Neurological disorders

Mutant protein in Huntington disease is resistant to proteolysis in affected brain. Dyer, R. B. & McMurray, C. T. Nature Genet. 29, 270–278 (2001) [PubMed]

Although the cause of Huntington's disease is unknown, one leading theory is that the expanded huntingtin protein is cleaved and that the amino-terminal fragments accumulate, causing cell death. However, Dyer and McMurray have now shown that the mutant huntingtin protein is relatively resistant to proteolysis. They propose instead that the full-length mutant protein causes toxicity by sequestering full-length and cleaved normal huntingtin.

Opioid receptors

Prolonged morphine treatment targets δ-opioid receptors to neuronal plasma membranes and enhances δ-mediated antinociception. Cahill, C. M. et al. J. Neurosci. 21, 7598–7607 (2001) [PubMed]

Opioid receptor ligands can cause complex regulatory changes in the receptor, and it has been proposed that the three different subtypes of opioid receptor can interact. Cahill et al. found evidence in support of this idea by showing that prolonged treatment with morphine, a μ-receptor agonist, can cause a marked increase in the density of δ-opioid receptors at the cell surface, both in vitro and in vivo. The receptor density increase was accompanied by potentiation of the anti-nociceptive effect of a δ-receptor agonist.

Neurotechniques

Delivery of the Cre recombinase by a self-deleting lentiviral vector: efficient gene targeting in vivo. Pfeifer, A. et al. Proc. Natl Acad. Sci. USA 98, 11450–11455 (2001) [PubMed]

In genetic engineering, crossbreeding of mice carrying genes flanked by loxP sites and those expressing the Cre recombinase is often used to generate region-specific knockout mice. Region-specific Cre expression can be achieved through viral transfection, but this can give rise to a strong immune response. Pfeifer et al. describe the use of lentiviral vectors to deliver Cre. To avoid toxicity, they designed a Cre transgene that is itself excised by Cre, so that the gene is expressed only for a short time before being deleted.

Neurotechniques

A miniature head-mounted two-photon microscope: high-resolution brain imaging in freely moving animals. Helmchen, F. et al. Neuron 31, 903–912 (2001) [PubMed]

Helmchen et al. have developed a head-mounted two-photon microscopy system that allows in vivo imaging of the cortex in awake, freely moving rats. Two-photon microscopy allows the detection of fluorescence down to imaging depths of around 0.5 mm; in the head-mounted system, it could be used to obtain images of blood vessels filled with fluorescently labelled blood, or pyramidal neurons labelled with a calcium indicator. This should allow the measurement of blood flow or calcium transients in response to physiological stimuli.