Cognition problems associated with changes in nerve signalling molecules

Muhlert N, Atzori M, De Vita E, Thomas DL, Samson RS, Wheeler-Kingshott CA, Geurts JJ, Miller DH, Thompson AJ, Ciccarelli O. Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions. J Neurol Neurosurg Psychiatry. 2014 Jan 15

OBJECTIVE: Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance.

METHODS: Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent 1H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. 

RESULTS:Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls.
CONCLUSIONS:The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS.

The balance of Glutamate (major excitatory nerve signalling molecule) and GABA  (major inhibitory nerve signalling molecule) is important to signs and symptoms because they effect signalling in the nerve circuits. However the interactions between them are complete because it is not simple that  excitation is a postive things because the excitation could stimulate or dis inhibit related excitatory or inhibitory circuits. This study tells us there are cognitive problems in MS and differences in glutamate levels but does not necessarily give easy solutions. Interfering with these essential transmitters is invariably associated with side-effects because they can’t target just one circuit in one part of the brain. e.g. the effect of baclofen (GABA stimulator) can give cog fog and floppiness, AMPA/NMDA (Glutamate inhibitors) can be likewise have very unpleasant side effects .

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