Narrow Results

Two main processes concurrently refine the nervous system over the course of development: cell death and selective synaptic pruning. We simulated large spiking neural networks (100 × 100 neurons "at birth") characterized by an early developmental phase with cell death due to excessive firing rate, followed by the onset of spike timing dependent synaptic plasticity (STDP), driven by spatiotemporal patterns of stimulation. The cell death affected the inhibitory units more than the excitatory units during the early developmental phase. The network activity showed the appearance of recurrent spatiotemporal firing patterns along the STDP phase, thus suggesting the emergence of cell assemblies from the initially randomly connected networks. Some of these patterns were detected throughout the simulation despite the activity-driven network modifications while others disappeared.

Neurodegenerative disorders are accompanied by altered compositions of metals that may convey some information about the health and possibly metabolic state of neurons. Here we opted for PIXE technique to perform a spatially-resolved elemental analysis of intracellular space of individual neurons. Primarily, we measured element distribution within Purkinje cells (PC) of normal and Lurcher (Lc/+) mutant mice to detect any anomalies in concentrations of individual elements attributable to cell death. Lc/+ mutant mice provide an excellent animal model for time-course of excitotoxic cell death. PCs, some with autofluorescence, were scanned with a proton beam to record their X-ray emission and RBS spectra and to construct 2D-concentration maps of individual elements. PCs with auto-fluorescence, presumed to be either already dead or moribund, showed elevated concentrations of Cu, Fe, and Zn, when compared to healthy PCs. In conclusion, excitotoxic mode of death, as observed in the moribund PCs of Lc/+ cerebellum, may activate enzymatic processes, manifested as increased intracellular concentrations of Cu and Zn that are possibly constituents of some metalloenzyme complexes.

Caesalpinia sappan L. (C. sappan) has been used in Oriental medicine as an antitumor agent. The present study shows the effects of the chloroform extract of C. sappan on cell death in head and neck cancer cell lines. The viability of HNSCC4 and HNSCC31 cells (head and neck cancer cell lines) was noticeably decreased compared to that of HaCaT cells (control group) in the presence of chloroform extract. No significant difference was observed in the viability of HNSCC4 and HNSCC31 cells when compared with HaCaT cells in the presence of n-butanol, methanol, and water extracts. Exposure to the chloroform extract of C. sappan resulted in an increase in the Sub-G1 phase of the cell cycle and condensation and shrinkage of nuclei in the HNSCC4 and HNSCC31 cells. The levels of p53 and p21^WAF1/CIP1 were also increased in the HNSCC4 and HNSCC31 cells. The results suggest that the chloroform extract of C. sappan may increase cell death in the HNSCC4 and HNSCC31 cells, which is linked to increased cellular levels of p53 and p21^WAF1/CIP1.