Substrates neurological

But while we know in general which parts of the brain are involved in mood, we know very little about how the parts are involved and next to nothing about the details of how the neurological substrates are involved in various moods. And although we know more than we did 50 years ago, we still don t know how mood originates and how it s translated from neural activity to conscious awareness. Nevertheless, we can expect that the parts of the brain involved in mood play some role in mood disorders. 

Rosin, D. L., Hettinger, B. D., Lee, A. and Linden, J. Anatomy of adenosine a2a receptors in brain Morphological substrates for integration of striatal function [Comment]. Neurology 61 SI2-18,2003. 

Figure 3. The many ways to lose a HAT. Decreased amounts of functional CBP protein and subsequent CBP s loss of function has been observed in different contexts of neurological disorders and neuronal apoptosis. RTS (Rubinstein-Taybi Syndrome) results from a mutation on one cbp gene allele. In several cases of polyQ diseases, CBP can be sequestred by the mutated polyQ proteins, forming aggregates in the cytoplasm or the nucleus. CBP proteasomal degradation was also shown to be favored by polyQ proteins. CBP is a caspase-6 substrate in cerebellar granule neurons (CGN) deprived of potassium modeling caspase-dependent apoptosis. Finally, cbp gene repression has been observed in oxidative stress-induced death of a motomeuronal cell line. The mechanisms by which CBP levels are reduced in motomeurons of ALS mice is still unknown...

The answer is D. Organophosphates react with the active site serine residue of hydrolases such as acetylcholinesterase and form a stable phosphoester modification of that serine that inactivates the enzyme toward substrate. Inhibition of acetylcholinesterase causes overstimulation of the end organs regulated by those nerves. The symptoms manifested by this patient reflect such neurologic effects resulting from the inhalation or skin absorption of the pesticide diazinon. 

The branched-chain fatty acid, phytanic acid, is not a substrate for acyl CoA dehydrogenase due to the methyl group on its third (P) carbon (Figure 16.22). Instead, it is hydroxylated at the a-carbon by fatty acid a-hydroxylase. The product is decarboxylated and then activated to its CoA derivative, which is a substrate for the enzymes of P-oxidation. [Note Refsum disease is a rare, autosomal recessive disorder caused by a deficiency of a-hydroxylase. This results in the accumulation of phytanic acid in the plasma and tissues. The symptoms are primarily neurologic, and the treatment involves dietary restriction to halt disease progression.]... 

P-gp mediates the transport of a broad range of amphipathic hydro-phobic substrates which includes a variety of pharmacologically distinct agents used in cancer chemotherapy, hypertension, allergy, infection, immunosuppression, neurology, and inflammation (see review by Marzolini et al. (112)). 

Nauta WJH (1989) Reciprocal links of the corpus striatum with the cerebral cortex and limbic system a common substrate for movement and thought In Mueller J (Ed), Neurology and Psychiatry A Meeting of Minds, pp. 43-63. Karger, Basel. 

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