Glutamate cortex

GLT1/EAAT2 (SLC1A2) Astrocytes in cerebral cortex, hippocampus 5-100 Clearance of interstitial glutamate... 

It is equally well known that if a neuron dies, or is destroyed, then any other neuron, which had been innervated by it, gradually becomes supersensitive to the NT it released. In the case of degenerating pyramidal cells this would be glutamate, the excitatory NT. Not surprisingly, undercutting the cortex in animals to produce a deafferentation of some of its neurons not only renders them more likely to show epileptic-like discharges but neurons in hippocampal slices from kindled rats and human focal cortex show supersensitivity to the excitatory amino acids. Such supersensitivity could make some neurons so easily activated that they become epileptic . 

While there are some reports of increased NMDA and non-NMDA receptor number in various cortical regions of schizophrenics including the prefrontal cortex, there are also indications of impaired glutamate innervation, such as reduction in its neuronal uptake sites (Ishimaru, Kurumaji and Torn 1994). Also it has been found that levels of the mRNA for the NRI subunit of the NMDA receptor in the hippocampus and its D-aspartate binding sites in the temporal cortex are both reduced more on the left than right side in schizophrenic brain. This is another indication of greater malfunction on the left side of the brain and the possibility that some schizophrenic symptoms arise from an imbalance between cross-cortical activity. 

Ishimaru, M, Kurumaji, A and Toru, M (1994) Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics evidence for glutamate hypothesis. Biol. Psychiat. 35 84-95. 

Low concentrations of solubilised jS-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of A/i below those generally neurotoxic. Since jS-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism), /i-amyloid can also reduce the secondary effects of Mi receptor activation such as GTPase activity... 

Galantamine is a ChE inhibitor, which elevates acetylcholine in the cerebral cortex by slowing the degradation of acetylcholine.37 It also modulates the nicotinic acetylcholine receptors to increase acetylcholine from surviving presynaptic nerve terminals. In addition, it may increase glutamate and serotonin levels. The clinical benefit of action of these additional neurotransmitters is unknown. 

Lena, I., Parrot, S., Deschaux, O. et al. (2005). Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep - wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J. Neurosci. Res. 81, 891-9. 

Manns, I. D., Mainville, L. 8r Jones, B. E. (2001). Evidence for glutamate, in addition to acetylcholine and GABA, neurotransmitter synthesis in basal forebrain neurons projecting to the entorhinal cortex. Neuroscience 107, 249-63. 

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