Dual forms of aging-related NADPH diaphorase neurodegeneration in the sacral spinal cord of aged non-human primates

We discovered two different anomalous NADPH diaphorase (NADPH-d) positive alterations, which were expressed as aging-related NADPH-d positive spheroidal bodies and megaloneurites specially distributed in the superficial dorsal horn, dorsal gray commissure (DGC), lateral collateral pathway (LCP) and sacral parasympathetic nucleus (SPN) in the aged monkeys’ sacral spinal cord, compared with the cervical, thoracic and lumbar segments. In the gracile nucleus of aged monkeys, only aging-related spheroidal bodies were observed and no megaloneurites occurred. The dense, abnormal NADPH-d positive megaloneurites, extremely different from regular NADPH-d positive fibers, were prominent in the sacral segments and occurred in extending from Lissauer’s tract (LT) through lamina I along the lateral boundary of the dorsal horn to the region of the SPN. Meanwhile, large diameter punctate NADPH-d activity occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone (DREZ) at the same level of NADPH-d abnormality in the gray matters. Those dot-like NADPH-d alterations were examined by horizontal sectioning and indicated ascending or descending oriental fibers. These NADPH-d megaloneurites had the same composition as the punctate NADPH-d alterations and were co-localized with the VIP immunoreaction, while the ANBs did not coexist with the VIP immunoreaction. Both ANBs and megaloneurites provide consistent evidence that the anomalous neuritic alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.