Immunohistochemical and chromatographic identification of peptides derived from proneuropeptide Y in the human frontal cortex

Proneuropeptide Y (proNPY) is posttranslationally processed to NPY(1-36)amide and the C-terminal flanking peptide of NPY (CPON). Antisera directed against the N-terminal part of NPY, CPON, or CysNPY(32-36)amide were used to identify peptide fragments processed from proNPY in biopsies of human frontal cortical specimens obtained from patients who underwent surgical treatment of profound cerebral tumors. Gel filtration and radioimmunoassays of human cortical extracts revealed that the NPY immunoreactivity was found only as NPY(1-36)amide, indicating that all NPY is present in an amidated form. In contrast, no intact proNPY was identified. NPY/CPON-immunoreactive neurons were observed to be nonspiny with long axonal processes mostly orientated longitudinally in the direction of the superficial layers. Bundles of immunoreactive fibers in the underlying white matter were orientated toward superficial layers of the neocortex, indicating a subcortical origin of some NPY/CPON nerve fibers. Axonal terminals were distributed throughout the neocortex, with highest numbers observed in layer I. Some fibers penetrated from the superficial layer I into the overlying pial surface. Many fibers were also observed in proximity to intracortical blood vessels, and some of these fibers originated from the cortical neurons, indicating that NPY could play a role as an intracortical autoregulator of the tonus of cerebral arterioles. Together these results indicate that NPY(1-36)amide and CPON are present in intracortical neurons as two independent molecules and that NPY may be involved in synaptic processes and regulation of blood flow in the human brain.