Central L-ornithine, but not polyamines, induces a hypnotic effect in neonatal chicks under acute stress.

To clarify whether L-ornithine and/or its metabolite involves sedative and hypnotic effects under social separation stress, the effects of intracerebroventricular (i.c.v.) injection of L-ornithine and polyamines (putrescine, spermidine and spermine) were compared in chicks. Birds were injected i.c.v. with 0.5 mumol of L-ornithine, putrescine, spermidine, spermine or saline (control). After injection, chicks were immediately separated from the flock and monitored for the number of distress vocalizations and various postures. L-Ornithine greatly attenuated the stress response and caused sedative and hypnotic effects. Among the polyamines, only putrescine attenuated distress vocalizations but did not induce sleep. In conclusion, the sedative and hypnotic effect of L-ornithine was mainly induced by L-ornithine itself, while the polyamines contributed to the sedative, but not hypnotic, effect under social separation stress.

L-DOPA attenuates hyperactivity of Roborovskii hamsters.

The Roborovskii hamster (Phodopus roborovskii) has been shown to have high locomotor activity (hyperactivity) and low dopamine concentrations in the brain. We hypothesized that low brain dopamine concentrations play a role in the pathogenesis of hyperactivity. In this study, therefore, we investigated the effects of L-DOPA (L-3,4-dihydroxyphenylalanine), the precursor of dopamine, on the locomotor activity of Roborovskii hamster to verify the above hypothesis. An open field test was employed to measure the locomotor activity. Administration of L-DOPA dose-dependently decreased locomotor activity including distance of path and time spent moving. L-DOPA increased the brain concentration of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid. Concurrently, L-DOPA caused increase of norepinephrine, decrease of serotonin, and atypical alteration of their metabolite concentrations. These findings mainly suggest that in Roborovskii hamsters, a low level of brain dopamine neurotransmission is one of the reasons for hyperactivity, and hyperactivity can be attenuated by L-DOPA.

l-Serine induces sedative and hypnotic effects acting at GABA(A) receptors in neonatal chicks.

Intracerebroventricular injection of l-serine has been shown to have sedative and hypnotic effects on neonatal chicks exposed to acute stressful conditions. However, the mechanism by which l-serine induces these effects is unclear. The present study was conducted to clarify the mechanism by l-serine. The involvement of gamma-aminobutyric acid (GABA)(A) receptors on the effect of l-serine was investigated using the GABA(A) receptor antagonist picrotoxin. Co-administration of picrotoxin attenuated the sedative and hypnotic effect of l-serine. Further, we also investigated the involvement of glycine receptors since l-serine is suggested to act as the alpha-homomeric glycine receptor agonist. Glycine similarly induced sedative and hypnotic effects in chicks, but its effect was attenuated by the glycine receptor antagonist strychnine. Therefore, whether the effect of l-serine was mediated through the glycine receptor was investigated using l-serine and strychnine. The effect of l-serine was inhibited by picrotoxin, but not strychnine. It appears that l-serine induces sedative and hypnotic effects by enhancing inhibitory neurotransmission via GABA(A) receptors.

mRNA expression of lysyl oxidase and matrix metalloproteinase-12 in mouse skin.

Elastic fibers in the dermis play an important role in skin elasticity. The desmosine crosslinking structure constructed of lysyl oxidase (LOX) in elastic fibers contributes to elasticity, while elastic fibers are primarily degraded by one of the matrix metalloproteinases (MMPs), MMP-12. We investigated the gender differences and diurnal variation of these enzymes. Gender-based differences in LOX mRNA expression were detected, and were significantly lower in females. In contrast, higher MMP-12 mRNA expression was observed in the light period, suggesting that elastic fibers might be degraded in the light rather than the dark period.

Different locomotor activities and monoamine levels in the brains of Djungarian hamsters (D. sungorus) and Roborovskii hamsters (D. roborovskii).

Two species of the genus Phodopus, Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii), differ in their behavior. The Roborovskii hamster has high locomotor activity (hyperactivity) compared to the Djungarian hamster. In this study, we compared locomotor activity of the hamsters in different environments, and compared their brain monoamine and metabolite levels to identify the mechanism by which both hamsters move differently. Activity of Roborovskii hamsters was significantly higher than Djungarian hamsters in the open field, while no difference was observed in their home cage. Dopamine (DA) and serotonin (5-HT) levels in the whole brain of Roborovskii hamster were significantly lower and their metabolic turnover rates were significantly higher than those of the Djungarian hamster. We conclude that the difference in activity under the novel environment between both species is partly, but not entirely, explained by the difference in monoamine levels and their metabolism in the brain.

VEGF-induced antidepressant effects involve modulation of norepinephrine and serotonin systems.

Throughout life, we are exposed to a variety of stresses, which may be inevitable and noxious sometimes. During evolution, animals must have acquired some physiological means to counteract stress. Vascular endothelial growth factor (VEGF) is an angiogenic and neurogenic factor, which has been shown to elicit antidepressant-like effects in response to different external stimuli, potentially functioning as an anti-stress molecule. However, it remains largely unknown how VEGF modulates mood-related behaviors. To investigate molecular correlates, we analyzed monoaminergic systems of VEGF transgenic mice that display antidepressant-like behavior. Immunostaining showed that overall morphologies of monoaminergic nuclei and their processes were normal. However, we found imbalances in brain monoamine contents, in which the levels of norepinephrine and serotonin, but not dopamine, were decreased exclusively in the regions where VEGF was expressed. The turnover of norepinephrine showed a marked increase and serotonin turnover showed a modest reduction, whereas dopamine turnover was not affected. The protein levels of tyrosine hydroxylase and tryptophan hydroxylase, the rate-limiting enzymes of catecholamine and serotonin synthesis, remained constant. The mRNA levels of monoamine receptors were generally similar but adrenergic receptors of ADRα1A and ADRß1 were down-regulated. Behavioral tests showed that serotonin- or norepinephrine-selective antidepressant drugs failed to additively enhance antidepressant-like behaviors, whereas monoamine depleting drugs attenuated VEGF-mediated antidepressant-like effect. These data suggest that VEGF-induced antidepressant-like effects involve modulation of norepinephrine and serotonin systems.

Chronic L-tyrosine alters the locomotor activity and brain monoamine levels in Roborovskii hamsters.

The Roborovskii hamster (Phodopus roborovskii) has high locomotor activity (hyperactivity) and low dopamine levels in the brain compared with the congeneric Djungarian hamster (Phodopus sungorus). To clarify the efficacy of dietary l-tyrosine in ameliorating signs of hyperactivity, we investigated the effects of chronic administration of l-tyrosine, the primary precursor of dopamine, on locomotor activity and brain monoamine levels in Roborovskii hamsters. Chronic supplementation of l-tyrosine had no effect on locomotor activity in the open field, but did decrease locomotor activity in the home cage. Tyrosine increased dopamine and norepinephrine turnover rates and decreased in serotonin turnover rate in the brain. These findings suggest that long-term feeding of l-tyrosine may be effective in ameliorating signs of hyperactivity.

Central l-proline attenuates stress-induced dopamine and serotonin metabolism in the chick forebrain.

Using microdialysis, we investigated the effect of l-proline on monoamine release in the medio-rostral neostriatum/hyperstriatum ventrale (MNH) of freely moving and restricted chicks. A 30 min handling-stress resulted in a significant increase in extracellular homovallinic acid (HVA), a dopamine metabolite, and 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, in the MNH. l-Proline, perfused through the microdialysis probe into the MNH during the stressed condition, significantly attenuated the average dialysate concentration of HVA produced by handling-stress. Handling-stress resulted in a significant increase in 5-HIAA levels in the control group, which were attenuated by profusion with l-proline. l-Proline did not significantly modify basal concentrations of HVA or 5-HIAA in the MNH during control conditions. These results show that perfusion of l-proline modified the turnover/metabolism of dopamine and serotonin in the MNH caused by handling-stress.