Fetal glucocorticoid synthesis is required for development of fetal adrenal medulla and hypothalamus feedback suppression.

During pregnancy, fetal glucocorticoid is derived from both maternal supply and fetal secretion. We have created mice with a disruption of the Cyp11a1 gene resulting in loss of fetal steroid secretion but preserving the maternal supply. Cyp11a1null embryos have appreciable although lower amounts of circulating corticosterone, the major mouse glucocorticoid, suggesting that transplacental corticosterone is a major source of corticosterone in fetal circulation. These embryos thus provide a means to examine the effect of fetal glucocorticoids. The adrenal in Cyp11a1 null embryos was disorganized with abnormal mitochondria and oil accumulation. The adrenal medullary cells did not express phenylethanolamine N-methyltransferase and synthesized no epinephrine. Cyp11a1 null embryos had decreased diencephalon Hsd11b1, increased diencephalon Crh, and increased pituitary Pomc expression, leading to higher adrenocorticotropin level in the plasma. These data indicate blunted feedback suppression despite reasonable amounts of circulating corticosterone. Thus, the corticosterone synthesized in situ by the fetus is required for negative feedback suppression of the hypothalamus-pituitary-adrenal axis and for catecholamine synthesis in adrenal medulla.

Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.

The effects of music listening after a stressful task on immune functions, neuroendocrine responses, and emotional states in college students.

The purpose of this study was to examine the effects of listening to high-uplifting or low-uplifting music after a stressful task on (a) immune functions, (b) neuroendocrine responses, and (c) emotional states in college students. Musical selections that were evaluated as high-uplifting or low-uplifting by Japanese college students were used as musical stimuli. Eighteen Japanese subjects performed stressful tasks before they experienced each of these experimental conditions: (a) high-uplifting music, (b) low-uplifting music, and (c) silence. Subjects' emotional states, the Secretory IgA (S-IgA) level, active natural killer (NK) cell level, the numbers of T lymphocyte CD4+, CD8+, CD16+, dopamine, norepinephrine, and epinephrine levels were measured before and after each experimental condition. Results indicated low-uplifting music had a trend of increasing a sense of well-being. High-uplifting music showed trends of increasing the norepinephrine level, liveliness, and decreasing depression. Active NK cells were decreased after 20 min of silence. Results of the study were inconclusive, but high-uplifting and low-uplifting music had different effects on immune, neuroendocrine, and psychological responses. Classification of music is important to research that examines the effects of music on these responses. Recommendations for future research are discussed.

Intracerebroventricular injection of glucagon-like peptide-1 decreases monoamine concentrations in the hypothalamus of chicks.

1. We measured the concentrations of dopamine (DA), norepinephrine (NE), epinephrine (E) and 5-hydroxytryptamine (5-HT) in the hypothalamus of 21-d-old male brown-egg layer-type chicks after intracerebroventricular injection of glucagon-like peptide-1 (GLP-1). 2. The monoamine concentrations of the whole hypothalamus, paraventricular nucleus and lateral hypothalamic area were not significantly affected by GLP-1. 3. However, concentrations of DA, NE and E, but not 5-HT, in the ventromedial hypothalamic nucleus (VMH) were significantly decreased by GLP-1. 4. These observations suggest that the anorexigenic effect of GLP-1 involves catecholaminergic systems in the VMH in the chick.

Cold-stress induced the modulation of catecholamines, cortisol, immunoglobulin M, and leukocyte phagocytosis in tilapia.

The concentrations of norepinephrine in hypothalamus and norepinephrine and epinephrine in head kidney were significantly decreased in treated tilapia (Oreochromis aureus) during the time course of cold exposure (12 degrees) as compared to the control (25 degrees). The elevation of norepinephrine and epinephrine in plasma was detected earlier than that of cortisol in cold-treated tilapia. Phagocytic activity of leukocytes and the levels of plasma immunoglobulin M (IgM) were depressed in cold-treated tilapia as compared to the control group. Handling stress in the control (25 degrees) also resulted in increased plasma cortisol and decreased plasma IgM levels but not phagocytic activity. In vitro cortisol suppressed leukocyte phagocytosis in a dose (10(-12) to 10(-4) M)-dependent manner. Adrenergic agonist (phenylephrine and isoproterenol) had a significant suppression of phagocytosis only at the highest dose (10(-4) M). No effect on phagocytosis was detected in the treatment with norepinephrine and epinephrine. A combination of cortisol and isoproterenol (0.1 mM) had an additive effect in the suppression of phagocytosis. It is concluded that the cold stress modulated the changes of catecholamines and cortisol and further depressed phagocytic activity and antibody levels in tilapia. Cortisol could play a main and important role in the down-regulation of phagocytic activity. Adrenergic agonists also could interact with cortisol to further suppress immunity in tilapia.

The effect of intrastriatal injection of liposome-entrapped tyrosinase on the dopamine levels in the rat brain.

Parkinson's disease is a neurodegenerative disorder which is mainly characterized by degeneration of the dopaminergic cells in the nigro-striatal system. Due to a lowered L-tyrosine 3-monooxygenase activity, L-tyrosine is not sufficiently transformed to L-DOPA. To date the most common therapy is the administration of the dopamine precursor L-DOPA, with severe collateral effects. Therefore, the substitution of the lacking tyrosine hydroxylase with tyrosinase might be a novel therapeutical approach that would generate specifically L-DOPA from L-tyrosine. We present here evidence that stereotaxic injection of liposome-entrapped tyrosinase is able to significatively increase the levels of dopamine in the rat brain. The catecholamines L-DOPA, dopamine, L-epinephrine, L-norepinephrine were extracted by acid treatment from the brains and detected by HPLC.

[Existence of a peripheral nerve mechanism of interoceptive effects on the function of the adrenal medulla]. / O sushchestvovanii perifericheskogo nervnogo mekhanizma interotseptivnykh vliianii na funktsiiu mozgovogo sloia nadpochechnik.

In cats with decentralized solar plexus ganglia, discharges in the central stumps of post-ganglionic nerve branches running from the celiac and superior mesenteric ganglia to the adrenal glands, were studied. An obvious peripheral neural connection through C-afferents of peripheral origin was found to exist among the spleen, stomach, small intestine and the adrenals. Electrical stimulation of the central stumps of splenic or superior mesenteric nerves increased adrenaline, noradrenaline and dopamine contents in the adrenals. Simultaneously there was an increase in the catecholamine concentration in the myocardium, medulla oblongata and hypothalamus, indicating the release of hormones into the blood flow and their uptake by the tissues. A peripheral neural mechanism seems to exist which mediates interoceptive influences on the adrenal medullary function.

Adrenaline synthesizing nerve cells in the medulla of normotensive and hypertensive rats.

1. We have studied the number and distribution of adrenaline synthesizing nerve cells in the medulla oblongata of the rat, using a combination of immunofluorescence to visualize the enzyme phenylethanolamine-N-methyltransferase (PNMT) and catecholamine fluorescence to detect central catecholamines. 2. The distribution of adrenaline synthesizing nerve cells was similar in normotensive (Wistar Kyoto) rats, spontaneous hypertensive rats, and stroke-prone rats. Few of the cells visualized by PNMT immunofluorescence were detected by the Faglu fluorescence method for catecholamines. The C1 (ventrolateral) and C2 (dorsomedial) groups of PNMT cells were anatomically distinct from the A1 and A2 groups of catecholamine fluorescent cells and lay rostral to these cells within the medulla. There was a third group of adrenaline synthesizing cells close to the midline in the rostral medulla, and we have called this the C3 group. 3. There was a 32% increase in the number of PNMT cells in the medulla of 4-week-old stroke-prone rats. 4. PNMT enzyme activity in a cross-segment of the medulla containing the adrenaline synthesizing cells was also increased by 30% in both spontaneous hypertensive rats and stroke-prone rats.

Catecholamine synthesizing enzymes in brain stem and hypothalamus during the development of renovascular hypertension.

The activities of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) have been measured in brain stem and hypothalamic nuclei during the development of renovascular hypertension. TH activity fell at 72 h in the posterior hypothalamic and peri- and paraventricular nuclei of the hypothalamus, but had returned to control levels by 7 days. PNMT activity was raised in the nucleus of the solitary tract at 7 days and was also elevated in the nucleus of the solitary tract, parahypoglossal nucleus, locus coeruleus and cerebellar cortex at 4 weeks. No change in PNMT was noted in hypothalamus. It appears from these results that both central noradrenergic and adrenergic pathways are involved in the development of this model of experimental hypertension.

Hypothalamic adrenaline synthesis after stimulation of the medial forebrain bundle.

1 The problem of whether locally released noradrenaline can be methylated to adrenaline in the hypothalamus has been investigated. 2 During stimulation of the medial forebrain bundle (MFB) the hypothalamic adrenaline content increased somewhat, but the increase was not statistically significant (13%, mean of 10 experiments). 3 After inhibition of the activity of monoamine oxidase and catechol-O-methyltransferase this increase was much larger (80%, mean of 9 experiments). 4 Adrenalectomy did not prevent the rise in hypothalamic adrenaline after stimulation of the MFB. These results suggest that noradrenaline released during activity of noradrenergic hypothalamic structures may be methylated to adrenaline in the hypothalamus.

Biochemical and morphologic study of catecholamine metabolism in spontaneously hypertensive rats.

Catecholamines and catecholamine-synthesizing enzymes have been studied quantitatively in specific brain areas of spontaneously (genetically) hypertensive rats by means of a combination of sensitive enzymatic-isotopic methods and a microdissecting technique. Changes in catecholamine metabolism were found to be localized to regions of the brain implicated in the regulation of blood pressure. Noradrenaline levels were decreased in specific nuclei of the anterior hypothalamus and in the nucleus interstitialis striae terminalis ventralis. The activity of the adrenaline-forming enzyme, phenyl-ethanolamine-N-methyl transferase, was increased in the A1 and A2 areas of the brain stem. These results implicate catecholamine-forming neurons in the hypothalamus and brain stem in the development of spontaneous hypertension in rats.