Glutamate and fatigue

[Marco]

I've posted this in the non-ME/CFS related section but that doesn't rule out the possibility of relevance.

Firstly a mouse model that implicates the glutamate transporter GLT-1 in the mediation of exercise induced fatigue (interesting that extracellular glutamate is increased but lactate is decreased in relevant brain area in the fatigued rats) :

GLT‐1 mediates exercise‐induced fatigue through modulation of glutamate and lactate in rats

https://onlinelibrary.wiley.com/doi/full/10.1111/neup.12465

and a just recruiting study that aims to test the effectiveness of Riluzole (a drug which increases glutamate re-uptake) in treating fatigue in breast cancer patients :

Effects of Riluzole on CNS Glutamate and Fatigue in Breast Cancer Survivors With High Inflammation

https://clinicaltrials.gov/ct2/show/NCT02796755

Might be worth keeping an eye on?

 

[Marco]

Another interesting one :

Sleep Deprivation Distinctly Alters Glutamate Transporter 1 Apposition and Excitatory Transmission to Orexin and MCH Neurons

http://www.jneurosci.org/content/38/10/2505

Now I'm feeling a little sleep deprived myself so I can't quite work out whether GLT1 is solely involved in glutamate reuptake or in the transport of glutamate tramsmission across the synaptic cleft - or whether "Reduced GLT1 apposition was associated with tonic presynaptic inhibition of excitatory transmission to these neurons due to the activation of Group III metabotropic glutamate receptors" is a good thing

Anyway the takeaway message is that the glutamate transporter GLT1 plays a key role in modulating the activity or wakefullness promoting orexin or sleep promoting melanin-concentrating hormone neurons in the rat hypothalamus and that this modulating activity depends on whether or not the organism is sleep derpived. Presumably sleep deprivation uprates the excitatory role of GLT1 on sleep inducing MCH neurons?

ETA

They probably explained it better than I did (my text breaks added) :

SIGNIFICANCE STATEMENT Sleep–wake cycles are regulated by the alternate activation of sleep- and wake-promoting neurons. Whether and how astrocytes can regulate this reciprocal neuronal activity are unclear.

Here we report that, within the lateral hypothalamus, where functionally opposite wake-promoting orexin neurons and sleep-promoting melanin-concentrating hormone neurons codistribute, the glutamate transporter GLT1, mainly present on astrocytes, distinctly modulates excitatory transmission in a cell-type-specific manner and according to sleep history.

Specifically, GLT1 is reduced around the somata of orexin neurons while increased around melanin-concentrating hormone neurons following sleep deprivation, resulting in different forms of synaptic plasticity.

Thus, astrocytes can fine-tune the excitability of functionally discrete neurons via glutamate transport, which may represent novel regulatory mechanisms for sleep.