Organ-specific stem cells can be identified by the side population (SP) phenotype, which is defined by the property to effectively exclude the Hoechst 33342 dye. The ATP-binding cassette transporter ABCG2/ BCRP1 mediates the SP phenotype. Because hepatic oval cells possess several characteristics of stem cells, we examined whether they have the SP phenotype using the 2-acetylaminofluorene/partial hepatectomy (PH) model. Fluorescence-activated cell sorting analysis showed that a population of non-parenchymal cells containing oval cells, prepared on day 7 after PH, carried a significant number of SP cells, whereas that of non-parenchymal cells without oval cells, prepared on day 0 after PH, did not. Northern blot analysis using total liver RNA obtained on various days after PH showed that the expression of ABCG2/BCRP1 mRNA increased after PH, reaching the highest level on day 7, and then gradually decreased. This pattern of changes in the ABCG2/BCRP1 mRNA level was well correlated to that in the number of oval cells. Hepatocytes proliferate after liver damage such as partial hepatectomy (PH), resulting in regeneration of the liver.

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Chronic abuse of amphetamines, such as d-amphetamine (AMPH) and d-methamphetamine, results in psychological dependence, a condition in which the drug produces a feeling of satisfaction and a drive that requires periodic or continuous administration of the drug to produce overwhelming pleasure or to avoid discomfort such as dysphoria. The dysphoric state of AMPH withdrawal has been recognized as depressive syndromes, such as anhedonia, depression, anxiety, and social inhibition, in early drug abstinence. Medication for treatment of the dysphoric state is important for AMPH abusers to avoid impulsive self-injurious behavior or acts that are committed with unconscious or uncontrolled suicidal ideation. However, successful treatments for AMPH withdrawal remain elusive, since the exact molecular basis of the expression of dysphoria has not been fully elucidated. This review focuses on the molecular aspects of AMPH withdrawal as indexed by neurochemical parameters under a variety of injection regimens (for example, levels of brain monoamines and their metabolites, and gamma-aminobutyric acid, expression of genes and proteins involved in neuronal activity, and monoamine metabolism and availability) in rodent models which exhibit significant phenotypic features relevant to the syndromes of AMPH withdrawal in humans.

Oval cells of the liver participate in liver regeneration when hepatocytes are prevented from proliferating in response to liver damage. To clarify the role of oncostatin M (OSM) in the liver regeneration involving oval cells, we examined the expression of OSM and OSM-specific receptor (OSM-R) in the liver undergoing regeneration in the 2-acetylaminofluorene/partial hepatectomy model. Expression levels of OSM-R changed in correlation to the number of oval cells, and its expression was exclusively observed in oval cells. On the other hand, OSM was expressed in both oval cells and Kupffer cells. To examine the effect of OSM on the growth and differentiation of oval cells, rat oval cells (OC15-5) were incubated in conditioned medium of 293T cells expressing rat OSM cDNA. This resulted in suppression of growth, changes in morphology (microvilli and large cytoplasm with developed organelles), and expression of hepatocyte markers (albumin, tyrosine amino transferase, and tryptophan oxygenase). The effects of the conditioned medium with rat OSM were abrogated by introducing a small interfering RNA specifically targeting rat OSM-R into OC15-5 cells. These results indicate that OSM is a key mediator for inducing differentiation of OC15-5 cells into hepatocytes and suggest that the OSM/OSM-R system is pivotal in the differentiation of oval cells into hepatocytes, thereby promoting liver regeneration.