Glutamate, T cells and multiple sclerosis | JoVE Visualize

Area of Science:

Neuroimmunology
Neuropharmacology
Cellular Neuroscience

Background:

Glutamate is a key neurotransmitter with essential functions, but its excess causes excitotoxicity and brain damage in various pathologies.
Glutamate receptors (GluRs) mediate both beneficial and detrimental glutamate effects, and are expressed in neural and non-neural cells, including T cells.
Multiple Sclerosis (MS) involves autoimmune T cells, and abnormal glutamate levels and signaling are implicated in its pathogenesis.

Purpose of the Study:

To review the multifaceted role of glutamate and its receptors in the nervous system and T cell function.
To explore the contribution of glutamate signaling abnormalities to Multiple Sclerosis (MS) and its animal model (EAE).
To discuss potential therapeutic strategies targeting glutamate pathways for MS treatment.

Main Methods:

Review of existing literature on glutamate, glutamate receptors, T cell function, and Multiple Sclerosis.
Analysis of studies investigating glutamate levels, receptor expression, and signaling in MS patients and EAE models.
Examination of the effects of existing MS therapeutics and experimental approaches on glutamate excitotoxicity and T cell activation.

Main Results:

T cells express functional glutamate receptors and can be activated by glutamate, influencing functions like migration and cytokine secretion.
In MS and EAE, elevated glutamate levels, altered GluR expression (e.g., AMPA GluR3 on T cells), and abnormal responses to glutamate are observed.
Certain MS drugs (Fingolimod, dimethyl fumarate, glatiramer acetate) demonstrate neuroprotective effects against glutamatergic damage.
Modulation of mGluR4 shows protective effects in EAE, suggesting its therapeutic potential.

Conclusions:

Abnormal glutamate levels, T cell activation by glutamate, and glutamate release by T cells are significant contributors to MS pathogenesis.
Targeting glutamate receptors with antagonists or enhancing protective pathways like mGluR4 presents viable therapeutic avenues for MS.
Novel strategies like 'brain to blood glutamate scavenging' warrant investigation for their potential to reduce neurotoxicity and T cell activation in MS.