Glucocorticoid receptors (GR) mediate the direct effects of glucocorticoids released in response to stress and the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system through a negative feedback mechanism. Individuals with major mental illness, who often exhibit hypercortisolemia, may have down-regulated levels of GR mRNA. In situ hybridization for GR mRNA was performed on post-mortem specimens from patients suffering from depression, bipolar disorder, schizophrenia and from normal controls (n = 15 per group). In frontal cortex, GR mRNA levels were decreased in layers III-VI in the subjects with depression and schizophrenia. In inferior temporal cortex, GR mRNA levels were decreased in layer IV in all three diagnostic groups. In the entorhinal cortex, GR mRNA levels were decreased in layers III and VI in the bipolar group. In hippocampus, GR mRNA levels were reduced in the dentate gyrus, CA 4 , CA 3 and CA 1 in the schizophrenia group. In the subiculum, GR mRNA levels were reduced in the bipolar group. These results suggest that GR dysregulation occurs in all three major psychiatric illnesses with variability according to anatomical site. The severity and heterogeneity of this reduction may underlie some of the clinical heterogeneity seen in these disorders. Molecular Psychiatry (2002) 7, 985-994.
Oligodendrocytes of adult rodents express three different connexins: connexin29 (Cx29), Cx32, and Cx47. In this study, we show that Cx29 is localized to the inner membrane of small myelin sheaths, whereas Cx32 is localized on the outer membrane of large myelin sheaths; Cx29 does not colocalize with Cx32 in gap junction plaques. All oligodendrocytes appear to express Cx47, which is largely restricted to their perikarya. Cx32 and Cx47 are colocalized in many gap junction plaques on oligodendrocyte somata, particularly in gray matter. Cx45 is detected in the cerebral vasculature, but not in oligodendrocytes or myelin sheaths. This diversity of connexins in oligodendrocytes (in different populations of cells and in different subcellular compartments) likely reflects functional differences between these connexins and perhaps the oligodendrocytes themselves.
Within the rat ventral tegmental area (VTA), microinfusions of nicotine, the psychoactive component of cigarette smoke, produce both rewarding and aversive motivational effects. Here, a cresyl violet stained histological section showing bilateral microinjector cannulae in the rat VTA is presented. The aversive effects of intra-VTA nicotine are blocked by dopamine receptor blockade suggesting that dopamine transmits an aversive nicotine signal in the VTA. However, the rewarding effects of intra-VTA nicotine are not attenuated by this identical dopamine receptor blockade. In fact, dopamine receptor blockade dramatically potentiates the rewarding effects of nicotine and switches the motivational valence of nicotine from aversive, to rewarding.
Colorized autoradiogram of a human post-mortem section of frontal cortex showing glucocorticoid receptor mRNA hybridization signal. For more information on this topic, please see article by Webster et al on pages 985-994 of this issue.
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