurotransmitters.
Excitotoxicity is associated with neurodegenerative diseases including Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), stroke, and epilepsy.

Neuroglia

Neuroglia are non-neuronal cells that support neuronal function.
Neuroglia perform various functions, including myelin formation, local ion concentration control, neurotransmitter recycling, and providing nutrients to neurons.

Spatial Buffering (Neuroglia)

Neuroglia support the control of neurotransmitter spillover by removing extra neurotransmitters from the synapse.

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Description

This quiz explores the critical role of glutamatergic neurotransmission in the central nervous system. It covers various glutamate receptors, including ionotropic and metabotropic types, with a focus on the NMDA receptor's unique activation requirements. Test your knowledge of these fundamental neuropharmacological concepts.