Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo

Fumagillin is a naturally secreted antibiotic of the fungus Aspergillus fumigatus. It is used in veterinary medicine against microsporidiosis of bees and fish. In this study, the genotoxicity of fumagillin (in the form of fumagillin dicyclohexylamine) was evaluated in mouse bone-marrow cells using the mitotic index (MI), the chromosome aberration (CA) assay, and the micronucleus (MN) test. Fumagillin was administered to BALB/c mice by gavage, at doses of 25, 50, 75 mg/kg body weight (bw), repeated for 7 days at 24-h intervals, with water-sugar syrup as a negative control and cyclophosphamide (40 mg/kg bw) as a positive control. All experimental doses of fumagillin induced a significant decrease (p<0.001) in MI (3.47+/-0.04%, 3.17+/-0.01%, and 2.27+/-0.02%, respectively) in comparison with the negative control (6.00+/-0.01%). Fumagillin significantly (p<0.001) increased the frequency of MN (4.98+/-0.35, 8.45+/-0.57, and 12.02+/-0.37, respectively) over negative control (1.04+/-0.28). Significantly increased frequencies (p<0.01 or p<0.001) of numerical chromosomal aberrations (aneuploidies and polyploidies) and structural chromosomal aberrations such as gaps, breaks, and centric rings were observed at the highest experimental dose of fumagillin (75 mg/kg bw) compared with the negative control. However, with respect to the induction of Robertsonian translocations, both the intermediate (50 mg/kg bw) and highest (75 mg/kg bw) experimental dose caused a significant (p<0.001) increase (7.12+/-0.26 and 9.00+/-0.10, respectively) in comparison with the negative control (0.00+/-0.00). Chromosomes 4 and 19 participated in these Robertsonian translocations. Regarding total cytogenetic changes, a significant increase (p<0.001) was observed in both the intermediate dose group (17.36+/-1.83) and the highest dose group (59.49+/-1.92) compared with the negative control (7.00+/-1.35). These results suggest that fumagillin has genotoxic (clastogenic) potential in mammals in vivo.     

The mycorrhizal status of the woody Mediterranean shrub Myrtus communis L.

  Myrtus communis L. (myrtle), a typical Mediterranean plant species belonging to the family Myrtaceae, was shown to form arbuscular mycorrhizal symbioses in nature. Many different spore types were isolated from its rhizosphere and grown in pot cultures; six of them were identified as Glomus species. In the laboratory, the myrtle root system was colonized by indigenous endophytes as well as by an Italian isolate of Glomus intraradices. In greenhouse experiments, mycorrhizal inoculation reduced transplant stress in 60-day-old myrtle seedlings; their growth was renewed immediately after transplanting, whereas non-mycorrhizal plants stopped development. Significantly larger growth responses were obtained using indigenous fungi than the Italian isolate of Glomus intraradices. Accepted: 16 January 1997     

Subplate zone of the human brain: historical perspective and new concepts

Subplate zone (SP) is prominent, transient laminar compartment of the human fetal cerebral wall. The SP develops around 13 and gradually disappears after 32-34 postovulatory weeks. The SP neurons can be found as late as nine postnatal months, while remnants of the SP neurons can be traced until adult age in the form of interstitial neurons of the gyral white matter. SP is composed of postmigratory and migratory neurons, growth cones, loosely arranged axons, dendrites, glial cell and synapses. The remarkable feature of the SP is the presence of large amount of extracellular matrix. This feature can be used for delineation of SP in magnetic resonance images (MRI) of both, in vivo and post mortem brains. The importance of SP as the main synaptic zone of the human fetal cortex is based on the rich input of ,waiting,< afferents from thalamus and cortex, during the crucial phase of cortical target area selection. SP increases during mammalian evolution and culminates in human brain concomitantly with increase in number and diversity of cortico-cortical fibers. The recent neurobiological evidence shows that SP is important site of spontaneous endogeneous activity, building a framework for development of cortical columnar organization. The SP which can be readily visualized on conventional and DTI (diffusion-tensor-imaging) MRI in vivo, today is in the focus of interest of pediatric neurology due to the following facts: (1) SP is the site of early neural activity, (2) SP is the major substrate for functional plasticity, and (3) selective vulnerability of SP may lead to cognitive impairment.     

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The effects of the perinatal treatment with 5-hydroxytryptophan or tranylcypromine on the peripheral and central serotonin homeostasis in adult rats

Serotonin (5HT) is a biologically active amine present in mammals in the brain and the peripheral tissues. Autism is a neurodevelopmental disorder in which 5HT homeostasis is disturbed both centrally and peripherally, but the relationship between the 5HT disturbances in the two compartments is not understood. In an attempt to explore the relationship between the disturbed peripheral 5HT homeostasis and central 5HT functioning, we exposed the developing rat brain to increased 5HT concentrations, by treatment of rats with subcutaneous injections of the immediate 5HT precursor 5-hydroxy-l-tryptophan (5HTP, 25 mg/kg), or the non-selective MAO inhibitor tranylcypromine (TCP, 2 mg/kg), during the period of the most intensive development of 5HT neurons - from gestational day 13 to post-natal day 21. The effects of the mentioned treatments on peripheral and central 5HT levels were then studied in adult rats. Platelet and plasma 5HT concentrations (measured by ELISA), as well as cortical and midbrain 5HT, tryptophan and 5-hydroxyindoleacetic acid levels (measured by HPLC) were determined in twelve 5HTP treated and eight TCP treated rats, and compared with the values measured in 10 control, saline treated rats. Treatment with 5HTP significantly raised peripheral but not central 5HT concentrations. At adult age, peripheral 5HT homeostasis was re-established, while modest decrease in 5HT concentration was observed in frontal cortex, presumably due to hyperserotonemia-induced loss of 5HT terminals during brain development. Treatment with TCP induced significant 5HT elevations in both compartments. At adult age, permanent changes in 5HT homeostasis were observed, both peripherally (as hyperserotonemia) and centrally (as altered 5HT metabolism with decreased 5HT concentrations). Further studies are planned in order to explore the nature of the different disturbances of 5HT homeostasis induced by the two compounds, and their results are expected to shed some light on the role of hyperserotonemia in autism.     

Areal and laminar distribution of gangliosides in the fetal human neopallium at 28 weeks of gestation

Summary Correlative histological, histochemical and biochemical investigations on laminar compartments from four different areas of fetal human neopallium at 28 weeks of gestation revealed discrete distribution of gangliosides in the cerebral wall. Highest level of total ganglioside concentration was found in the layers of cortical anlage (cortical plate and subplate layer) which are concomittantly characterized by highest activity of acetylcholinesterase (AChE) and which are known to be involved in intensive synaptogenesis at this stage of cortical development. In three of four areas the proportion of GD1a — ganglioside from total ganglioside amount tended to increase and that of GT1b to decrease from inside (ventricle) to outside (cortical anlage) throughout the cerebral wall.     

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