ALTERATION OF PROTEASE LEVELS IN DIFFERENT BRAIN-AREAS OF SUICIDE VICTIMS

Numerous recent studies found that proteases play a major role in brai n function. In addition to their role in protein turnover, they have m odulatory functions and an important role in apoptosis, pathological c hanges, and other mechanisms. To explore possible differences in brain protein metabolism of suicide victims, we examined the activity of tw o proteases, cathepsin D and calpain (I and II combined), in eleven di screte areas of postmortem brain tissue of 21 victims of suicide and o f 31 age- and sex-matched control subjects without a history of psychi atric or neurological disease. The levels of functionally Important am ino acids in five of these areas were also measured. Cathepsin D activ ity was found to be lower in two of eleven regions of brains of suicid e victims, the parahippocampal cortex and the medial hypothalamus, by 26% and 27%, respectively. Calpain activity was lower in two different areas tested, 29% in the medulla oblongata and 26% in the lateral pre frontal cortex, and was 18% higher in the midbrain. There were no sign ificant differences in the other areas (globus pallidus, hippocampus, amygdala, caudate nucleus, ventral tegmental area, and nucleus accumbe ns). Protease distribution was regionally heterogeneous-the levels in the globus pallidus were low, and in the hippocampus high, with about a two-fold difference. The length of the postmortem period for obtaini ng tissue, the storage time of the frozen tissue, and the age of the s ubject had no apparent influence on the results obtained. Although the re was a tendency toward higher levels of aspartate and glycine in bra in areas from suicide victims, the difference was not significant. The variations among individual brains were greater in amino acid levels than in protease levels. The findings indicate the possible role of pr otein metabolism in depressive or suicidal behavior.