Developmental profile of glucocorticoid binding to synaptic plasma membrane from rat brain

Plasma prolactin levels were measured in free-living breeding adult and immature (pre-breeding) macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins at Bird Island, South Georgia (54 degrees S, 38 degrees W). Macaroni and gentoo penguins first breed at 5-6 and 2 years of age, respectively. In adult birds, of both species, prolactin was low (< 1.0 microgram. liter-1) during the courtship period and then increased during early (gentoo) to mid (macaroni) incubation (to 3.9-4.7 and 2.4-3.5 micrograms.liter-1, respectively), remaining elevated until the creche period, by which time continuous nest attendance by the adults had ceased. This pattern is similar to that seen in other altricial species and is consistent with delayed onset of brood patch development and full incubation efficiency, which has been previously reported in penguins. Adult female macaroni penguins showed a marked, but transient, increase in prolactin concentrations within 24 hr of the first egg being laid (from 1.7 to 7.0 micrograms.liter-1), plasma levels decreasing following clutch completion (to prelaying levels) before increasing again during incubation. Elevated plasma prolactin levels occurred in all age classes of immature (nonbreeding) birds in both macaroni (1- to 5 year-olds) and gentoo (1-year-olds) penguins. However, compared to that in adult birds, the increase in prolactin was more transient in immatures, a smaller proportion of immatures had detectable prolactin levels at each stage of the breeding cycle, and, at least in 1- and 2-year-olds, absolute levels of prolactin were lower.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developmental expression of the tenascin-C is altered by hypothyroidism in the rat brain

Tenascin-C is an extracellular matrix glycoprotein involved in cell adhesion and migration, and neurite outgrowth. Since these processes have been found to be under thyroid control in the developing rat brain, we have investigated the effect of congenital hypothyroidism on tenascin-C expression. At birth, in situ hybridization studies in hypothyroid rats show an abnormal up-regulation of tenascin-C in some areas (caudate-putamen, geniculate nuclei, ependymal epithelium of the lateral ventricles, hippocampus) and down-regulation in others (occipital and retrosplenial cortex, subiculum). With subsequent development, hypothyroid animals show higher tenascin-C expression also in the upper layers of the cerebral cortex and subplate, and the Bergmann glia of the cerebellum. Significantly, thyroxine treatment of hypothyroid rats led to normalization of tenascin-C levels in most areas. In agreement with the messenger RNA data, hypothyroid rats contain an uniformly higher level of immunoreactive tenascin-C protein throughout the brain, particularly in the cerebellum. Suggesting a direct cellular effect, thyroid hormone also decreases tenascin-C expression in two glial cell lines (C6, B3.1) expressing thyroid receptors. Our results show that congenital hypothyroidism causes specific alterations in the pattern of tenascin-C expression in the rat brain which may at least partially be responsible for some of the developmental disturbances observed in this syndrome.     

Comparison of O6-methylguanine-DNA methyltransferase activity in brain tumors and adjacent normal brain

We assayed the activity of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in 60 human brain tumors to assess the effects of tumorigenesis in brain on DNA repair capability. Activity was not detectable (< 0.5 fmol/10(6) cells, i.e., < 300 molecules/cells) in 27% of the tumors. Measurable MGMT varied by more than 2 orders of magnitude, 0.5-104.1 fmol/10(6) cells. Mean tumor MGMT levels did not differ between the sexes but did vary widely between diagnostic groups. A significant inverse correlation was observed between tumor MGMT activity and patient age. We also assayed MGMT activity in overlying, histologically tumor-free brain resected with 25 tumors. Of these samples, 52% had no detectable MGMT activity, and the remainder had activity comparable to that in tumors ranging from 0.7-21.8 fmol/10(6) cells. MGMT activity in normal brain was also inversely correlated with patient age. For 15 of 25 (60%) paired samples, tumor activity was 2 to > 38-fold greater than that of normal brain; for 4 pairs (16%) tumor activity was 2.5 to > 17-fold lower than that of normal brain; the remaining 6 (24%) had no detectable activity in both tumor and normal tissue. These differences in the magnitudes and distributions of activities for tumor versus normal brain tissue were significant (P = 0.02), demonstrating that tumorigenesis in brain is often accompanied by marked elevation of MGMT.     

Heterogeneous distributions of histamine H3, dopamine D1 and D2 receptors in rat brain

The changes of the histamine H3 and dopamine D1 or D2 receptor binding sites induced by quinolinic acid treatment were studied in order to discriminate the comparative distribution. This treatment resulted in similar decreases in histamine H3 and dopamine D1 receptor binding sites in the striatum and ipsilateral substantia nigra. Dopamine D2 receptor binding sites were relatively well conserved, whereas H3 receptors decreased considerably. These results suggest that histamine H3 and dopamine D1 receptor binding sites are localized on the striatonigral projection neurones which are together sensitive to quinolinic acid, and that the distributional compartment of dopamine D2 receptor binding sites is quite different from those of histamine H3 and dopamine D1 receptors.     

Developmental distribution of glycosaminoglycans in embryonic rat brain: relationship to axonal tract formation

Glycosaminoglycans, the sugar moieties of proteoglycans, modulate axonal growth in vitro. However, their anatomical distribution in relation to developing axonal tracts in the rat brain has not been studied. Here, we examined the immunohistochemical distribution of chondroitin-6-sulfate and chondroitin-4-sulfate, two related glycosaminoglycan epitopes, which are present in three types of glycosaminoglycans: chondroitin sulfate C, chondroitin sulfate A, and chondroitin sulfate B. Further, we compared their distribution pattern to that of axonal tract development. Both glycosaminoglycan epitopes showed a heterogeneous spatiotemporal distribution within the developing rat brain. However, the expression of chondroitin-4-sulfate was more restricted than that of chondroitin-6-sulfate, although both epitopes were detected from embryonic day 13 until the day of birth, overlapping in many regions of the central nervous system including cortex, hippocampus, thalamus, and hindbrain. After birth, the levels of expression of both glycosaminoglycan epitopes progressively decreased and were practically undetectable after the first postnatal week. The expression of chondroitin-6-sulfate and, to a lesser extent, that of chondroitin-4-sulfate, was preferentially associated to the extracellular matrix surrounding specific axon bundles. However, the converse association was not true, and several apparently similar types of axon developed on a substrate devoid of both types of glycosaminoglycan epitopes. These results provide an anatomical background for the idea that different types of glycosaminoglycans may contribute to establish the complex set of guidance cues necessary for the specific development of defined axon tracts in the central nervous system.     

The uniquely distributed isoprenylated protein methyltransferase activity in the rat brain is highly expressed in the cerebellum

Isoprenylated protein methyltransferase, the enzyme which catalyzes the reversible methylation of signal transducing G-proteins was studied in nine brain regions of the rat brain using S-farnesyl cysteine analogs as substrates. Enzyme activity, as determined with N-acetyl-S-farnesyl-L-cysteine (AFC) was found in the nuclear, synaptosomal and microsomal fractions of all brain regions but not in the cytosol. The enzyme is a unique methyltransferase with respect to its brain distribution. The rank order of activity of the enzyme is cerebellum > midbrain > medulla > forebrain regions, where activities in cerebellar synaptosomal and nuclear fractions (28-32 pmol AFC [methyl-3H]ester formed/min/mg prot) are 20 to 30 times higher than those of the corresponding fraction of the forebrain regions. This distribution is reminiscent of that of neurotransmitter receptors and signal transduction molecules and suggests a regulatory role for the enzyme, particularly in the cerebellum.     

Developmental regulation of the brain polyamine-stress-response

A transient increase in brain polyamine metabolism, termed the polyamine-stress-response is a common response to stressful stimuli. Previous studies have implicated an over-reactive polyamine response as a component of the maladaptive brain response to stressful events, and as a novel molecular mechanism involved in the pathophysiology of affective disorders. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. Additionally, an important characteristic of affective disorders is their age dependency, a phenomenon that may be correlated with a maladaptive regulation of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system. In the present study we measured the activities of the enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase as markers of polyamine synthesis and found that unlike adults, immature rats do not show the characteristic brain polyamine-stress-response. Instead of the characteristic increase observed in adults, ornithine decarboxylase activity in immature animals was reduced or remained unchanged (for up to 16 days of age) after a dexamethasone injection or restraint stress application. The ontogenesis of this ornithine decarboxylase response was brain region-specific, indicating its dependence on the stage of neuronal maturation. Animals treated with dexamethasone at 7 days of age, showed increased behavioral reactivity in the open-field test as adults and an attenuated increase in ornithine decarboxylase activity after a re-challenge with dexamethasone at age 60 days. The results indicate that: (1) the brain polyamine-stress-response is developmentally regulated and its ontogenesis is brain region-specific, indicating dependence on the stage of neuronal maturation; (2) the switch to a mature polyamine-stress-response pattern coincides with the cessation of the stress hyporesponsive period in the HPA system: (3) activation of the polyamine-stress-response, as in the mature brain, appears to be a constructive reaction, while its down-regulation, as in the developing brain, may be implicated in neuronal cell death; (4) an attenuated dexamethasone-induced increase in ornithine decarboxylase activity implicates an altered polyamine-stress-response in the maladaptive response of the brain to stressful events.     

Enolase isoenzymes. III. Chromatographic and immunological characteristics of rat brain enolase

1. The chromatography of rat brain enolase (2-phospho-D-glycerate hydrolyase, EC 4.2.1.11) reveals three distinet components. One of these appears to be isoenzyme 1 (alpha alpha) but isoenzymes 2 (alpha beta) and 3 (beta beta) are absent. 2. The most acidic form of brain enolase was partially purified and an antiserum raised against it in the chicken. 3. a combination of chromatographic and immunological studies showed that a third type of subunit (gamma) is present in the brain giving rise to two further isoenzymes (alpha gamma and gamma gamma). 4. Developmental studies on the brain enzyme show an increase in total enolase activity from foetal life to maturity and a concurrent rise in the proportion of brain specific dimers. 5. It is therefore concluded that there are three genetic loci alpha, beta and gamma, coding for the enolase isoenzymes of rat tissues.     

Altered response to histamine in brain tumor vessels: the selective increase of regional cerebral blood flow in transplanted rat brain tumor

The authors studied the effect of intracarotid administration of histamine on the regional cerebral blood flow (rCBF) in transplanted rat C6 glioma by the hydrogen clearance method. Histamine infusion at doses of 1 and 10 micrograms/kg/min produced an increase of rCBF in the tumor (24.6% +/- 16.4%, p < 0.002, and 37.6% +/- 18.2%, p < 0.0001, respectively) and also in brain surrounding the tumor (26.8% +/- 16.2%, p < 0.002, and 34.9% +/- 9.2%, p < 0.0001, respectively) without any significant changes in the ipsilateral hemisphere. Intravenous administration of pyrilamine (H1 antagonist) and cimetidine (H2 antagonist) reduced blood flow responses to histamine; cimetidine was a more effective blocking agent than pyrilamine. Intracarotid infusion of histamine (1 and 10 micrograms/kg/min) with intravenous injection of Evans blue dye disclosed the selective extravasation of dye in the tumor and the brain surrounding the tumor. These results indicated that brain tumor vessels could respond to histamine differently than normal brain capillaries. The mechanism of selective response to histamine could be explained either by increased permeability or by altered characteristics of histamine receptors in the tumor vessels.     

Effects of histamine on rat isolated atria

The effects of histamine were studied in atria obtained from untreated and reserpine-pretreated rats. At high doses, histamine caused a positive chronotropic response that was not antagonized by either promethazine or cimetidine. In the presence of propranolol or in atria from reserpine-pretreated rats histamine caused an atropine-sensitive negative chronotropic response. Large doses of histamine also caused a positive inotropic response in left atria that were antagonized by the beta adrenoceptor antagonist propranolol. Reserpine pretreatment abolished the inotropic response of histamine in the rat heart. The results indicate that in large doses histamine causes an indirect stimulation of beta adrenoceptors (right and left atrium) by releasing endogenous noradrenaline and of muscarinic receptors (right atrium) by releasing acetylcholine.     

Long-term effects of portacaval anastomosis on the 5-hydroxytryptamine, histamine, and catecholamine neurotransmitter systems in rat brain

Portacaval anastomosis (PCA) in the rat is used as a model for portal systemic encephalopathy. Changes in the serotonergic, histaminergic, and catecholaminergic neurotransmitter systems are often found shortly after PCA. We have examined the long-term effects of PCA on the aminergic systems in brains of male Wistar rats, which 8 months previously had been subjected to PCA. Precursors, amines, and metabolites were assayed by HPLC. Eight months after PCA, the catecholamine levels were unchanged in all brain regions. In contrast, tryptophan was evenly increased throughout the brain. The accumulation of 5-hydroxytryptophan after decarboxylase inhibition (NSD-1015; 100 mg/kg i.p.) and the endogenous levels of 5-hydroxyindoleacetic acid were significantly higher in PCA rats, particularly in the hypothalamus and midbrain, whereas 5-hydroxytryptamine concentrations were unchanged. Histamine levels were elevated throughout the brain with the greatest increase found in the hypothalamus and in the striatum. tele-Methylhistamine levels were significantly elevated in cortex and hypothalamus. We conclude that 8 months after PCA, catecholaminergic systems had reestablished their homeostasis, whereas serotonergic and histaminergic systems still show profound disturbances in their function. With histamine, this is reflected as an increase in the amounts of both transmitter and metabolite; serotonergic neurons respond by increasing only the level of the metabolite.     

Developmental alterations in N-methyl-D-aspartate stimulated [3H]norepinephrine release in rat brain cortex and hippocampus

Developmental alterations in N-methyl-D-aspartate (NMDA)-stimulated[3H]norepinephrine release from rat brain cortical and hippocampal slices were studied. NMDA (10-1000 microM) resulted in a concentration-dependent increase in [3H]norepinephrine efflux; maximal responses (% released) in the cortex were: (1.53 +/- 0.12, 3.68 +/- 0.20, 2.94 +/- 0.20, 4.60 +/- 0.28 and 5.28 +/- 0.33) and the hippocampal responses were: (1.90 +/- 0.18, 3.84 +/- 0.23, 3.60 +/- 0.28, 5.16 +/- 0.38 and 5.81 +/- 0.45) at varying postnatal ages (1, 7, 14, 21 and 90 days) respectively. Cortical tissue from 7-day-old pups exhibited a transient increase in maximal efflux and a decrease in EC50. These results indicated that developmental alterations in the NMDA receptor appear to be translated into differences in NMDA stimulated [3H]norepinephrine release.     

Partial purification of protein farnesyl cysteine carboxyl methyltransferase from bovine brain

Asian upper and lower eyelids are typically characterized by a fuller appearance than the lids of whites. Inferior extension of preaponeurotic fat and brow fat into the Asian upper lid explain the upper lid fullness and its difference from the upper lid of whites. Analogous structures in the Asian lower lid may exist to explain its full appearance. High-resolution magnetic resonance imaging (MRI) of 24 normal Asian and white lower lids was performed to evaluate differences in Asian and white lower lid anatomy. Magnetic resonance images revealed two major differences. First, the orbital fat projected further anteriorly with respect to the orbital rim in all Asian lower lids studied. No analogy with the upper lid exists for this difference. Second, the orbital fat extended further superiorly, to the inferior border of tarsus, in those Asian lower lids that did not have well defined creases. This was analogous to the preaponeurotic fat location of the Asian upper lid and different from the white lower lid. The suborbicularis oculi fat in the lower lid, the analogous structure of the brow fat pad in the upper lid, was not different in location in Asian and white lower lids. Therefore, the Asian lower lid appearance is explained by the difference in orbital fat location, which is only partly analogous to the anatomical differences between the Asian and white upper lids.     

Developmental changes of tetrahydrobiopterin in rat and human erythrocytes

In the present study, we investigated the developmental changes of (1) plasma and erythrocyte tetrahydrobiopterin (BH4); (2) erythrocyte GTP cyclohydrolase (the rate-limiting enzyme of BH4 biosynthesis); (3) the permeability of erythrocyte membrane to BH4; and (4) plasma phenylalanine, both in healthy human subjects and Wistar rats. In vitro experiments demonstrated passive transport of BH4 into erythrocytes. In humans, BH4 levels as well as the other parameters were fairly consistent across all age groups. In contrast, Wistar rats showed significant developmental changes in erythrocyte BH4, which were not simply correlated to either GTP cyclohydrolase, permeability to BH4 or plasma phenylalanine levels. This may suggest the existence of other factors regulating the homeostasis of BH4, such as BH4-binding capacity in plasma and/or erythrocytes. These species/age differences in erythrocyte characteristics may influence the pharmacological behavior and clinical efficacy of BH4 in humans and experimental animals.     

Effect of adenosine metabolites on methyltransferase reactions in isolated rat livers

As introduction to a light- and electron-microscopial examination of rejected human corneal grafts a summary is given of the clinical signs of rejection. It is extremely important to recognize these signs in time and to initiate the correct therapy. Most failures in corneal transplantation are due to rejection. Rejection reactions are often not recognized early enough. The differential diagnosis is difficult because so many factors can trigger off a rejection. As the diagnosis is so often missed it is a good thing to consider the clinical picture of graft rejection once more. Maumenee: 'most ophthalmologists do not recognize the signs of early graft failure and usually do not refer the patient back for therapy until considerable oedema has developed from endothelial destruction' (1962). In the cases with a good prognosis the rejection percentage is plus or minus 12%; in vascularized corneas and complicated corneal transplantations as high as 75% (Polack, 1977).     

Repeated administration of opioids alters characteristics of membrane-bound phorbol ester binding in rat brain

Scatchard analysis of saturation binding data indicated that dissociation constant (KD) of [3H]phorbol 12,13-dibutyrate (PDB) binding to the membrane-bound protein kinase C of rat cortex and midbrain was significantly decreased following systemic repeated administration of morphine (mu-opioid receptor agonist) and butorphanol (mu/delta/kappa-mixed opioid receptor agonist). No change in the receptor density (Bmax) of [3H]PDB binding was found following repeated treatment with morphine and butorphanol. On the other hand, neither the Bmax nor KD values in pons/medulla were altered in these rats. These results suggest that systemic repeated opioid treatment, such as morphine and butorphanol leads to an increased affinity for phorbol ester binding to the membrane-bound protein kinase C in rat cortex and midbrain.     

Developmental science and the media: Early brain development.

Media coverage of early brain development not only has focused public attention on early childhood but also has contributed to misunderstanding of developmental neuroscience research. This article critically summarizes current research in developmental neuroscience that is pertinent to the central claims of media accounts of early brain development, including (a) scientific understanding of formative early experiences, (b) whether critical periods are typical for brain development, (c) brain development as a lifelong process, (d) biological hazards to early brain growth, and (e) strengths and limits of current technology in developmental brain research. Recommendations are offered for strengthening the constructive contributions of research scientists and their professional organizations to the accurate and timely coverage of scientific issues in the media. (PsycINFO Database Record (c) 2010 APA, all rights reserved)