»Trött i hjärnan« osynligt handi- kapp som kan ge stora problem Störd glutamatreglering kan förklara bristande informationsfiltrering

Cognitive impairment with decreased concentration capacity and mental fatigue makes rehabilitation from a stroke, brain trauma, meningitis or neuroinflammation difficult, and often hampers going back to work. According to our hypothesis, down regulation of the glutamate transport protein GLT-1 in the hippocampus and cerebral cortex is one pathogenic factor underlying mental fatigue. Glutamate is one major signal substance for information intake and processing in the brain. The GLT-1 protein, localised to astrocytes and, upon activation, also microglial cells, is considered to play key roles in the regulation of extracellular glutamate. A slight disturbance of the astroglial regulation of extracellular glutamate could lead to local microglial activation with the production of proinflammatory cytokines, astrocyte swelling, and, due to such swelling, decreased extracellular space. During these conditions, there is a decrease in both the glutamate release and the neuronal transmission. It is proposed that this decreased transmission could be one correlate at the cellular level to the mental exhaustion that the person could experience. Pharmacological treatment, probably with glial cells as targets, could restore dysfunction in the glutamate transmission and make the person less susceptible to pathological mental fatigue.