Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles.

Melanin, the pigment in hair, skin, eyes, and feathers, protects external tissue from damage by UV light. In contrast, neuromelanin (NM) is found in deep brain regions, specifically in loci that degenerate in Parkinson's disease. Although this distribution suggests a role for NM in Parkinson's disease neurodegeneration, the biosynthesis and function of NM have eluded characterization because of lack of an experimental system. We induced NM in rat substantia nigra and PC12 cell cultures by exposure to l-dihydroxyphenylalanine, which is rapidly converted to dopamine (DA) in the cytosol. This pigment was identical to human NM as assessed by paramagnetic resonance and was localized in double membrane autophagic vacuoles identical to NM granules of human substantia nigra. NM synthesis was abolished by adenoviral-mediated overexpression of the synaptic vesicle catecholamine transporter VMAT2, which decreases cytosolic DA by increasing vesicular accumulation of neurotransmitter. The NM is in a stable complex with ferric iron, and NM synthesis was inhibited by the iron chelator desferrioxamine, indicating that cytosolic DA and dihydroxyphenylalanine are oxidized by iron-mediated catalysis to membrane-impermeant quinones and semiquinones. NM synthesis thus results from excess cytosolic catecholamines not accumulated into synaptic vesicles. The permanent accumulation of excess catechols, quinones, and catechol adducts into a membrane-impermeant substance trapped in organelles may provide an antioxidant mechanism for catecholamine neurons. However, NM in organelles associated with secretory pathways may interfere with signaling, as it delays stimulated neurite outgrowth in PC12 cells.

Clustering of attempted suicide: New Zealand national data.

BACKGROUND: The extent to which clusters of attempted suicides occur is a significant problem that is complementary to the current available research on the clustering of completed suicide. However, little systematic research on clusters of attempted suicides exists. The present study examines the extent and nature of clustering of suicide attempts. METHOD: The occurrence of clustering of attempted suicide was examined in nationwide data for all New Zealand hospitals, obtained from the New Zealand Health Statistics Services for the years 1988-1990. The Scan statistic and Knox procedure were employed for testing the significance of clusters in time and time-space, respectively. RESULTS: The analyses indicated that significant time clustering occurred in younger age groups, specifically among 15-19 and 20-24 year olds. The results could not be accounted for by seasonal variations in admissions. Age specificity of time-space clusters emerged, exhibiting a similar pattern to that reported for completed suicides in the US. CONCLUSIONS: The results suggest a similar underlying mechanism for the clustering of parasuicide and completed suicides and provide support for the existence of contagion of suicidal behaviour. The implications for prevention are discussed.

Suicide clusters: an examination of age-specific effects.

The age specificity of time-space clusters of suicide was examined using National Center for Health Statistics data for 1978-84. Significant clustering of suicide occurred primarily among teenagers and young adults, with minimal effect beyond 24 years of age. Clustering was two to four times more common among adolescents and young adults than among other age groups.