A comparative analysis of the distribution of prosomatostatin‐derived peptides in human and monkey neocortex

Abstract

Comparative analyses were made of the immunohistochemical and biochemical distributions of three prosomatostatin‐derived peptides (PSDP) in human, perfused monkey, and unperfused monkey neocortex. The PSDP we examined were the tetradecapeptide somatostatin 14 (SS14); the N‐terminal extension of this peptide, somatostatin 28 (SS28); and somatostatin 28_1–12 (SS28_1–12). In immunohistochemical experiments, numerous SS28‐immunoreactive perikarya were located in both superficial and deep layers of perfused monkey cortex, but none were present in the cerebral cortex from unperfused monkey or autopsied human brains. In contrast, the number of SS28_1–12‐immunoreactive neurons was five times greater in the superficial cortical layers of unperfused monkey than of perfused monkey brain. Moreover, unperfused monkey and human cortex contained notably more SS14‐immunoreactive processes than perfused monkey cortex. These data suggested that SS28 may have been converted into SS14 and SS28_1–12 in unperfused tissue during the post‐mortem interval. This hypothesis was examined biochemically by measuring the levels of immunoreactivity of SS14, SS28, and SS28_1–12 in samples of unperfused monkey cortex frozen at different time intervals after removal from the brain. Samples frozen 10 minutes or longer after removal contained only 10–20% the level of SS28 immunoreactivity measured in samples frozen immediately or 1 minute after removal. The levels of SS14 and SS28_1–12 immunoreactivity did not demonstrate such reductions, and may instead have increased at early time points. To further characterize post‐mortem effects on PSDP and to explore for species differences, we performed a detailed comparison of the regional, laminar, and cellular distribution of SS28_1–12 immunoreactivity under the three conditions. A progressive loss of immunoreactivity, particularly in radial fibers, was found at increasing post‐mortem intervals in unperfused monkey neocortex, indicating that differences in density and distribution of immunoreactive fibers between human and perfused monkey may result from post‐mortem peptide degradation in unperfused tissue. In contrast, the larger size of SS28_1–12‐immunoreaetive white matter neurons in humans as compared to monkeys appeared partially due to a post‐mortem effect but also reflected a species difference. In addition, the density of white matter neurons was found to be significantly greater in human than in perfused or unperfused monkey. These data indicate that any study of human autopsy material must be assessed in light of possible post‐mortem effects. Although studies of perfused monkey cortex may yield data that more accurately reflect the normal distribution of PSDP in neocortex, one cannot rely exclusively upon these data as a predictor of the distribution of PSDP in human neocortex because species differences exist. Thus, evaluation of the role of chemically identified neural systems in human neocortex may be more effectively made if studies of human autopsy material are augmented by comparisons to both perfused and unperfused nonhuman primates.