Role of noradrenergic fibers of the preoptic area in regulating sleep

The preoptic area (POA) has noradrenergic (NE) terminals, and this area controls sleep apart from body temperature and reproduction. The destruction of catecholaminergic (CA) terminals in the POA produced a decrease in sleep in rats. This effect was shown to be due to the destruction of NE and not dopaminergic terminals. The rats, which were hyperthermic after the destruction of CA fibers in the POA, preferred a lower ambient temperature. Though they were unable to have normal amount of sleep after lesion, it did not affect their behavioral thermoregulation. Acute total sleep deprivation for 48 h led to a significant decrease in noradrenaline, increase in the level of metabolites of monoamines, and an enhancement in the number of dendritic spines at the medial preoptic area (mPOA). Enhanced sleep pressure during sleep deprivation could have led to a higher release of noradrenaline, and an increase in dendritic spines in the mPOA. Arousal was produced by application of noradrenaline at the mPOA, whereas the alpha antagonists produced sleep in free-moving rats. This was in contrast to the increased wakefulness produced by the destruction of NE terminals. As wakefulness and sleep, respectively, were induced on local application of alpha-2 antagonist and agonists, it was suspected that the noradrenaline and alpha antagonists might have acted on the alpha-2 receptors, which are predominantly present on the pre-synaptic terminals. Sleep produced by noradrenaline, which was locally applied at the mPOA, after destroying the NE terminals, further confirmed this possibility. Hypothermia and sexual arousal produced by application of alpha- and beta-adrenergic agonists at the mPOA would have contributed towards the wakefulness induced by these drugs in normal rats. Thus, the available evidence shows that the NE fibers in the POA are involved in the induction of sleep.     

Functional MRI shows activation of the medial preoptic area during sleep

Changes in the activity of the basal forebrain sleep regulating areas were studied noninvasively in conscious rats by employing functional magnetic resonance imaging (fMRI). Sleep-wakefulness (S-W) stages were identified with the help of electrophysiological recordings carried out simultaneously. An increase in the signal intensity was observed in the medial preoptic area (mPOA) during sleep indicating a heightened activity of neurons in this area. In some rats, there was a decrease in the activity of the fronto-parietal cortex. The sleep-induced increase in activity in the mPOA and decrease in the fronto-parietal cortex are in relation to their levels in the awake state. The findings helped to localize the critical area for the maintenance of slow wave sleep at the mPOA. These results further corroborate some of the previous suggestions based on neurotoxic lesion, chemical stimulation and electrophysiological recordings.     

Sustained activation of the HER1-ERK1/2-RSK signaling pathway controls myoepithelial cell fate in human mammary tissue

Human mammary glands arise from multipotent progenitor cells, which likely respond both to cell-autonomous and to extrinsic cues. However, the identity of these cues and how they might act remain unclear. We analyzed HER1 ligand effects on mammary morphogenesis using a three-dimensional organoid model generated from human breast tissue that recapitulates both qualitatively and quantitatively the normal ductal network in situ. Strikingly, different HER1 ligands generate distinct patterns of cell fate. Epidermal growth factor (EGF) causes a massive expansion of the myoepithelial lineage. Amphiregulin, in contrast, enables normal ductal development. These differences cannot be ascribed to preferential apoptosis or proliferation of differentiated cell populations, but are dependent on HER1 signal intensity. Inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) effector RSK prevents the EGF-induced myoepithelial expansion. Notably, mouse mammary organoids are much less responsive to HER1 ligands. Little is known about the myoepithelial lineage or about growth factor effects on mammary progenitor differentiation, and our studies provide an important window into human mammary development that reveals unexpected differences from the mouse model.     

Extrinsic Compression of the Left Coronary Ostium by the Pulmonary Trunk: Management in a Case of Eisenmenger Syndrome

Extrinsic compression of the left main coronary artery by a massively dilated pulmonary artery in patients who have severe pulmonary hypertension can lead to significant myocardial ischemia. A 58-year-old man with a large patent ductus arteriosus and Eisenmenger syndrome presented with angina at rest and worsening heart failure of 3 months'' duration. The new symptoms were recognized to be secondary to extrinsic compression of the left main coronary artery ostium by a dilated main pulmonary artery and were successfully relieved by the placement of a metallic stent in the affected segment of the left main coronary artery. Multislice computed tomographic imaging after 6 months showed stent patency and the intimate relation of the stented vessel to the dilated main pulmonary trunk. We discuss diagnostic and management issues pertaining to this uncommon clinical entity.Key words: Angina pectoris/etiology, angioplasty, transluminal, percutaneous coronary, constriction, patho-logic/etiology, coronary stenosis/etiology, dilatation, pathologic/complications, ductus arteriosus, patent, Eisenmenger complex/ complications, hypertension, pulmonary/complications, stents, tomography, X-ray computedA pulmonary trunk dilated by severe pulmonary artery hypertension (PAH) can compress the aortic ostium of the left main coronary artery (LMCA).¹ If the primary disease process causing PAH cannot be reversed, progressive coronary narrowing can lead to left ventricular myocardial dysfunction, angina, and worsening of heart failure.² We report the case of a 58-year-old patient with a large patent ductus arteriosus and Eisenmenger syndrome who presented with angina at rest and worsening of heart failure due to left ventricular dysfunction. Coronary angiography showed extrinsic compression of the LMCA, at its origin, by a dilated pulmonary trunk. Stenting of the LMCA resulted in immediate relief of angina and led to symptomatic improvement.     

Perirhinal cortex lesions delay ejaculation in rats

Afferents from the perirhinal cortex (PRh) form a major input to the hippocampal formation, which is known to be involved in sexual behavior in rodents. But there is a lacuna in literature regarding the role of the PRh in sexual behavior. Bilateral neurotoxic lesions of the PRh delayed the ejaculation latency and prolonged the mean inter-intromission interval significantly, suggesting a facilitatory role of the PRh in male rat sex behavior.