Neurological disorders

A novel action of Alzheimer's amyloid-β-protein (Aβ): oligomeric Aβ promotes lipid release. Michikawa, M. et al. J. Neurosci. 21, 7226–7235 (2001) [PubMed]

The authors found that oligomeric Aβ stimulates the release of lipids, including cholesterol and phospholipids, from neurons and astrocytes in culture. Monomeric and fibrillar Aβ did not have the same effect. Lipid release was blocked by inhibition of protein kinase C and by addition of Congo red, which stabilizes Aβ monomers. So, the stimulation of lipid release from cell membranes and the disruption of lipid homeostasis might be an additional factor that contributes to the neuronal dysfunction observed in Alzheimer's disease.

Genetic suppression of seizure susceptibility in Drosophila. Kuebler, D. et al. J. Neurophysiol. 86, 1211–1225 (2001) [PubMed]

Kuebler and his colleagues advocate the use of Drosophila as a model system to study seizure susceptibility. They studied flies that are particularly prone to electric-shock-induced seizures — the so-called 'bang-sensitive mutants' — and looked for factors that could suppress the increased susceptibility. They performed crosses between the bang-sensitive mutants and flies with mutations in Na+, K+ and gap-junction channels, and identified double mutants with reduced seizure susceptibility. These findings set the scene for larger-scale screens to search for additional seizure-related candidate genes.

Synaptic physiology

Glutamate-induced transient modification of the postsynaptic density. Dosemeci, A. et al. Proc. Natl Acad. Sci. USA 98, 10428–10432 (2001) [PubMed]

Rapid formation and remodeling of postsynaptic densities in developing dendrites. Marrs, G. S. et al. Nature Neurosci. 27 August 2001 (10.1038/nn717) [PubMed]

Two new studies emphasize the dynamic nature of the postsynaptic density — the specialized complex of receptors, signal transduction molecules and other proteins found on the postsynaptic membrane. Dosemeci et al. found that the postsynaptic density thickens during synaptic activity induced by glutamate or brief depolarization of the presynaptic neuron. They also show that the thickening is reversible and results, at least in part, from translocation of calcium/calmodulin-dependent protein kinase II (CaMKII) to the postsynaptic density. This transient thickening could allow the postsynaptic density to adjust itself in response to changing synaptic activity. Marrs et al. investigated the formation and remodelling of the postsynaptic density in developing hippocampal neurons, and found that it was structurally dynamic: postsynaptic densities could appear or disappear within less than 15 minutes, grow, shrink or move. Such plasticity could enable rapid changes in synaptic connections in the developing brain.