bluuebunny/crossref_metadata_2025 huggingface dataset:
Insect prothoracicotropic hormone: a new member of the vertebrate growth factor superfamily
Authors: Noguti Tosiyuki , Adachi-Yamada Takashi , Katagiri Teruhiko , Kawakami Atsushi , Iwami Masafumi , Ishibashi Jun , Kataoka Hiroshi , Suzuki Akinori , Gō Mitiko , Ishizaki Hironori
Published: April 2003

Prothoracicotropic hormone (PTTH) is a brain neurosecretory protein that controls insect development. PTTH of the silkmoth Bombyx mori is a homodimeric protein, the subunit of which consists of 109 amino acids. Clear‐cut sequence similarity to any other proteins has not been observed. By disulfide‐bond pattern analysis and modeling of the PTTH structure based on the known three‐dimensional (3D) structures of growth factor family with cystine‐knot motif, we propose that the PTTH protomer adopts the fold unique to the structural superfamily of the growth factors, β‐nerve growth factor (β‐NGF), transforming growth factor‐β2 (TGF‐β2), and platelet‐derived growth factor‐BB (PDGF‐BB). The insect neurohormone PTTH appears to be a member of the growth factor superfamily, sharing a common ancestral gene with the three vertebrate growth factors, β‐NGF, TGF‐β2 and PDGF‐BB.
The 3D‐structure of a natural inhibitor of cell adhesion molecule expression
Authors: Hommel Ulrich , Weber Hans-Peter , Oberer Lukas , Ulrich Naegeli Hans , Oberhauser Berndt , Foster Carolyn A.
Published: April 2003

The three‐dimensional structure of cyclopeptolide HUN‐7293, a naturally‐occurring inhibitor of cell adhesion molecule expression, has been determined from nuclear magnetic resonance data recorded in solution and from X‐ray diffraction analysis of single crystals. The backbone conformation of HUN‐7293 is characterized by two cis‐peptide bonds in both the solution and crystalline state. Differences between the solution and crystal structure are visible for the orientation of some side chains and the strength of two transannular hydrogen bonds. Such structural information helps to provide insight into the molecular architecture of HUN‐7293 on the atomic level and opens the way for structure‐based modifications of this novel inhibitor of cell adhesion molecule expression.
The α2/δ subunit of voltage sensitive Ca2+ channels is a single transmembrane extracellular protein which is involved in regulated secretion
Authors: Wiser Ofer , Trus Michael , Tobi Dror , Halevi Sarah , Giladi Eli , Atlas Daphne
Published: April 2003

The membrane topology of α2/δ subunit was investigated utilizing electrophysiological functional assay and specific anti‐α2 antibodies. (a) cRNA encoding a deleted α2/δ subunit was coinjected with α1C subunit of the L‐type calcium channel into Xenopus oocytes. The truncated form, lacking the third putative TM domain (α2/δΔTMIII), failed to amplify the expressed inward currents, normally induced by α
1c coinjected with intact α2/δ subunit. Western blot analysis of α2/δΔTMIII shows the appearance of a degraded α2 protein and no expression of the full‐size two‐TM truncated‐protein. The improper processing of α2/δΔTMIII suggests that the α2/δ is a single TM domain protein and the TM region is positioned at the δ subunit. (b) External application of anti‐α2 antibodies, prepared for an epitope within the alternatively spliced and ‘intracellular’ region, inhibits depolarization induced secretion in PC12, further supporting an external location of the α2 subunit and establishing δ subunit as the only membrane anchor for the extracellular α2 subunit.
Neutrophils convert tyrosyl residues in albumin to chlorotyrosine
Authors: Kettle Anthony J.
Published: April 2003

Hypochlorous acid chlorinates tyrosyl residues in small peptides to produce chlorotyrosine. Detection of chlorotyrosine has the potential to unequivocally identify the contribution hypochlorous acid makes to inflammation. I have developed a selective and sensitive HPLC assay for measuring chlorotyrosine. When albumin was exposed to reagent hypochlorous acid, or that produced by myeloperoxidase and stimulated neutrophils, tyrosyl residues in the protein were converted to chlorotyrosine. About 2% of the hypochlorous acid generated by neutrophils was accounted for by the formation of chlorotyrosine. These results demonstrate that chlorotyrosine will be a useful marker for establishing a role for hypochlorous acid in host defence and inflammation.
Acidic phospholipids inhibit the phospholipase D activity of rat brain neuronal nuclei
Authors: Kanfer J.N. , McCartney D.G. , Singh I.N. , Freysz L.
Published: April 2003

An oleate dependent form of phospholipase D is present in rat brain neuronal nuclei and both the hydrolytic and transphosphatidylation activities measured. Several acidic phospholipids were found to inhibit this activity in a dose dependent manner. The IC50 values varied from 3.5 μM for PIP2 to 200 μM for phosphatidic acid. The hydrolysis of PIP2 by phospholipase C would be expected to result in the disinhibition of the oleate dependent phospholipase D activity.
Potato yellow mosaic geminivirus AC2 protein is a sequence non‐specific DNA binding protein
Authors: Sung Y.K. , Coutts R.H.A.
Published: April 2003

The AC2 protein of potato yellow mosaic geminivirus (PYMV) is by analogy with related geminiviruses thought to be a transcriptional activator protein. We have over‐expressed the AC2 open reading frame in E. coli and purified the protein from bacterial extracts to near homogeneity. We have studied the interaction of the AC2 protein with DNA and from gel retardation assays shown that it binds both double‐stranded (ds) and single‐stranded (ss) DNA non‐specifically. The binding to PYMV intergenic region ds DNA appeared to be independent of the presence of zinc ions and did not require the protein to be phosphorylated.
Dual role of tropomyosin on chemically modified actin filaments from skeletal muscle
Authors: Hajime Honda  , Yoshiko Kitano  , Kuniyuki Hatori  , Koichiro Matsuno
Published: April 2003

Actin filaments copolymerized with both intact and chemically modified actin monomers restored their sliding activity when they were supplemented with tropomyosin extracted from skeletal muscle. In contrast, the ATPase activation of the copolymers was decreased when supplemented with tropomyosin. The results indicate that tropomyosin along with actin monomers may facilitate sliding activity of the entire actin filament but suppress ATPase activation of intact actin monomers themselves. Accordingly, tropomyosin molecules could be viewed as playing a dual role of both mechanical and chemical regulation of actin monomers.
Influence of substrate structure on cleavage by hammerhead ribozyme
Authors: Scarabino Daniela , Tocchini-Valentini Glauco P.
Published: April 2003

We compared the cleavage by a hammerhead ribozyme of a wild‐type precursor tRNA (pre‐tRNA3
leu) and a structurally altered mutant form. We also analyzed the cleavage reactions of these tRNAs catalyzed by a ribozyme variant that was designed to complement the mutant precursor tRNA. Kinetic analyses reveal that the k
cat values are nearly the same for the wild‐type and the mutant substrate RNAs. However, the K
m values differ considerably, being higher for the wild‐type substrate. Thus, the formation of the ribozyme‐substrate complex, but not the chemical cleavage step, is affected by these changes. Time course studies were performed, at different temperatures, to estimate the efficiency of the cleavage reactions and the effect of temperature. The cleavage of mutant precursor tRNA is generally faster than the wild‐type at all temperatures analyzed. These results suggest that substrate structures can limit ribozyme efficiency, presumably by hindering the hybridization step.
A new EcoRI family of satellite DNA in lampreys
Authors: Boán Francisco , Viñas Ana , Rodríguez Jose Manuel , Sánchez Laura , Gómez-Márquez Jaime
Published: April 2003

Satellite DNA sequences have been studied in several groups of organisms. However, until now this type of sequence has not been characterized in cyclostomata, an evolutionarily important class of vertebrates. In the present work, we report the molecular characterization of a new family of satellite DNA in lampreys (Petromyzon marinus). Digestion of lamprey DNA with EcoRI identified a series of very abundant AT‐rich (60% A+T) repeating units, with short stretches of AT, that are multimers of 370 bp. Southern blot analysis and comparison with the satellite DNA sequences deposited in the databases indicate that this new family of satellite DNA is exclusive to lampreys. The distribution of this EcoRI satellite DNA on lamprey chromosomes was analyzed by in situ hybridization. The evolutionary origin of this satellite is briefly discussed.
Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells
Authors: Ida Nobuo , Masters Colin L. , Beyreuther Konrad
Published: April 2003

Cerebral deposition of βA4 (β‐amyloid) peptide is a major pathological feature of Alzheimer's disease. Although the mechanism of βA4 production from cells has been investigated extensively, so far little is known about the catabolism of the peptide. We report here that the human neuroblastoma cell line SH‐SY5Y can rapidly clear βA4 in the culture medium. The clearance was not due to the degradation by extracellularly released protease, but rather due to intracellular degradation after cellular uptake. This clearance activity was specific to SH‐SY5Y cells among several cell types examined. Some of the βA4‐derived peptides lacking the N‐terminal part of the molecule were not catabolized, suggesting a specific interaction between the cells and βA4. Although most of the peptide was degraded after uptake, small amounts of peptide was accumulated in insoluble fractions of the cells and remained stable for several days. These observations suggest that this uptake‐degradation activity may contribute to AD pathogenesis in two different ways: either to prevent the amyloid deposition by reducing extracellular βA4 concentrations, or to promote the deposition by producing insoluble seeds for amyloid formation.
A simple ligation assay to detect effects of drugs on the curvature/flexibility of DNA
Authors: Bailly Christian , Minnock Andrew , Waring Michael J.
Published: April 2003

Circular DNA molecules can readily be formed from the 169 bp tyrT fragment in the presence of T4 DNA ligase. We have analyzed the formation of DNA circles in the presence of the clinically important antitumour drugs amsacrine, mitoxantrone and daunomycin. All three are intercalating agents but they affect the closure reaction differently: daunomycin and mitoxantrone progressively inhibit the formation of circles whereas at low concentrations amsacrine strongly enhances the yield of circles suggesting that this drug can increase the flexibility and/ or curvature of DNA. The ligation assay described here may prove useful and widely applicable for investigating the effects of small molecules on the secondary structure of DNA.
Isolation and characterisation of a cDNA encoding rat mitochondrial GrpE, a stress‐inducible nucleotide‐exchange factor of ubiquitous appearance in mammalian organs
Authors: Naylor Dean J. , Hoogenraad Nicholas J. , Høj Peter B.
Published: April 2003

In contrast to the E. coli chaperones DnaK, GroEL and GroES, cDNAs encoding mitochondrial homologues of DnaJ and GrpE from higher eukaryotes have yet to be reported. Based on peptide sequences, we have isolated a cDNA encoding a 217 residue nuclear encoded precursor of rat mitochondrial GrpE (mt‐GrpE) including a typical mitochondrial presequence of 27 residues. Western blotting revealed that the 21 kDa GrpE homologue is present exclusively in the mitochondrial fraction where it comprises only ∼0.03% of the total soluble protein, while Northern blotting showed that the mt‐GrpE transcript is present in most if not all organs. By contrast to other mitochondrial chaperones, the levels of mt‐GrpE and its transcript in cultured cells are only marginally increased in response to the proline analog l‐azetidine 2‐carboxylic acid but not by heat shock. Furthermore, members of the GrpE family exhibit a much lower degree of sequence identity than do the well studied members of the Hsp70, Hsp60 and Hsp10 families.
Inhibition of ICE‐family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor‐induced apoptosis
Authors: Mirzoeva Olga K. , Yaqoob Parveen , Knox Kirstine A. , Calder Philip C.
Published: April 2003

Two lipophilic derivatives of caffeic acid which inhibit lipoxygenase, caffeic acid phenethyl ester (CAPE) and N,N′‐dicyclohexyl‐O‐(3,4‐dihydroxycinnamoyl)‐isourea (DCHCU), reduced the proliferative response of murine splenocytes to concanavalin A in vitro. Both CAPE and DCHCU induced apoptosis in murine thymocyte cultures as verified by flow cytometry and by visualisation of DNA with acridine orange staining. CAPE‐induced apoptosis was inhibited by z‐VAD‐fmk, an inhibitor of the interleukin‐1β‐converting enzyme family of cysteine proteases. We suggest that the lipoxygenase pathway of arachidonic acid metabolism plays a role in regulating lymphocyte responses such as proliferation and apoptosis.
Widespread expression of beta‐defensin hBD‐1 in human secretory glands and epithelial cells
Authors: Zhao Chengquan , Wang Ingrid , Lehrer Robert I.
Published: April 2003

We compared the expression of human α‐ and β‐defensins by various human tissues. mRNA for α‐defensins HNP1‐3, abundant in bone marrow, was detected in peripheral blood leukocytes, spleen and thymus by RT‐PCR, which revealed α‐defensins HD5 and HD6 only in the small intestine. In contrast, the pancreas and kidney expressed high levels of hBD‐1 and lower levels of this β‐defensin were found in many organs by RT‐PCR (salivary gland > trachea > prostate and placenta > thymus, testis, small intestine). hBD‐1 mRNA was produced constitutively by cultured normal human epithelial cells derived from the trachea, bronchi, small airways and the mammary gland. These largely non‐overlapping tissue distributions of human α‐ and β‐defensins suggest that hBD‐1 may be positioned to defend epithelial cells and mucosae from infection, whereas expression of HNP1‐3 in neutrophils and HD5 and HD6 in Paneth cells allows these α‐defensins to participate in systemic and small intestinal host defenses, respectively.
Transferrin in fetal rat brain and cerebrospinal fluid
Authors: New H. , Dziegielewska K. M. , Saunders N. R.
Published: April 2003

Concentrations of transferrin in plasma, cerebrospinal fluid (csf) and brain of fetal and newborn rats have been estimated by radial immunodiffusion assay. Transferrin was detected in both csf and brain at the earliest age investigated (12 days gestation). The plasma concentration increased throughout the gestational period studied and in the postnatal period: the overall increase was about 10‐fold. In contrast, although the csf transferrin concentration increased by 3 times between 12 and 22 days (term) there was a considerable decline on reaching adult age. Brain transferrin concentration was highest at 18 days gestation. These results are important background information for studies of the significance of transferrin in brain development.
Conditioned medium from spinal cord cells stimulates DRG cells to migrate, cluster and rearrange in dissociated cell cultures
Authors: Klotz Kathleen L. , Neale Joseph H.
Published: April 2003

Murine spinal sensory neurons migrate in dissociated cell culture resulting in convergence, divergence and cluster rearrangement by the cells. We found that culture medium which had been conditioned by the growth of spinal cord cells stimulated the convergence of DRG cells into clusters. Binuclear sensory neurons, which are often found in these cultures, failed to migrate or proceed with mitotic cleavage during the 2 weeks of observation. We conclude that these cells were arrested in mitosis during or shortly after their removal from the 13‐day‐old embryo.
Biochemical compensation and recovery following temporary inhibition of ornithine decarboxylase during the development of rat cerebellar cortex
Authors: Gilad Gad M. , Carstairs Jill , Gilad Varda H.
Published: April 2003

Specific inhibition of ornithine decarboxylase selectively in the developing rat cerebellum was achieved within 10 min after intrathecal injection of α‐difluoromethylornithine. Twelve hours later the activity started to increase, passed control levels between 2 and 3 days, continued to increase and reached its peak values by day 3 (when animals were 10 days old), 3 days after peak control values. Ornithine decarboxylase activity then declined and attained low adult values simultaneously with controls. Glutamic acid decarboxylase activity, a marker of gabaergic neurons maturation, declined to a nadir at 3 days postinjection, and then was elevated transiently above control levels with a peak at 11 days postinjection. We conclude that after such a temporary insult neuroblasts of the cerebellar cortex are capable of full recovery, which is apparent by a reversible reduction in ornithine decarboxylase and glutamic acid decarboxylase activities followed by a transient compensatory elevation in both enzymes.
Neonatal hypothyroidism and early undernutrition affect myelin and myelin precursor membranes in a different way
Authors: Pasquini J.M. , Bizzozero O. , Sato C. , Oteiza P. , Soto E.F.
Published: April 2003

The lipid and protein composition as well as the activity of 2′3′ cyclic nucleotide 3′ phosphohydrolase (CNPH) and the distribution of individual proteins separated by SDS‐PAGE were studied in myelin and in a fraction closely related to myelin or assumed to be a precursor membrane of mature myelin (fraction SN4) isolated from 20‐day‐old rats made hypothyroid at birth or submitted to early malnutrition.

In both experimental conditions lipid and protein components were found to be reduced in myelin when data were expressed as mg/g fresh tissue, but the results were close to those obtained in normal controls when data were expressed as mg/mg total protein of each fraction. CNPH activity was normal in myelin but markedly reduced in fraction SN4. Although the results appear to suggest that both experimental conditions produce a reduction in the amount of myelin but no qualitative changes, the data obtained with SDS‐PAGE show that the distribution of the various types of proteins present in this fraction and fraction SN4 was abnormal. Myelin and fraction SN4 isolated from malnourished animals displayed a protein profile which was quite similar to that found in fraction SN4 isolated from normal rats, indicating a delay in the process of myelin maturation. The changes in protein composition of myelin and fraction SN4 produced by neonatal hypothyroidism on the other hand differed clearly from those produced by early malnutrition; the ratio small basic protein: large basic protein (SBP:LBP) was found to be reduced in both membrane fractions in the former condition and the protein patterns of myelin and that of fraction SN4 were different, at variance with what was found in the case of malnourished animals.

Our findings appear to suggest that the effects of early malnutrition and neonatal hypothyroidism upon myelin and myelin‐related membranes are different, and that myelination is more affected in the latter condition.
Critical periods for the role of ornithine decarboxylase and the polyamines in growth and development of the rat: Effects of exposure to α‐difluoromethylornithine during discrete prenatal or postnatal intervals
Authors: Slotkin T.A. , Seidler F.J. , Whitmore W.L. , Weigel S.J. , Slepetis R.J. , Lerea L. , Trepanier P.A. , Bartolome J.
Published: April 2003

The roles of ornithine decarboxylase (ODC) and the polyamines in fetal and neonatal development were examined through the use of α‐difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC. Administration to pregnant rats of 500 mg/kg of DFMO every 12 h for a 4‐day period (8 DFMO injections) resulted in fetal and neonatal death; DFMO early in gestation produced fetal resorption whereas late gestational exposure did not compromise fetal viability but instead resulted in a delayed toxic effect, with high mortality in the first postnatal week. Generalized toxicity of DFMO was not apparent in later developmental periods, as 4 days of DFMO treatment begun postnatally did not produce any neonatal death. Shortening the course of gestational DFMO treatment to 2.5 days (5 DFMO injections) also did not adversely affect fetal or neonatal viability and thus permitted identification of critical periods in which various tissues are sensitive to DFMO. Examination of growth patterns of brain, heart and kidney and of neurochemical development of central and peripheral catecholaminergic neurons indicated that different critical periods exist for effects of DFMO on each tissue or even on the various cell types within a tissue. The separable sensitivities were apparent even though the effects of DFMO on ODC and the polyamines for any given treatment period were fairly uniform in all tissues studied. These results indicate that the ODC/polyamine system plays multiple roles in fetal survival and in tissue growth during discrete periods of development; because the time course of cellular maturation differs for each tissue or cell population, DFMO administered during any one brief period can produce organ‐specific developmental deficits.
Opiate binding to brain slices and ontogenesis of hypothalamic [3H]naloxone binding sites
Authors: Bhanot R. , Wilkinson M.
Published: April 2003

We have developed a radioligand binding assay based on the use of hypothalamic slices and have examined the ontogenesis of [3H]naloxone binding sites in male and female rats. [3H]NAL binding is reversible, saturable, stereospecific, of high affinity, readily displaceable by morphine and is sensitive to phenoxybenzamine. These characteristics suggest that [3H]NAL readily binds to opiate receptors in brain slices. With this assay we have demonstrated that: (a) there is an age‐related increase in opiate binding sites in rat hypothalamus, (b) there are sex differences in the binding affinity of the sites and (c) the values of Bmax are approximately 2–5‐fold higher than the levels previously reported from assays with brain homogenates.
Effects of neonatal capsaicin treatment on thiamine monophosphatase (TMPase) activity in the substantia gelatinosa of the rat spinal cord
Authors: Inomata Kenichirou , Nasu Fumio
Published: April 2003

The present study investigated changes in gelatinosal TMPase activity following capsaicin treatment. The gelatinosal TMPase activity was positive around postnatal day 3, and the activity disappeared when newborn rats were treated with capsaicin on postnatal days 2 or 3. The absence of TMPase activity was still observed four months after treatment. The possibility that TMPase is associated with nociception has to be considered.
Fine structure of the cells containing large granular vesicles in the superior cervical ganglia of rat embryos
Authors: Soinila S. , Eränkö O.
Published: April 2003

An electron microscopic study has been performed on the superior cervical ganglia of 11‐ to 21‐day‐old rat embryos after fixation with glutaraldehyde and osmium tetroxide. The ganglia of 11‐day‐old and older embryos are known to consist of cells which show catecholamine fluorescence, the intensity of which varies from weak to bright. Electron microscopically, the ganglia of 11‐ and 12‐day‐old embryos were observed to consist of a dense group of cells among the loose mesenchyme. The cells showed a great variation in nuclear morphology and only rarely contained granular vesicles. Only few cells represented the undifferentiated, primitive sympathetic cell type described in previous studies. Therefore, in the rat superior cervical ganglion the ultrastuctural differentiation may be initiated even before the cells complete their migration.

From embryonic day 14, three types of cell containing varying numbers of large granular vesicles were distinguished on the basis of nuclear morphology. Those type 1 cells that contained numerous granular vesicles closely resemble the postnatal SIF cells. Those type 2 cells that possessed a great number of granular vesicles may represent an intermediate form, namely the large intensely fluorescent cell described in prenatal ganglia but only exceptionally found in early postnatal ganglia. The appearance of the type 2 cells with only a few granular vesicles is identical with that of the sympathetic cells representing the early stages of maturation. The type 3 cells correspond with the late maturing principal neuron. These cells were never seen to contain more than a few large granular vesicles.
The effect of cortisol on gamma‐glutamyl transpeptidase activity in the glycogen body and lumbosacral segments of developing chick spinal cord
Authors: Šťastný F. , Lisý V. , Sedláček J. , Hájková B.
Published: April 2003

Gamma‐glutamyl transpeptidase (GGT) activity is heterogeneously distributed between the lumbosacral chick spinal cord and the adjacent glycogen body during late embryonic and early posthatch development and displays hormonal sensitivity. As GGT activity may reflect the cellular transport of some amino acids, the transiently high activity of this enzyme in the glycogen body suggests that these cells play an important role in amino acid transport and metabolism at a time coincident with the initial phase of myelination in the embryonic chick spinal cord.
Delayed development of GFA immunoreactivity in intraocular cortex cerebri grafts during thyroid hormone deficiency
Authors: Granholm Ann‐Charlotte , Dahl Doris , Björklund Håkan , Seiger Åke
Published: April 2003

Dependency of astrocytes on thyroid hormones during development was studied in intraocular cortex cerebri grafts, using antibodies to the glial fibrillary acidic protein (GFA). Fetal cortex cerebri was left in the anterior eye chamber of normal and thyroidectomized adult recipient rats 3 and 8 weeks to mature. All cortex grafts survived and became vascularized in the eye. The grafts were cryostat‐sectioned, and reacted with an antiserum specific for GFA. The density of GFA immunoreactivity in the cortex graft neuropil was subjectively estimated with fluorescence microscopy. After 3 weeks in oculo, the number of positive structures was significantly lower in the thyroidectomized group as compared to the euthyroid control group. This effect of thyroidectomy on the cortex grafts was entirely counteracted by daily injections of thyroxine (100 μg/kg s.c.) to similarly thyroidectomized recipients. The distribution of GFA‐positive structures was even within individual grafts of all three groups. Neither were any differences in morphology of fluorescent astroglial processes observed. The overall density of fluorescent GFA‐positive structures was considerably higher than that found in age‐matched normal in situ counterparts, even in the thyroidectomized group. After 8 weeks in oculo, the difference between the control and thyroidectomized groups in density of GFA‐positive structures in the neuropil had disappeared, and no general increase in density of immunoreactivity was noted in the control group. These results indicate that thyroid hormones might normally play a role for the development of GFA in the early postnatal brain, as thyroid hormone deficiency causes a transient delay in development of GFA immunoreactivity in intraocular cortex cerebri grafts.
The effects of apomorphine and isoproterenol on the ‘transport response’ in the white rat
Authors: Wilson Christopher
Published: April 2003

In a series of four experiments, the ability of specific catecholaminergic agonists to intensify the ‘transport response’ was investigated in 19‐, 32‐, 36‐ and 40‐day‐old rats. The dopaminergic agonist, apomorphine, was able to intensify the response in a dose‐dependent fashion. The beta‐noradrenergic agonist, isoproterenol, was unable to alter the intensity of the response. These results indicate a central dopaminergic involvement in the transport response.
Interplexiform, horizontal and bipolar‐like cells of the rabbit retina take up exogenous serotonin during early developmental stages
Authors: Osborne N.N.
Published: April 2003

A subpopulation of amacrine cells which have the ability to take up exogenous serotonin occur in the rabbit retina at all stages during postnatal development. However, during the initial stages of the retina's development some serotonin‐accumulating neurons are also associated with the outer plexiform layer in the form of interplexiform and/or bipolar and/or horizontal cells. These neurons could have an additional function of their own or simply be misplaced serotonin‐accumulating neurons destined to degenerate in the process of synaptogenesis.
Increase in the number and volume of myenteric neurons in the adult rat
Authors: Robecchi Maria G. Giacobini , Cannas Mario , Filogamo Guido
Published: April 2003

In response to enhanced functional activity, only the larger neurons of the myenteric plexus incorporate thymidine. Their number, too, is increased. This phenomenon is not accompanied by proliferation.
Neural transplantation: Autoradiographic analysis of histogenesis in neocortical transplants
Authors: Das Gopal D. , Ross Douglas T.
Published: April 2003

Ncurohistogenesis in neoeortical transplants obtained from 15‐, 16‐. 17‐, 18‐, 19‐, 20‐ and 21 day‐old embryos, was studied employing [3H]thymidine autoradiography. The neural tissues were transplanted in the midvcrmis of cerebellum of the host animals. Following transplantation the host animals in different groups were injected with the radiochemical at 6 hr. 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 day intervals, to label the neurons forming on different days in the developing transplants. Analysis of auto radiograms showed that all the neoeortical transplants did undergo histogenesis in the host cerebellum and that it was similar to that seen in a normally developing neocortex. Transplants from the 15‐day embryos showed histogenesis lasting for 9 days and at the other extreme transplants from the 21‐day embryos showed histogenesis lasting only for 1 day. Histogenesis in other transplants fell between these two extremes in a graded fashion in relation to the age of the donor embryos. The magnitude of histogenesis in transplants from different donor embryos was closely related to the final size of the transplants. Transplants from 15‐day embryos were the largest in size and they were followed by those from 16‐, 17‐, 18‐, 19‐, 20‐ and 21‐day donor embryos in a graded fashion. All transplants were intraparenchymal and histologically appeared normal. They contained fully differentiated neurons and were anatomically integrated with the host cerebellum without any glial scar tissue or necrotic tissue intervening between them.
Long‐term consequence of early iron‐deficiency on dopaminergic neurotransmission in rats
Authors: Ben‐Shachar Dorit , Ashkenazi Ruth , Youdim Moussa B.H.
Published: April 2003

Nutritional iron‐deficiency (ID) induced in rats caused a reduction in peripheral as well as central iron metabolism. This effect was markedly greater in the liver than the brain. Although the decrease in the rate of brain non‐haem iron was slower than that of serum and liver, significant diminutions of behavioral response to apomorphine (2 mg/kg) and maximum [3H]spiperone binding (Bmax) in caudate nucleus were noted in these animals. These effects of ID can be reserved byron supplementation in young (21‐day‐old) and adult (48‐day‐old) rats. In contrast, if ID is induced in new born (10‐day‐old) animals, the diminished brain non‐haem iron, behavioral response to apomorphine and [3H]‐spiperone binding in caudate nucleus will not recover even after 6 weeks of iron supplementation. However, these animals have normal serum iron, haemoglobin and liver iron. These data point to the profound effect early ID can have on the development of dopaminergic neurotransmission, since brain iron concentration increases its maximum in the 4–5 weeks after birth. The implications of the present finding is that the prevalence of ID in children occurs in the first decade of life, when brain iron accumulation reaches values observed in adults. The profound cognitive changes associated with ID in children is thought to be dopamine‐dependent and is not always reversible with iron therapy.
Cytotoxic effects of monodansylcadaverine and methylamine in primary cultures of rat cerebellar neurons
Authors: Gilad Gad M. , Gilad Varda H.
Published: April 2003

The effects of dansylcadaverine and methylamine, competitive inhibitors of transglutaminase. were examined in primary cultures of dissociated rat cerebellar neurons. Addition of the drugs at plating time resulted 24 hr later in irreversible cytotoxic effects evidenced by failure of aggregation and neurite formation. Cytotoxicity was dose‐dependent with methylamine being more potent (1C50 = 20μm) than dansylcadaverine (IC50 = 30μM). The cytotoxic effects were less potent when drugs were added 24 hr after plating, the time when neurons had already begun to extend neurites. Drugs were effective in the various sera and heat‐inactivated sera tested. We concluded that low doses of methylamine and dansylcadaverine have potent toxic effects on primary neuronal cultures.
Are the effects of gestational stress on motor development and cerebellar cholinesterase activity mediated prenatally?
Authors: Fride Ester , Soreq Hermona , Weinstock Marta
Published: April 2003

Prenatal random noise and light stress retards early motor development in the rat. To determine whether this delay is pre‐ or postnatally mediated and whether the developing cerebellum may play a role in the delay, rats were subjected to this form of stress and their offspring were fostered or cross‐fostered onto control rats and vice versa. Their motor development was assessed by a series of behavioral tests between birth and day 10 of life.

Prenatally stressed pups (Eo). whether reared by stressed (Em) or control mothers (Cm), showed a retardation in motor development. However, stressed pups matured earlier when reared by a control mother than by a stressed dam. Control pups (Co) raised by stressed mothers showed normal behavioral development.

Cerebellar cholinesterase activity, which has been shown to undergo characteristic alterations with normal maturation, did not differ between stressed and control pups at birth. However, on day 10, cholinesterase activity was lower in EmCo than in CmCo pups, whereas that in CmEo and EmEo pups did not differ significantly from controls.

It is concluded that three effects of random noise and light stress during pregnancy may be distinguished: (1) A prenatal effect as expressed by a delay in motor development, (2) a postnatal (rearing) effect on motor development and (3) a rearing effect expressed as a decrease in cerebellar ChE activity.
Early olfactory deprivation and the mitral cells of the olfactory bulb: A Golgi study
Authors: Meisami Esmail , Noushinfar Elaheh
Published: April 2003

Golgi impregnation was used to study the morphology, morphometry and number of mitral cells in control and stimulus‐deprived olfactory bulbs (OB) of 25‐day‐old albino rats. The rats were made unilaterally anosmic by closure of one nostril in the early neonatal period. The previously described reductions in the size of OB and thickness of OB layers were confirmed. Quantitative comparison of the control and anosmic OB revealed that in the odor deprived OB the number of Golgi impregnated mitral cells was 40% less and the impregnation of dendritic neuropil in the external plexiform layer was greatly reduced. Of the remaining mitral cells of the odor‐deprived OB, a small portion exhibited an ‘atrophic’ appearance with markedly reduced impregnation of the intracellular material, while the majority showed relatively ‘normal’ morphology. Morphometric measurements and statistical comparison of the means revealed that in the remaining ‘normal’ mitral cells, there were significant reductions in the following parameters: (1) the size of the cell soma as measured by the vertical and transverse diameters (17 and 12%); (2) length of the apical dendrite (27%); (3) diameter of the glomerular tuft (22%); (4) total length of the basal dendrites (18%); (5) diameter of the dendritic field of the basal dendrites (22%). The pattern of impregnation did not differ between the control OB of the experimental rats and the normal OB of normal rats. The results indicate that an absence of olfactory stimulation during the postnatal period exerts deleterious transneuronal influences on the developing mitral neurons, leading to atrophy and loss for some and diminished somatic and dendritic growth for others.
Ocular changes in the mouse embryo following acute maternal ethanol intoxication
Authors: Kennedy L. A. , Elliott M. J.
Published: April 2003

The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 μm2 in the neural layer of the retina compared to controls, but there was an alcohol‐related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7‐fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcoholrelated reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.
Astroglial development in microencephalic rat brain after fetal methylazoxymethanol treatment
Authors: Eriksdotter‐Nilsson M. , Jonsson G. , Dahl D. , Björklund H.
Published: April 2003

Treatment of pregnant rats on gestation day 15 with methylazoxymethanol (MAM) leads to a marked microencephaly in the offspring with a considerable atrophy in cerebral cortex, hippocampus and striatum. The development of the astrocytic populations in these atrophic regions was studied by means of immunohistochemistry using an antiserum against glial fibrillary acidic protein (GFA). The distribution and density of GFA‐positive structures were not notably altered in the parietal cortex, hippocampal formation and striatum after prenatal MAM‐treatment as compared to control. Also the individual astrocytes were morphologically similar in experimental and control animals in all regions analyzed. We suggest that an adjustment of the astrocytic development has occurred in response to the changed neuronal environment. Alternatively, MAM‐treatment may affect neuronal and glial precursor cells leading to a seemingly normal astrocytic cell density.
Acquisition of acoustic startle shows a dose‐response to serum free T4
Authors: Schneider Bernard F. , Golden Wendy L.
Published: April 2003

Methimazole, administered to rats in drinking water (0.1 and 0.05%) from embryonic day 17 to postnatal day 10, caused a dose‐dependent decrease in serum Free T4 and an accompanying dose‐dependent delay in acquisition of acoustic startle reflex. In conjunction with other studies showing the specific dependence of acoustic startle development on thyroid hormone, this study suggests that the acoustic startle system may be a useful model for determining thyroid hormone requirements for normal neurologic development.
Alterations in gastric acid secretion following hepatic vagotomy at a stage of development in rats
Authors: Ohtake Masahiro , Sakaguchi Takeo
Published: April 2003

The relation of gastric acid secretion to the hepatic vagal section was examined in consideration of developmental stages of a rat. Acid outputs in rats deprived of food for 22 hr before the experiment were estimated with or without insulin. The animals were classified into five groups according to their body weights at the experiments (50, 100, 200, 300 and 400 g). Hepatic vagotomy was effective in decreasing acid output in all of the groups treated with food deprivation and insulin, and it was found that there was a close relationship between the output and glucose concentration in the portal blood. In rats treated only with food deprivation, hepatic vagotomy produced different effects for the five groups; the vagotomy failed to cause acid response when the rats weighed about 300 and 400 g, while in the animals weighing about 50, 100 and 200 g acid outputs were reduced following the vagotomy. It was noted that the sensitivity to hypoglycemia in the acid output was greater in the young rats than the older ones. Results suggest that function of the hepatic vagal nerve may be prominent in modulating acid secretion in an earlier stage of development when the animals are most sensitive to hypoglycemia.
Normal zinc and iron concentrations in mice after early exposure to phenobarbital
Authors: Pick Chaim G. , Statter Marian , Shachar Dorit Ben , Youdim Moussa B. H. , Yanai Joseph
Published: April 2003

Zinc and iron levels were studied in mice with early (pre/neonatal) exposure to phenobarbital, as the levels of these trace metals are known to be correlated with specific behaviors shown in our previous and present experiment to be affected by early phenobarbital administration. Mice were exposed to phenobarbital prenatally or neonatally. At adulthood they showed marked reduction from control in all parameters of eight‐arm maze performance (P < 0.001). Since zinc is known to be correlated with this behavior, it was subsequently studied in barbiturate exposed animals. The differences between barbiturate exposed and control offspring for zinc levels in plasma, brain and hippocampus did not reach statistical significance. Our previous studies have shown that the number of dopamine receptors and the resulting apomorphine‐induced climbing behavior is altered after early exposure to phenobarbital. The effect of iron level on dopamine receptors is now well established. Subsequently, a group of mice were tested for iron levels in their brain and liver. No significant differences were found.

It is suggested that deficits in the hippocampal behaviors, mainly eight‐arm maze, after early exposure to phenobarbital are not related to changes in zinc levels. Similarly, early phenobarbital‐induced alternation in dopamine receptors and the resulting dopaminergic behaviors are not related to changes in iron levels.
Effects of nerve growth factor on autonomic neurons in the chick embryo: A stereological study
Authors: Dimberg Yvonne , Ebendal Ted
Published: April 2003

Quantitative effects of nerve growth factor (NGF) on the sympathetic, Remak and ciliary ganglia in chicken embryos were investigated. Purified mouse βNGF was injected (80 μg per day for three or four consecutive days) into the yolk sac at different stages (starting on days 6, 8, 10 and 13) of embryonic development. Ganglia were taken for fixation and embedding one day after the last NGF injection. The number of neurons belonging to the different size classes was determined by a computer aided stereological method based on unfolding of cell diameter frequencies. The volume of sympathetic ganglia was increased at all stages with a maximum of 8‐fold occurring on day 10. The ganglion of Remak showed a 3‐fold volume increase up to embryonic days 10 and 12. Ciliary ganglia did not exhibit any differences in volume or neuron size between the controls and the embryos injected with NGF. The number of neurons was increased in younger sympathetic and Remak ganglia in response to NGF, as was the recruitment of neurons to the larger size classes.
Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics
Authors: McBride William G. , Hicks L. J.
Published: April 2003

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Ceasarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals.

Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 μg/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta.

The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations. However, it appears that thalidomide does not produce malformations through a change in acetylcholine levels in the fetus.
Role of glial cells in the differentiation and function of myelinated axons
Authors: Rosenbluth Jack
Published: April 2003

Myelinated axons are highly differentiated in the vicinity of the node of Ranvier, both structurally and with respect to ion channel distribution. Evidence is reviewed showing that axonal differentiation depends upon two distinct types of interaction between glial cells and the axolemma, one at the node itself, with astrocyte processes, and the second, more extensive one, in the paranodal region, with oligodendrocyte processes. In the peripheral nervous system, Schwann cells fulfill both roles. Glial or Schwann cell abnormalities, due to genetic deficiencies, diseases or experimental procedures, result in corresponding abnormalities in the axolemma and can have devastating effects on nerve fiber function. An example, the myelin‐deficient mutant rat, is presented, and the defects underlying the profound and ultimately lethal neurological abnormalities seen in this mutant are discussed in relation to abnormalities in its axoglial interactions.