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Notes: Abstract: Diabetic animals exhibit altered neurotransmission in brain monoaminergic systems. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline, and serotonin transporter (DA-T, NA-T, and 5-HT-T, respectively) mRNAs in the brains of alloxan- and streptozotocin-diabetic rats. The expression of DA-T mRNA is decreased in 1- (−11%) and 4-(−17%) week alloxan-diabetic and 4- (−9%) and 8-(−20%) week streptozotocin-diabetic rats in the ventral medial bundle. The expression of NA-T mRNA is decreased in the locus coeruleus of 8- (−26%) week streptozotocin-diabetic rats, in the noradrenergic A1 cell group of 4-(−27%) week alloxan- and 8- (−25%) week streptozotocin-diabetic rats, and in the noradrenergic A2 cell group of 1- (−21%) and 4- (−28%) week alloxan-diabetic and 4- (−27%) and 8- (−25%) week streptozotocin-diabetic animals. The expression of 5-HT-T mRNA in the dorsal raphe nucleus is increased in 1- (+14%) and 4- (+44%) week alloxan- and 4- (+28%) and 8-(+44%) week streptozotocin-diabetic rats. The expression of each of the three monoamine transporter genes may be differentially regulated in diabetes and dependent on the duration of diabetes. Altered monoamine transporter gene expression may possibly contribute to the observed dysfunctions in brain monoamine transmission in chronic diabetes.

Notes: We report the first demonstration of CdTe metal-semiconductor field-effect transistors. These transistors were fabricated using n-type CdTe films grown by photoassisted molecular beam epitaxy. Using this new film deposition technique, it is possible to obtain highly activated n-type or p-type films suitable for device applications. In the present work, transistor structures with 5 or 100 μm gate lengths having channel dopings in the range from 2×1016 to 2×1017 cm−3 were fabricated and tested. The 5 μm gate devices have transconductances as large as 10 mS/mm and pinch-off voltages of 4.0 V.

Notes: The piezomodulated reflectivity spectra of CdMnTe-CdTe superlattices grown by photoassisted molecular-beam epitaxy reveal signatures associated with excited confined quantum states. The energies of these signatures are in excellent agreement with the predicted energies for heavy-hole and light-hole states calculated using a Kronig–Penney model in which strain effects are included. For comparison, we present calculations for the cases of a zero valence-band offset and a small valence-band offset which scales with Mn concentration.

Notes: The neuropeptide oxytocin has long been known as a potent contractor of the uterus. However, it has remained difficult to attribute a definite role for neurohypophysial oxytocin in either the initiation or continuation of labour (1). Most recently, Lefebvre and colleagues (2) have suggested that oxytocin produced in the uterus, rather than in the hypothalamus, may be more important in parturition since at term the uterus of the rat contains 70-fold more mRNA for oxytocin than the hypothalamus, and this disappears at about the time of parturition. Despite the high levels of mRNA the uterus contains only nanogram quantities of immunoreactive oxytocin per gram wet weight at term (2), compared to microgram quantities present in the pituitary (3,4). Here we show that activation of the neurohypophysial oxytocin system occurs, as reflected by expression of immunoreactivity for Fos in the hypothalamic supraoptic nucleus, and that this activation is indeed critical for normal parturition, since its inhibition results in a significant prolongation of parturition. In addition, we present evidence that pulsatile delivery of oxytocin into the circulation is important for the efficient progress of parturition, indicating that a major role of the neuronal circuits regulating oxytocin secretion for parturition, as is already known for suckling, is to produce an appropriately patterned hormonal output for efficient biological action.

Notes: Supraoptic nucleus oxytocin neurone activity and secretion are inhibited in late pregnancy and parturition by endogenous opioids. Here, we investigated alterations in the projections and gene expression of β-endorphin/pro-opiomelanocortin neurones in the arcuate nucleus in the pregnant rat. All regions of the arcuate nucleus were found to contain cells immunoreactive for β-endorphin fluorescent microbeads retrogradely transported from the supraoptic nucleus, and double-labelled neurones (β-endorphin plus microbeads), showing that β-endorphin neurones throughout the arcuate nucleus project to the supraoptic nucleus. There was an increase in the number of β-endorphin-immunoreactive cells in the arcuate nucleus and an increase in the density of β-endorphin fibres within the supraoptic nucleus and peri-supraoptic region in late pregnancy and parturition, suggesting enhanced expression of β-endorphin and increased β-endorphin innervation of the supraoptic nucleus. Pro-opiomelanocortin mRNA expression in the arcuate nucleus increased in late compared to early pregnancy: the number of positive neurones significantly increased in the caudal region. Fos expression (an indicator of neuronal activation) in the arcuate nucleus was colocalized in β-endorphin neurones in both proestrus and parturient rats, but the number of positive cells did not increase during parturition, suggesting lack of activation of β-endorphin neurones at birth. Thus, β-endorphin cells in the arcuate nucleus project to the supraoptic nucleus and increased innervation during pregnancy may explain the enhanced endogenous opioid inhibition of oxytocin neurones.

Notes: Opioid peptides are present in nerve terminals in the rat neural lobe where they partially coexist with vasopressin. Morphological findings suggest that these neuropeptides are released onto pituicytes, which is in agreement with a possible role for the pituicyte in oxytocin and vasopressin release from the neural lobe.Pituicytes in culture respond to vasopressin with a mobilization of calcium from intracellular stores. In the present study this vasopressin induced increase in intracellular free calcium levels was both delayed and decreased by pre-exposure to dynorphin 1–17, while dynorphin 1–17 by itself did not affect basal calcium levels. All effects of dynorphin 1–17 could be blocked with naloxone. The present results suggest that opioid receptors are present on pituicytes and are coupled to a second messenger pathway by which opioid peptides may inhibit inositol phosphate dependent calcium mobilization by other neuropeptides, such as vasopressin.

Notes: Lactating rats show reduced oxytocin release compared with virgin female rats in response to a variety of stimuli, including stress and osmotic stimulation. We sought to establish whether this is a consequence of a reduced response in the oxytocin cells, or of a change in stimulus-secretion coupling at the level of the neurosecretory terminals in the neural lobe. Blood sampling experiments in anaesthetized rats showed that systemic administration of cholecystokinin resulted in significantly less oxytocin release in lactating rats than in virgin female rats. Electrophysiological recordings of single cells in the supraoptic nucleus, however, showed no difference in the responsiveness of oxytocin cells to this stimulus. Oxytocin release evoked by electrical stimulation or by depolarization with high potassium solutions was lower in isolated neural lobes from lactating rats than in glands from non-lactating rats, whereas evoked vasopressin release was similar in the two groups. The lactating rat neural lobes had a reduced oxytocin content: to study the consequences of depletion we compared hormone release evoked by electrical stimulation in vitro in neural lobes from normal male rats, and from male rats given 2% NaCI to drink for 2 or 4 days. Saline drinking resulted in a reduction in gland content of both oxytocin and vasopressin, and the evoked release of both hormones was also significantly reduced when expressed as a percentage of the gland content, as was also seen for oxytocin release for glands from lactating rats. Finally, measurement of the extracellular potassium response to stimulation of the isolated neural lobe as an index of the excitability of neural lobe neurosecretory axons was unchanged in lactating rats compared with virgin female rats. Together, the data indicate that reduced oxytocin release observed in lactating rats is a simple consequence of reduced oxytocin content in the neural lobe rather than of a reduced excitability of the oxytocin neurons.

Notes: We have investigated the influence of endogenous opioids on oxytocin secretion during pregnancy. In blood-sampled consciousrats on days 18 and 21 of pregnancy plasma oxytocin concentration, measured by radioimmunoassay, was significantly increased compared to non-pregnant or post-partum rats. On days 15, 18 and 21 of pregnancy, but not in non-pregnant, early pregnant or post-partum rats, the opioid antagonist naloxone caused a significant increase in plasma oxytocin compared to vehicle injection, indicating activation of an endogenous opioid restraint over oxytocin secretion.Electrically stimulated neural lobes isolated from 16- and 21-day pregnant rats released more oxytocin than those from non-pregnant rats. However, naloxone (10−5 M) was less effective at potentiating, and the k-opioid agonist U50,488 (10−5 M) was less effective at inhibiting, stimulated release at the end of pregnancy than in non-pregnant rats suggesting desensitization of oxytocin nerve terminals to actions of endogenous opioids. Neural lobes from male rats drinking 2% saline for 4 days also showed desensitization of oxytocin nerve endings to naloxone.Neither neural lobe content of dynorphin A(1–8), an endogenous k-opioid, nor prodynorphin mRNA expression, measured by in situ hybridization histochemistry in the supraoptic nucleus altered during pregnancy. However, neural lobe content of Met5enkephalin significantly decreased by day 21 of gestation suggesting enhanced release. We conclude that an endogenous opioid, possibly a product of proenkephalin A in oxytocin cells may be responsible for auto-inhibition of oxytocin release during gestation, and that this mechanism desensitizes in late pregnancy at a time when other opioid inputs to the oxytocin neurons become activated to provide an overall increase in opioid restraint of the system. The changes in opioid input through pregnancy may be involved in initiation and regulation of oxytocin secretion at parturition. A similar opioid mechanism, but possibly involving dynorphin, could explain desensitization in saline drinking rats and indicates that desensitization may be a consequence of chronic activation of secretion from the oxytocin nerve terminals rather than a phenomenon peculiar to pregnancy.