Excitotoxic versus apoptotic mechanisms of neuronal cell death in perinatal hypoxia/ischemia

Hypoxic/ischemic (H/I) neuronal degeneration in the developing central nervous system (CNS) is mediated by an excitotoxic mechanism, and it has also been reported that an apoptosis mechanism is involved. However, there is much disagreement regarding how excitotoxic and apoptotic cell death processes relate to one another. Some authors believe that an excitotoxic stimulus directly triggers apoptotic cell death, but this interpretation is largely speculative at the present time. Our findings support the interpretation that excitotoxic and apoptotic neurodegeneration are two separate and distinct cell death processes that can be distinguished from one another by ultrastructural evaluation. Here we review evidence supporting this interpretation, including evidence that H/I in the developing CNS triggers two separate waves of neurodegeneration, the first being excitotoxic and the second being apoptotic. The first (excitotoxic) wave destroys neurons that would normally provide synaptic inputs or synaptic targets for the neurons that die in the second (apoptotic) wave. Since neurons, during the developmental period of synaptogenesis, are programmed to commit suicide if they fail to achieve normal connectivity, this explains why neuroapoptosis occurs following H/I in the developing CNS. However, it does not support the interpretation that H/I directly triggers apoptotic neurodegeneration. Rather, it documents that H/I directly triggers excitotoxic neurodegeneration, and apoptotic neurodegeneration ensues subsequently as the natural response of developing neurons to a specific kind of deprivation - loss of the ability to form normal synaptic connections.     

Characterisation of<Emphasis Type="Italic">fusarium graminearum</Emphasis> and<Emphasis Type="Italic">F. culmorum</Emphasis> isolates by mycotoxin production and aggressiveness to wheat

A total of 27Fusarium culmorum isolates from Germany and 41F. graminearum isolates from Kenya were investigated for aggressiveness and mycotoxin production on wheat ears. In addition, ergosterol content of the kernels from ears inoculated withF. graminearum was determined and theF. culmorum isolates were tested for mycotoxin productionin vitro. For both pathogens, isolates markedly differed in aggressiveness. 59% and 37% of theF. culmorum isolates produced NIV and DON, respectively,in vivo andin vitro. The DON-producing isolates also produced 3-acDONin vitro. The more aggressive isolates produced mainly DON while the less aggressive isolates produced mainly NIV. 12% and 85% of theF. graminearum isolates produced NIV and DON, respectively. The highly aggressive isolates produced higher amounts of DON, aggressiveness being highly correlated to DON content in the kernels. NIV-producing isolates were less aggressive. Ergosterol content of kernels was moderately correlated to aggressiveness but highly correlated to DON content. Disease severity was associated with kernel weight reduction.     

Age-related changes in glutamate concentration and synaptosomal glutamate uptake in adult rat striatum

It has been suggested that Glutamate (Glu), which has neurotoxic properties and is thought to be the excitatory neurotransmitter release at corticostriatal synapses, might play a role in neurological disorders involving the striatum. To establish normative data which may serve as baseline for evaluating experimental evidence relevant to this proposal, we have studied Glu concentrations and synaptosomal Glu high affinity uptake kinetics in the striatum of male and female rats at various ages from 3 to 19 months. Here we report that all parameters studied (Glu levels, Vmax and Km of uptake) undergo significant changes with advancing age. Striatal Glu concentrations are consistently in the range of 12 mmol/kg wet weight in early adult life (3–6 months) but drop to 10 mmol/kg by 10 months and 9.6 mmol/kg by 19 months (an overall 20% decrease). Concomitantly, significant reductions in Vmax and km of the Glu high affinity transport system occur, suggesting an age-related loss in the number of high affinity Glu transport sites and a compensatory increase in affinity of remaining sites for Glu. Tentatively we propose that degenerative changes in the putatively glutamergic corticostriatal tract, as a normal aspect of aging, is the simplest and most likely explanation for the observed changes. If such changes with normal aging also occur in humans, this must be taken into consideration in the interpretation of studies pertaining to the possible role of Glu in neurological disorders.     

Ecological correlates of population density and behavior in the circumtropical black triggerfish Melichthys niger (Balistidae)

The remarkable swarming of black triggerfish Melichthys niger (Balistidae) on oceanic islands led us to undertake a comparative ecological study of high-density and low-density populations of this unusual circumtropical species. Abundance, distribution, and aggressive encounters were recorded in the field from the high-density Johnston Atoll (JA) population, the low-density Belize (BE) population, and a local high-density aggregation from Puerto Rico (PR). JA and PR populations of M. niger occurred at significantly higher densities and were more aggregated than in BE. Intraspecific aggression (chases/min/fish) was an order of magnitude higher in BE than in JA, while interspecific aggression was similar among sites. Size frequency, growth rate, diet composition, body condition (liver-somatic index LSI) were assessed from collected specimens. JA grew more slowly than BE as determined by back-calculations from dorsal spine rings, suggesting density-dependent growth limitation. Size frequency analysis reflected this difference with significantly more large fish in the BE sample. Maximum age of triggerfish in both populations was estimated at 11 years, and 35–40% of growth occurred in the first year. Diet composition was similar in all three locations and indicated broad omnivory. Percent organic composition of gut contents (food quality measure) and LSI (body condition assay) were both significantly higher in the PR population, but no difference was detected between JA and BE. An increase in consumption of algae on the degraded PR reef may explain this pattern.     

Mapping of the human complement factor I gene to 4q25

A detailed genetic and physical map of human complement factor I (IF) using somatic cell hybrids, in situ hybridization, and genetic linkage is reported. The gene has been localized to band 4q25. The order GC-INP10-ADH3-EGF-IF-IL2-MNS is proposed for genes on 4q on the basis of genetic and physical mapping techniques. A BclI polymorphism found with the IF probe demonstrated a maternal origin for a de novo deletion of chromosome 4 that was used in physically mapping the gene. The genetic and physical distances around band 4q24 suggest that 1 cM is approximately 1.2 million bp of DNA. This work provides a useful addition to the map of 4q.