Metal binding of metallothioneins in human astrocytomas (U87 MG,IPDDC-2A)

Astroglia cells structurally and nutritionally support neurons in the central nervous system. They play an important role in guiding the construction of the nervous system and controlling the chemical and ionic environment of neurons. They also represent the major sites for accumulation and immobilisation of toxic metal ions most probably connected with metallothioneins. For this reason astroglia cells possess high cytosolic levels of metallothioneins I, II and III (MT-I,II,III). Our aim was to establish the inducibility and metal binding of MTs in two human astrocytoma cell lines, U87 MG (astrocytoma–glioblastoma, grade IV) and IPDDC-2A (astrocytoma, grade II), on exposure to cadmium chloride (1 μM). MTs were identified by molecular weight (size exclusion chromatography) and their metal content (Cd, Zn and Cu) to follow the interactions between metals. We showed that MTs are constitutively expressed in both human astrocytoma cell lines. In accordance with the higher malignancy grade of U87 MG, the amount of MTs was higher in U87 MG than in IPDDC-2A cells. After 24 hours of exposure to Cd their expression greatly increased in both cell lines and they were capable of immobilising almost all water soluble Cd. Induction of MTs in U87 MG cells was additionally followed up to 48 hours with exposure to different concentrations of CdCl₂ (1, 10 μM). Induction was a time dependent process throughout the period. Isoform III (identified by chromatographic separation of isoform III from I/II) was present at all exposure times, but only in traces with respect to the prevailing amounts of MT-I/II isoforms. So induction can be attributed to isoform I/II only.     

Cadmium and mercury cause an oxidative stress-induced endothelial dysfunction

We investigated the ability of cadmium and mercury ions to cause endothelial dysfunction in bovine pulmonary artery endothelial cell monolayers. Exposure of monolayers for 48 h to metal concentrations greater than 3–5 μM produced profound cytotoxicity (increased lactate dehydrogenase leakage), a permeability barrier failure, depletion of glutathione and ATP and almost complete inhibition of the activity of key thiol enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In contrast, metal concentrations less than 1–2 μM induced increases in glutathione and thiol-enzyme activities with minimal changes in LDH leakage, barrier function and ATP content. At shorter incubation times (24 h or less), high concentrations of cadmium caused glutathione induction rather than depletion. Thus, oxidative stress and cytotoxicity induced by lower concentrations of the metal ions stimulate compensatory responses, including increased synthesis of glutathione, which presumably preserved the activity of key thiol enzymes, however these responses were not sustainable at higher metal ion concentrations. We conclude, while high concentrations of heavy metals are cytotoxic, lower concentration induce a compensatory protective response, which may explain threshold effects in metal-ion toxicity.     

The function of habitat change during brood-rearing in the precocial Kentish plover <Emphasis Type="Italic">Charadrius alexandrinus</Emphasis>

Food availability is often variable during the breeding season. Parents with nonmobile, altricial young have no choice but to accept changes in local food availability, whereas in precocial animals, the parents may lead their young away from poor sites to areas that have rich resources and/or are safe from predators. We investigated the latter hypotheses in the Kentish plover Charadrius alexandrinus, a precocial shorebird that raises its young in two habitats: on lakeshore and in saltmarsh. Parents move with their broods from saltmarsh to lakeshore, especially late in the breeding season, and we hypothesized that lakeshores provide more food than the saltmarsh. Consistent with our hypotheses, plover chicks grew faster on the shore, and the difference in growth rates between the two habitats was amplified later in the breeding season. In addition, brood survival was higher on lakeshore than in saltmarsh and decreased with hatching date. Taken together, our results suggest that Kentish plover parents increase their reproductive success by switching brood-rearing habitats strategically.     

Effects of Male Age and Cervical Proprioceptors on Sexual Aerial Pursuit by Male Flesh Flies, <Emphasis Type="Italic">Neobellieria bullata</Emphasis> (Diptera: Sarcophagidae)

Information from multiple sensory systems is likely combined to provide guidance for male muscoid flies engaged in aerial pursuit of females. To specify the female’s position to the thoracic flight motor, head-centered visual information should be integrated with propriosensory information about head position relative to the thorax because the flies’ heads are flexible around the neck. Head position is encoded by a proprioceptive organ in the ventral neck membrane. We determined in the flesh fly Neobellieria bullata (Sarcophagidae) that accurate propriosensory information is necessary for aerial capture of females by shaving mechanosensory hairs from the organ in male flies and competing them against their sham operated brothers in pursuits of virgin females. We also determined that normal male flies are not successful at capturing females until the second day post-eclosion.     

Waste Management in the Leaf-Cutting Ant <Emphasis Type="Italic">Acromyrmex lobicornis</Emphasis>: Division of Labour,Aggressive Behaviour,and Location of External Refuse Dumps

In leaf-cutting ants, the handling of waste materials from the fungus culture increases the risk of infection. Consequently, ants should manage their waste in a way that minimizes the spread of diseases. We investigated whether in Acromyrmex lobicornis, waste-worker ants (a) also perform roles in foraging or mound maintenance, (b) are morphologically different than other ant workers, and (c) are aggressively discriminated by other worker ants from the same colony. In addition, we investigated whether the location of external waste piles minimizes the probability that wastes spread to the ant nest. In the field, we (a) marked with different colours waste-workers, foragers and mound-workers and monitored whether these ants interchanged their tasks; (b) measured head width, head length, hind femur length and total length of waste-workers; foragers and mound-workers; (c) forced field encounters between waste-workers and foragers, and (d) measured the cardinal orientation of the waste piles in relation to the colony mound. Waste-worker ants did not perform other function outside the nest; neither foragers nor mound-workers managed the waste. Moreover, waste-workers were smaller than foragers and mound-workers, and were attacked if they tried to enter their nest using foraging entrances. The location of external refuse dumps also appears to reduce contamination risks. Waste piles always were down-slope, and often followed the prevailing wind direction. The importance of behaviours such as the division of labour, aggressions against waste-workers and nest compartmentalization (i.e., the orientation of external waste piles) to minimize the spread of pathogens is discussed.     

Kinetics of Synaptic Transmission at Ribbon Synapses of Rods and Cones

The ribbon synapse is a specialized structure that allows photoreceptors to sustain the continuous release of vesicles for hours upon hours and years upon years but also respond rapidly to momentary changes in illumination. Light responses of cones are faster than those of rods and, mirroring this difference, synaptic transmission from cones is also faster than transmission from rods. This review evaluates the various factors that regulate synaptic kinetics and contribute to kinetic differences between rod and cone synapses. Presynaptically, the release of glutamate-laden synaptic vesicles is regulated by properties of the synaptic proteins involved in exocytosis, influx of calcium through calcium channels, calcium release from intracellular stores, diffusion of calcium to the release site, calcium buffering, and extrusion of calcium from the cytoplasm. The rate of vesicle replenishment also limits the ability of the synapse to follow changes in release. Post-synaptic factors include properties of glutamate receptors, dynamics of glutamate diffusion through the cleft, and glutamate uptake by glutamate transporters. Thus, multiple synaptic mechanisms help to shape the responses of second-order horizontal and bipolar cells.     

Cocaine withdrawal and neuro-adaptations in ion channel function

Chronic exposure to psychostimulants induces neuro-adaptations in ion channel function of dopamine (DA)-innervated cells localized within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Although neuroplasticity in ion channel function is initially found in drug-sensitized animals, it has recently been believed to underlie the withdrawal effects of cocaine, including craving that leads to relapse in human addicts. Recent studies have also revealed remarkable differences in altered ion channel activities between mPFC pyramidal neurons and medium spiny NAc neurons in cocaine-withdrawn animals. In response to psychostimulant or certain “excitatory” stimuli, increased intrinsic excitability is found in mPFC pyramidal neurons, whereas decreased excitability is observed in medium spiny NAc cells in drug-withdrawn animals compared to drug-free control animals. These changes in ion channel function are modulated by interrupted DA/Ca²⁺ signaling with decreased DA D2 receptor function but increased D1 receptor signaling. More importantly, they are correlated to behavioral changes in cocaine-withdrawn human addicts and sensitized animals. Based on growing evidence, researchers have proposed that cocaine-induced neuro-adaptations in ion channel activity and DA/Ca²⁺ signaling in mPFC pyramidal neurons and medium spiny NAc cells may be the fundamental cellular mechanism underlying the cocaine withdrawal effects observed in human addicts.     

Morphogenic Signaling in Neurons Via Neurotransmitter Receptors and Small GTPases

Several neurotransmitters including serotonin and glutamate have been shown to be involved in many aspects of neural development, such as neurite outgrowth, regulation of neuronal morphology, growth cone motility and dendritic spine shape and density, in addition to their well-established role in neuronal communication. This review focuses on recent advances in our understanding of the molecular mechanisms underlying neurotransmitter-induced changes in neuronal morphology. In the first part of the review, we introduce the roles of small GTPases of the Rho family in morphogenic signaling in neurons and discuss signaling pathways, which may link serotonin, operating as a soluble guidance factor, and the Rho GTPase machinery, controlling neuronal morphology and motility. In the second part of the review, we focus on glutamate-induced neuroplasticity and discuss the evidence on involvement of Rho and Ras GTPases in functional and structural synaptic plasticity triggered by the activation of glutamate receptors.     

Neurogenesis and Neuroprotection in the CNS — Fundamental Elements in the Effect of Glatiramer Acetate on Treatment of Autoimmune Neurological Disorders

Multiple sclerosis (MS) is no longer considered to be simply an autoimmune disease. In addition to inflammation and demyelination, axonal injury and neuronal loss underlie the accumulation of disability and the disease progression. Specific treatment strategies should thus aim to act within the central nervous system (CNS) by interfering with both neuroinflammation and neurodegeneration. Specific treatment strategies to autoimmune neurological disorders should aim to act within the CNS by interfering with both neuroinflammation and neurodegeneration. The cumulative effect of Glatiramer acetate (GA; Copaxone(R), Copolymer 1), an approved drug for the treatment of MS, reviewed herewith, draws a direct linkage between anti-inflammatory immunomodulation, neuroprotection, neurogenesis, and therapeutic activity in the CNS. GA treatment augmented the three processes characteristic of neurogenesis, namely, neuronal progenitor cell proliferation, migration, and differentiation. The newborn neurons manifested massive migration through exciting and dormant migratory pathways, into injury sites in brain regions, which do not normally undergo neurogenesis, and differentiated to mature neuronal phenotype, thus, counteracting the neurodegenerative course of disease. The plausible mechanism underlying this multifactorial effect is the induction of GA-reactive T cells in the periphery and their infiltration into the CNS, where they release immunomodulatory cytokines and neurotrophic factors in the injury site.