Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

Summary The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Tryptophan (Trp), serotonin (5-HT), monoamino oxidase (MAO) and 5-hydroxyindole acetic acid (5-HIAA) in brain and subesophagic ganglions of earthworms. Effects of Parathion

Summary Tryptophan, 5-HT, MAO and 5-HIAA were determined in the first 5 segments of earthworms (Oligochaetae) where the brain and subesophagic ganglions are located. Tranylcypromine (IMAO) decreased MAO activity increasing 5-HT and decreasing 5-HIAA. Motility and survival of worms were disturbed. InAllolobophora species (young worms), parathion fumigation decreased acetylcholinesterase (AChE) activity and increased Trp, 5-HT and 5-HIAA. Motility was diminished after 24 h: it worsened after 72, but returned to normal levels 40/50 days later.Publication of the National Institute of Agrarian Technology (INTA), Argentina.Acknowledgments. We are most grateful to Prof. Zlatko Tomsic (from the Lillo Institute, Tucumán) and to Leticia Alvarado (from INTA) and to Prof. Mirta P. de Matosian for earthworm classification.     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain.

The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Effect of des-Tyr1-gamma-endorphin on serotonin metabolism in rat brain regions

Intracerebroventricular (i.c.v.) administration of des-Tyr1-gamma-endorphin (0.1 and 1.0 microgram) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions.     

Suppression of the immune response by drugs interfering with the metabolism of serotonin

The work was based on the assumption that neurohumoral control of the immune response, particularly in stressed animals, involves central serotoninergic mechanisms. Rats immunized with sheep erythrocytes were stressed by repeated restraints and/or treated with a precursor of serotonin (5-hydroxytryptophan, 5-HTP) or with an inhibitor of serotonin synthesis (parachlorophenylalanine, PCPA). As expected, repeated stresses reduced the plaque-forming cell (PFC) response. Treatment with 5-HTP also reduced the PFC response, and potentiated the immunosuppressive effect of stress. This was accompanied by increased metabolism of serotonin in the brain, as indicated by increased concentration of its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebral tissue. Treatment with PCPA also suppressed the PFC response, but this suppression was accompanied by decreased levels of brain serotonin and of 5-HIAA. Plasma corticosterone levels were elevated in rats treated with PCPA. It seems that putative central effects of PCPA on serotoninergic regulation of the immune response were outweighed by its effects on corticosterone secretion and/or on lymphoid cells.     

Influence of diet on plasma tryptophan and brain serotonin levels in mice

Summary Groups of mice were maintained for up to 78 weeks on tryptophan restricted, protein restricted and control diets. Plasma tryptophan levels were significantly reduced by both forms of dietary restriction. Brain serotonin levels were significantly reduced only in mice on the tryptophan restricted diet, but not for mice on the protein restricted diet. The protein-restricted diet contains less of the large neutral amino acids which compete with tryptophan to enter the brain. It is known that protein restriction and tryptophan restriction extend lifespan. The results presented here suggest that extension of lifespan and lowering of brain serotonin are not related.     

Ultrastructural investigation of fetal rat brain hemisphere tissue in nonadherent stationary organ culture

Summary Fetal rat brain fragments grown in nonadherent stationary organ culture for 50 days have been investigated ultrastructurally. Synaptogenesis and myelin formation occurred at the same time as the corresponding time-dependent events in the developing brain in vivo. Intermediate junctions were observed between cellular processes lining a central cavity in the fragments and later associated with astrocytes at the surface. Gap junctions and tight junctions were also present. In some fragments cilia were observed in the central cavity. Subependymal basement membrane labyrinths were observed in all fragments after 10 days in culture. The ultrastructural characteristics and the tissue-like structure in general were preserved for at least 50 days in this tissue culture system. The brain fragments may therefore be a valuable supplement to existing culture methods for nervous tissue.Research fellow from the Norwegian Research Council for Sciences and Humanities. This work was supported by the Norwegian Cancer Society.     

Effect of des-Tyr1-γ-endorphin on serotonin metabolism in rat brain regions

Summary Intracerebroventicular (i.c.v.) administration of des-Tyr¹-γ-endorphin (0.1 and 1.0 μg) caused a decrease of the serotonin (5-HT) concentration of the hippocampus. The concentration of 5-HIAA and the pargyline-induced alterations in 5-HT and 5-HIAA were not affected. No effects were noticed in other brain regions. Acknowledgement. The skilful technical assistance of Ms Henny de Vos Burchart-Lodewijks and Mrs H.A. Spierenburg and J.A. Meijer is gratefully acknowledged. Des-Tyr¹-γ-endorphin was a gift of Dr. H.M. Greven, Organon International B.V., Oss, The Netherlands. To whom reprint requests should be addressed.     

Maternal stress alters monoamine metabolites in fetal and neonatal rat brain

Summary Heat-restraint stress given rats during the last week of gestation significantly altered dopaminergic dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA) and noradrenergic 3-methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG) forebrain-hypothalamic monoamine (MA) metabolites in female offspring. On gestational day 21, HVA and MOPEG were significantly higher and lower, and on postnatal day 1 all were higher. There were virtually no differences in brain MA concentrations in males. Thus MA metabolic concentrations differ in fetal-neonatal forebrain-hypothalamus as a function of sex differences and maternal stress.     

脂多糖致感染性脑水肿大鼠星形胶质细胞的活化和凋亡

目的通过观察脂多糖（Lipopolysaccharide,LPS）致大鼠感染性脑水肿后星形胶质细胞的凋亡、活化及iNOS表达情况,探讨在LPS致脑水肿中星形胶质细胞的作用。方法84只雄性SD大鼠,随机分为3组：空白对照纽（C组,n=12）;生理盐水对照纽（S组,n=12）;感染性水肿组（L组,n=60）。感染性脑水肿组又按颈内动脉注射脂多糖后6h、12h、24h、48h、72h分为5个亚组（n=12）。向颈内动脉注射脂多糖LPS150μg（0．15ml）建立大鼠感染性脑水肿模型。采用HE染色、流式细胞检测和免疫纽化染色分别观察脑组织病理改变、星形胶质细胞凋亡、胶质纤维酸性蛋白（GFAP）和iNOS表达情况。结果与C组和S组比较,L组大鼠星形胶质细胞胞体变大、突起增多;细胞内GFAP和iNOS表达增强,12h达高峰,除72h组,其余亚组均有统计学差异（P〈0．05）;各亚组星形胶质细胞凋亡增多（P〈0．05）,24h凋亡最显著。C组和S纽比较无统计学意义（P〉0．05）。结论感染性脑水肿后星形胶质细胞凋亡增加,异常活化,分泌iNOS,参与感染性脑水肿的形成,在脑水肿的发生发展中发挥重要作用。     

Regional pattern and heat-resistance of brain 5′-deoxy-5′-methylthioadenosine phosphorylase

Summary The distribution of 5-deoxy-5-methylthioadenosine (MTA) phosphorylase in 10 pig brain areas was determined. The observed regional differences of the enzymatic activity seem to reflect more the pattern of brain spermine distribution rather than that of spermidine. Moreover, comparative studies on the heat-resistance of MTA phosphorylase extracted from the whole brain of various species suggest structural differences in the enzyme molecules occurring in the brains of different animals.     

Evidence for suppression of Na-dependent Ca2+ efflux from rat brain synaptosomes by ovarian steroids in vivo

Summary The possibility that intracellular Ca²⁺, which mediates neurotransmitter release, regulation of membrane permeability, microtubule polymerization and axonal transport, is influenced by gonadal steroids via a Na–Ca exchange mechanism was examined. The resting Ca²⁺ uptake into synaptosomes was measured using crude synaptosomal pellets (P₂ fraction), isolated from the brain stem, mesencephalic reticular formation (MRF), nucleus caudatus (NC) and the hippocampus of intact, long-term ovariectomized (OVX) and OVX plus progesterone (P) or estradiol-17 benzoate (EB) treated adult female rats. Irrespective of the brain structure investigated, the uptake was 1) markedly increased in synaptosomes from OVX animals in comparison to intact controls, and 2) reduced to near control values in synaptosomes from OVX rats treated s.c. with a single dose of 2 mg P or 5 g EB. Since Ca²⁺ influx into synaptosomes was shown earlier to depend on external sodium concentration, which was the same in all experiments described in this work, the results obtained indicate that ovarian steroids modulate basal synaptic activity in the rat brain by suppressing Na-dependent Ca²⁺ efflux from the nerve cell.     

The effects of beta-endorphin on arginine-8-vasopressin and oxytocin levels in rat brain areas

Summary Measurements were made of the effects of intracerebroventricular treatment with beta-endorphin (BE; 100 ng) on the arginine-8-vasopressin (AVP) and oxytocin contents of rat hypothalamic and limbic brain areas (hippocampus, amygdala and septum). The hormone concentrations were determined by radioimmunoassay. The administration of BE resulted in a significant reduction of the AVP level in the amygdala in a naloxone-reversible manner. Naloxone (Nal) administered subcutaneously significantly increased the AVP content in the septum. The results revealed that BE and Nal had regionally specific effects on the activity of the vasopressinergic system but not on that of the oxytocinergic system in the brain.     

Aldose metabolism in developing human fetal brain and liver

Summary Aldose reductase, sorbitol dehydrogenase, and glucose-6-phosphate dehydrogenase enzyme activities were studied in human foetal brain and liver at different periods of gestation. Aldose reductase activity in liver disappears after 16 weeks of gestation whereas sorbitol dehydrogenase keeps on increasing in liver as well as in brain. In utero, some glucose metabolism may be mediated through an active sorbitol pathway in human fetuses.Acknowledgments. These studies were supported by the Indian Council of Medical Research.     

17β-estradiol in vitro affects Na-dependent and depolarization-induced Ca2+ transport in rat brain synaptosomes

Effects of 17-estradiol (E₂) in vitro on Na-dependent Ca²⁺ efflux from, and depolarization-induced Ca²⁺ uptake into, the nerve cell were studied with the use of synaptosomes isolated from the brain stem, mesencephalic reticular formation (MRF), caudate nucleus and the hippocampus of long-term ovariectomized adult female rats. It was found that E₂ (1) at a concentration of 10 nM or lower, stimulates Na-dependent Ca²⁺ efflux in the caudate nucleus and hippocampus, and does not affect the efflux in MRF and brain stem; (2) at concentrations above 10 nM has no effect on the Ca²⁺ efflux in any of the four structures investigated; and (3) produces a biphasic effect on the depolarization-induced Ca²⁺ uptake, increasing it in all structures except MRF at 10 nM concentration, and decreasing it at concentrations higher than 10 nM, irrespective of the structure investigated. These results suggest that E₂, acting at extranuclear sites, modulates synaptic transmission via alterations of Ca²⁺ transport mechanisms in nerve endings.     

Influence of age on epidermal growth factor receptor level in the rat brain

Summary The influence of age on¹²⁵I-epidermal growth factor (EGF) binding to rat brain plasma membranes was investigated. The specific binding of EGF to membranes decreased gradually with age in both male and female rats. There was no significant difference in the specific binding between males and females. Scatchard analysis of the binding data showed that the decrease in EGF binding with age was due to a decrease in the number of EGF receptors.     

Extracellular matrix and neuronal movement

Summary During brain development, both neuronal migration and axon guidance are influenced by extracellular matrix molecules present in the environment of the migrating neuronal cell bodies and nerve fibers. Glial laminin is an extracellular matrix protein which these early brain cells preferentially attach to. Extracellular glycosaminoglycans are suggested to function in restricting neuronal cell bodies and axons from certain brain areas. Since laminin is deposited along the radial glial fibers and along the developing nerve pathways in punctate form, the punctate assemblies may be one of the key factors in routing the developing neurons in vivo. This review discusses the role of laminin in neuronal movement given the present concept of the extracellular matrix molecules and their proposed interactions.     

异丙酚对大鼠内毒素脑损伤STAT3表达的影响

目的 研究异丙酚对大鼠内毒素脑损伤中信号转导子与转录激活子-3( STAT3)表达的影响,探讨异丙酚在脑损伤中的保护作用及其机制.方法 健康清洁级SD大鼠72只,雌雄不限,体重220～ 250 g,随机分为3组(n=24):L组(内毒素组)和LP组(内毒素+异丙酚组)经颈内动脉注射内毒素200 μg建立大鼠内毒素脑损伤模型,C组(对照组)经颈内动脉注射等量生理盐水,LP组颈内动脉注射内毒素后即予异丙酚100 mg/kg剂量腹腔注射.3组分别于6、12、24和48h随机处死6只大鼠,取额叶皮质,检测脑组织含水量,免疫组织化学检测P-STAT3、NF-κB和iNOS表达水平的变化,Western blot法检测大鼠内毒素脑损伤后P-STAT3蛋白表达水平的变化.结果 与C组相比,L组、LP组各时间点脑组织含水量、P-STAT3、NF-κB和iNOS表达增加(P ＜0.05,P＜0.01);与L组比较,LP组各时间点脑含水量、P-STAT3、NF-κB和iNOS表达明显减少(P＜0.05,P＜0.01).结论 异丙酚可减轻大鼠内毒素性脑损伤,机制可能与抑制脑组织磷酸化STAT3、NF-κB和iNOS表达水平上调,进而减轻炎性反应有关.