Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

The neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a positive modulator of GABA_A receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic–pituitary–adrenal axis and elevates 3α,5α-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3α,5α-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3α,5α-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3α,5α-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3α,5α-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3α,5α-THP following ADX. In subcortical regions, 3α,5α-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3α,5α-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3α,5α-THP levels in several subcortical regions; however, the adrenal glands contribute to 3α,5α-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3α,5α-THP induction by ethanol is not due to a lack of colocalization of 3α,5α-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).     

Cortical activation and language task difficulty in aphasia

Background: Previous research using functional MRI (fMRI) suggests changes in cortical activation as a function of increased task difficulty. This relationship has not been explored in persons with aphasia even though it may have significant implications for pre- and post-treatment interpretation of fMRI data.Aims: The purpose of this exploratory study was to investigate the relationship between changes in language task difficulty and cortical activation in persons with aphasia.Methods & Procedures: Four persons with chronic anomic or Broca's aphasia and four matched control participants underwent fMRI while performing a picture–word matching task.Outcomes & Results: Compared to the more difficult task condition, all participants performed with greater accuracy on the easier condition. Moreover, greater mean blood oxygenated level dependent (BOLD) signal intensity and area recruitment were noted during the more difficult condition for three out of four persons with aphasia as well as three of the four controls. The increase in cortical activity was mainly noted in the superior temporal and posterior inferior frontal lobes.Conclusions: The present findings mirror those found in previous studies of normal subjects in that cortical activation increased in parallel to task difficulty for most of our participants. It is unclear what mechanism accounts for this effect; this phenomenon might need to be considered in future fMRI studies of neural plasticity associated with aphasia treatment.     

The Evolving Role of Partial Breast Irradiation in Early-Stage Breast Cancer

Whole breast irradiation (WBI) over 5–7 weeks has long been considered standard adjuvant treatment after breast-conserving surgery. Recently the concept of irradiating the whole breast has been challenged by accelerated partial breast irradiation (APBI), which exclusively targets the lumpectomy site plus margin. We review the evidence supporting APBI from modern clinical trials, the pros and cons of various APBI techniques, and the controversies regarding the applicability of APBI to specific patient groups.