Neurotransmitter brain lesions

Genetic and nutritional studies have illustrated the essential nature of copper for normal brain function. Deficiency of copper during the foetal or neonatal period will have adverse effects both on the formation and the maintenance of myelin (Kuo et al., 2001 Lee et al., 2001 Sun et al., 2007 Takeda and Tamana, 2010). In addition, various brain lesions will occur in many brain regions, including the cerebral cortex, olfactory bulb, and corpus striamm. Vascular changes have also been observed. It is also of paramount importance that excessive amounts of copper do not occur in cells, due to redox mediated reactions such that its level within cells must be carefully controlled by regulated transport mechanisms. Copper serves as an essential cofactor for a variety of proteins involved in neurotransmitter synthesis, e.g. dopamine P-hydroxylase, which transforms dopamine to nor-adrenahne, as well as in neuroprotection via the Cu/Zn superoxide dismutase present in the cytosol. Excess free copper is however deleterious for cell metabolism, and therefore intracellular copper concentration is maintained at very low levels, perhaps as low as 10 M. Brain copper homeostasis is still not well understood. 

Chang RSL, Tran VT, Snyder SH (1980) Neurotransmitter receptor localizations brain lesion induced alterations in benzodiazepine, GABA, 8-adrenergic and histamine H,-receptor binding. Brain Res., 190, 95-110. 

The effects of DBS on the cortex-basal-ganglia-thalamus-cortex motor loop appear to be more complex than initially believed. The paradox of DBS is that electrical stimulation of brain tissue (which presumably induces brain activation), has a similar effect as that of a surgical lesion of that same structure (which effectively destroys brain tissue). These two realities are hard to reconcile. As indicated by [64] the ultimate elucidation of this paradox depends on the nature of the complex and interactive neural connections in the brain that communicate through electrical and chemical processes. There is an emerging view that DBS has both excitatory and inhibitory effects on how brain circuits communicate with one another depending on the distance from the electrode, the cell structures activated and the direction of the activation (ortho- versus anti-dromic). The effect appears to modulate the activity of a network as well as neural firing patterns. Long term effects on neurotransmitters and receptor systems cannot be excluded [64]. 

Meister B, Ceccatelli S, Hokfelt T, Anden NE, Anden M, Theodorsson E (1989) Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus effects of monosodium glutamate (MSG) lesions. Exp Brain Res 76 343-368. 

Sauer, H., Wong, V. and BJorklund, A. (1995) Brain-derived neurotrophic factor and neurotrophin-4/5 modify neurotransmitter-related gene expression in the 6-hydroxydopamine-lesioned rat striatum. Neuroscience 65 927-933. 

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