De novo aging-related megaloneurites: alteration of NADPH diaphorase positivity in the sacral spinal cord of the aged dog

Abstract

The aging-related changes of NADPH-diaphorase (NADPH-d) in the spinal cord were studied in aged dogs. At all levels of the spinal cord examined, NADPH-d activities were present in neurons and fibers in the superficial dorsal horn, dorsal commissure and in neurons around the central canal. In addition, the sympathetic autonomic nucleus in the thoracic and rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the sacral parasympathetic nucleus (SPN) in the sacral segments was not well stained. Interestingly, we found abundant NADPH-d positive enlarged-diameter fibers termed megaloneurite, which characteristically occurred in the aged sacral segments, distributed in the dorsal gray commissure (DGC), lateral collateral pathway (LCP) the lateral fasciculi and the central canal compared with the cervical, thoracic and lumbar segments. The dense, abnormal NADPH-d megaloneurites occurred in extending from dorsal entry zone through lamina I along with the lateral boundary of the dorsal horn to the region of the SPN. These fibers were prominent in the S1-S3 segments but not in adjacent segments L5-L7 and Cx1 or in thoracolumbar segments and cervical segments. Double staining with GFAP, NeuN, CGRP, MAP2 and Iba1, NADPH-d megaloneurite colocalized with vasoactive intestinal peptide. Presumably, the megaloneurites may represent, in part, visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.

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

“…Our hypothesis pointed out that N-d alterations in the GR (Ma et al, 1997) was correlated to ANB in the sacral segment (Tan et al, 2006) of the aging rats. We also found another kind of N-d neurodegeneration, megaloneurites (N-d meganeurites) in aged dogs (Li et al, 2018). Different to ANB in aged rats, N-d meganeurites are swelling and larger diameter neurites occurred in the dorsal root entry zoom, dorsal horn, lateral collateral pathway, Lissauer's tract, IML and DCN in aged dogs (Li et al, 2018).…”

Pial surface CSF-contacting texture, subpial and funicular plexus in the thoracic spinal cord in monkey: NADPH diaphorase histological configuration

“…We may also postulate that degeneration of NADPH-d funicular neurons could cause sensory-somatic dysfunction with aging, if it functioned as mechanical sensor. We do find that NADPH-d dystrophic neurites occur around the central canal in aged dog [15]. Next in our future experiments, we should identify Pkd2l1 expression in the NADPH-d funicular neurons for its maintenance of spine curvature [60].…”

“…Enkephalin positive fibers are also detected in the lateral funiculus of rat [51]. Recently, we reported that VIP neurodegenerative megaloneurites are detected in the sacral spinal cord in the aged dog [15]. It demonstrates that both VIP and NADPH-d CSF contacting structures exist in the spinal cord.…”

“…Next in our future experiments, we should identify Pkd2l1 expression in the NADPH-d funicular neurons for its maintenance of spine curvature [60]. In aged dog, Reissner's fiber, a "central body" or a "bud" [27]could be NADPH-d positive reaction [15]. In relative lower vertebra, such as fish, there is a specialized structure, urophysis related to neurosecretory cells [78] .…”

“…NADPH-d positive neurons have been detected in the spinal cord [13,14].The distribution of NADPH-d neurons are majorly detected in superficial dorsal horn, deeper laminae dorsal horn, Laminae X and IML. NADPH-d neurons is scarcely found in ventral horn in rat, but can be detected in the dog [15] and pigeon [16]. Occasionally, positive neurons are detected in the white matter [14].…”