Pharmacology

Switching Drugs

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Science  19 Nov 2010:
Vol. 330, Issue 6007, pp. 1022
DOI: 10.1126/science.330.6007.1022-c
CREDIT: MORRIS ET AL., PROC. NATL. ACAD. SCI. U.S.A. 107, 19049 (2010)

Despite the long list of side effects that accompany many medications, most people still take their medicine. Perhaps this is because we know there is so much variation in drug effectiveness and side effects among individuals that we hope we will experience the benefits of the drug and be spared the side effects. Although such variation is well known, why is it so? Morris et al. sought to answer this question by comparing the spatial expression pattern of genes encoding 49 common drug targets found in the brain, in several inbred strains of mice. Many of the genes examined encode neuropsychiatric drug targets. Over 15,000 brain sections representing 203 regions of the brain were analyzed. Differences between strains occurred largely at the level of specific cell classes; for example, among neuronal subsets. Over half of the targets showed some type of interstrain variation in which brain structures they were expressed. When expression was examined across strains, strains that were more closely related showed more similar expression patterns. Gene expression in areas of the brain involved in autonomic functions, such as the hypothalamus, brainstem, and medulla, was very conserved. In contrast, the forebrain region, cortex, and hippocampus, which are involved in cognition, learning, and memory, showed the greatest interstrain expression variation. Whether such variation in gene expression also occurs in humans, and whether it influences the variation seen in the therapeutic effectiveness of drugs, still needs to be examined.

Proc. Natl. Acad. Sci. U.S.A. 107, 19049 (2010).

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