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

2018 ◽  
Author(s):  
Yinhua Li ◽  
Yunge Jia ◽  
Wei Hou ◽  
Zichun Wei ◽  
Xiaoxin Wen ◽  
...  

AbstractThe 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.

2019 ◽  
Author(s):  
Yinhua Li ◽  
Zichun Wei ◽  
Yunge Jia ◽  
Wei Hou ◽  
Yu Wang ◽  
...  

AbstractWe 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.


2008 ◽  
Vol 53 (No. 8) ◽  
pp. 434-444 ◽  
Author(s):  
J. Calka ◽  
M. Zalecki ◽  
K. Wasowicz ◽  
M.B. Arciszewski ◽  
M. Lakomy

Present knowledge concerning the organization of cholinergic structures of the spinal cord has been derived primarily from studies on small laboratory animals, while there is a complete lack of information concerning its structure in the pig. In the present study we employed choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry to identify the cholinergic neuronal population in the thoracolumbar and sacral spinal cord of the pig. The distribution of ChAT-, VAChT- and AChE-positive cells was found to be similar. Distinct groups of cholinergic neurons were observed in the gray matter of the ventral horn, intermediolateral nucleus, intermediomedial nucleus as well as individual stained cells were found in the area around the central canal and in the base of the dorsal horn. Double staining confirmed complete colocalization of ChAT with AChE in the ventral horn and intermediolateral nucleus although in the intermediomedial nucleus only 64% of the AChE-positive neurons expressed ChAT-immunoreactivity, indicating unique, region restricted, diversity of ChAT and AChE staining. Our results revealed details concerning spatial distribution and morphological features of the cholinergic neurons in the thoracolumbar and sacral spinal cord of the pig. We also found that the pattern of distribution of cholinergic neurons in the porcine spinal cord shows great similarity to the organization of the cholinergic system in other mammalian species studied.


2020 ◽  
Author(s):  
Yunge Jia ◽  
Yinhua Li ◽  
Wei Hou ◽  
Fuhong Li ◽  
Haoran Sun ◽  
...  

ABSTRACTThe spinal cord is a cylinder structure in the vertebra and thought a simplified with the gray matter and white matter. Rexed lamination for the gray matter and regional sub-division for whiter matter are completely termed to date. Anterior commissure locates between the central canal and the anterior median fissure. However, some experimental data may still confront with new confined anatomical interpretation. By using NADPH diaphorase [N-d] enzyme histology, we found a vertical oriented neuronal pathway between the central canal and the anterior median fissure in the sacral spinal cord of young adult and aged dog. We used a term “supra fissure area” [SFA] to illustrate the region which consisted of the gray commissure and anterior white commissure. The N-d pathway was notably observable in aged animals. The vertical neurites revealed the cerebrospinal fluid [CSF] contacting neurites between the anterior median fissure and the central canal. We further examined the monkey, rat and pigeon in the region for better understanding of the structure and potential function. The neurodegeneration of N-d dystrophy was detected in the [SFA] in the thoracic spinal cord of the aged monkey. N-d positive fibers were detected in anterior fissure of the rat spinal cord. N-d fibrous structures were also detected in the pigeon spinal cord. These results suggested a new pathway of CSF contacting neurons and the neuronal communications about the central canal.


2020 ◽  
Vol 16 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Jin-Rong He ◽  
Shu-Guang Yu ◽  
Yong Tang ◽  
Peter Illes

Abstract This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain. In addition, during AP/EAP non-neuronal P2X4 and/or P2X7Rs localized at microglial cells of the CNS become activated at the spinal or supraspinal levels. In consequence, these microglia secrete bioactive compounds such as growth factors, cytokines, chemokines, reactive oxygen, and nitrogen species, which modulate the ascending neuronal pathways conducting painful stimuli. Alternatively, ATP released at acupoints by AP/EAP may be enzymatically degraded to adenosine, stimulating in loco presynaptic A1Rs exerting an inhibitory influence on the primary afferent fibers (the above mentioned pain-sensing peripheral terminals of DRG neurons) which thereby fail to conduct action potentials to the spinal cord dorsal horn. The net effect of the stimulation of P2X3, P2X4, P2X7, and A1Rs by the AP/EAP-induced release of ATP/adenosine at certain acupoints will be analgesia.


2000 ◽  
Vol 278 (4) ◽  
pp. R1027-R1039 ◽  
Author(s):  
Margaret A. Vizzard

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after cyclophosphamide (CYP)-induced bladder inflammation. In urethan-anesthetized Wistar rats with cystitis, intravesical saline distension significantly ( P ≤ 0.0005) increased the number of Fos-immunoreactive (IR) cells observed in the rostral lumbar (L1, 35 cells/section; L2, 27 cells/section) and caudal lumbosacral (L6, 120 cells/section; S1, 96 cells/section) spinal cord compared with control animals, but Fos protein expression in the L5 segment was not altered. The topographical distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. The majority of Fos-IR cells were distributed in the dorsal commissure (45%), with smaller percentages in the sacral parasympathetic nucleus (25%), medial dorsal horn (20%), and lateral dorsal horn (10%). These results demonstrate that urinary bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after cystitis. This altered distribution pattern resembles that following noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after cystitis. These data suggest that chronic cystitis can reveal a nociceptive Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus that is partially mediated by capasaicin-sensitive bladder afferents.


1985 ◽  
Vol 53 (4) ◽  
pp. 1059-1078 ◽  
Author(s):  
C. N. Honda

One hundred and sixty extracellularly and intracellularly recorded unitary discharges from the sacral or caudal spinal segments of 30 anemically decerebrated cats were studied to examine the effects of somatic and visceral afferent stimulation on neurons near the central canal (CC). The recorded unitary activity was histologically verified (by dye marks or horseradish peroxidase, HRP) as having come from the gray matter surrounding the CC that approximates Rexed's lamina X. In the absence of intentional stimulation or apparent injury by the recording electrode, 62% of the units exhibited ongoing discharges. Each unit was tested for responses to the stimulation of somatic (cutaneous and subcutaneous) and visceral (bladder and colon) structures. Seventy-six (48%) of the units responded exclusively to the stimulation of somatic receptive fields, and 10 (6%) of the units were selectively responsive to stimulation of the pelvic viscera. The activity of the remaining 74 (46%) was influenced by activity in both somatic and visceral afferent fibers. Eighteen of the 160 neurons were intracellularly marked with HRP. Based on perikaryal size and dendritic extent, it was possible to divide these cells into two partially overlapping groups. One group consisted of seven neurons with small to medium-sized perikarya, dendritic arbors largely restricted to the gray matter surrounding the CC, and small, singular somatic receptive fields. The second group comprised 11 cells with medium to large-sized soma and dendrites extending out of lamina X. These larger neurons usually possessed multiple, widely distributed somatic receptive fields. The principal finding of the present study is that in the sacral spinal cord many cells near the CC receive primary afferent inputs converging from a wide range of receptor types in somatic and visceral structures. Such neurons are capable of integrating afferent information from somatic structures on both sides of the body with information originating in pelvic viscera and midline regions such as the genitals.


2012 ◽  
Vol 303 (3) ◽  
pp. F350-F356 ◽  
Author(s):  
Wenbin Yang ◽  
Charles N. Rudick ◽  
Eneda Hoxha ◽  
Stephen A. Allsop ◽  
Jordan D. Dimitrakoff ◽  
...  

Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. Interstitial cystitis is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area. In this study, we used a murine neurogenic cystitis model to identify genes participating in the development of pelvic pain. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic pain. The sacral spinal cord was harvested on postinfection days (PID) 2 and 4, and gene expression was analyzed by microarrays and confirmed by quantitative RT-PCR. On PID 2, the overall expression profile was similar to that of uninfected sacral spinal cord; by PID 4, there were substantial differences in expression of multiple functional classes of genes, especially inflammation. Analysis of pain-signaling pathways at the dorsal horn suggested that Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain. Consistent with this, CaMKIIδ expression exhibited a mast cell-dependent increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII immunoreactivity in the dorsal horn was increased on postinfection day (PID) 4 during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN-93 attenuated the PRV pain response. These data suggest that CaMKII plays a functional role in pelvic pain due to neurogenic cystitis.


1996 ◽  
Vol 75 (6) ◽  
pp. 2606-2628 ◽  
Author(s):  
J. T. Katter ◽  
R. J. Dado ◽  
E. Kostarczyk ◽  
G. J. Giesler

1. A goal of this study was to determine whether neurons in the sacral spinal cord that project to the diencephalon are involved in the processing and transmission of sensory information that arises in the perineum and pelvis. Therefore, 58 neurons in segments L6-S2 were activated antidromically with currents < or = 30 microA from points in the contralateral diencephalon in rats that were anesthetized with urethan. 2. Responses to mechanical stimuli applied to the cutaneous receptive fields of these neurons were used to classify them as low-threshold (LT), wide dynamic range (WDR) or high-threshold (HT) neurons. Twenty-two neurons (38%) responded preferentially to brushing (LT neurons). Eighteen neurons (31%) responded to brushing but responded with higher firing frequencies to noxious mechanical stimuli (WDR neurons). Eighteen neurons (31%) responded only to noxious intensities of mechanical stimulation (HT neurons). LT neurons were recorded predominantly in nucleus proprius of the dorsal horn. Nociceptive neurons (WDR and HT) were recorded throughout the dorsal horn. 3. Cutaneous receptive fields were mapped for 56 neurons. Forty-five (80%) had receptive fields that included at least two of the following regions ipsilaterally: the rump, perineum, or tail. Eleven neurons (20%) had receptive fields that were restricted to one of these areas or to the ipsilateral hind limb. Thirty-eight neurons (68%) had cutaneous receptive fields that also included regions of the contralateral tail or perineum. On the perineum, receptive fields usually encompassed perianal and perivaginal areas including the clitoral sheath. There were no statistically significant differences in the locations or sizes of receptive fields for LT neurons compared with nociceptive (WDR and HT) neurons. 4. Thirty-seven LT, WDR, and HT neurons were tested for their responsiveness to heat stimuli. Five (14%) responded to increasing intensities of heat with graded increases in their firing frequencies. Thirty-two LT, WDR, and HT neurons also were tested with cold stimuli. None responded with graded increases in their firing frequencies to increasingly colder stimuli. There were no statistically significant differences among the responses of LT, WDR, and HT neurons to either heat or cold stimuli. 5. Forty LT, WDR, and HT neurons were tested for their responsiveness to visceral stimuli by distending a balloon placed into the rectum and colon with a series of increasing pressures. Seventeen (43%) exhibited graded increases in their firing frequencies in response to increasing pressures of colorectal distention (CrD). None of the responsive neurons responded reproducibly to CrD at an intensity of 20 mmHg, and all responded at intensities of > or = 80 mmHg. More than 90% responded abruptly at stimulus onset, responded continuously throughout the stimulus period, and stopped responding immediately after termination of the stimulus. 6. Thirty-one neurons were tested for their responsiveness to distention of a balloon placed inside the vagina. Eleven (35%) exhibited graded increases in their firing frequencies in response to increasing pressures of vaginal distention (VaD). The thresholds and temporal profiles of the responses to VaD were similar to those for CrD. Twenty-nine neurons were tested with both CrD and VaD. Thirteen (45%) were excited by both stimuli, four (14%) responded to CrD but not VaD, and one (3%) was excited by VaD but not CrD. Neurons excited by CrD, VaD, or both were recorded throughout the dorsal horn. 7. As a population, WDR neurons, but not LT or HT neurons, encoded increasing pressures of CrD and VaD with graded increases in their firing frequencies. The responses of WDR neurons to CrD differed significantly from those of either LT or HT neurons. Regression analyses of the stimulus-response functions of responsive WDR neurons to CrD and VaD were described by power functions with exponents of 1.6 and 2.4, respectively.(ABSTRACT TRUNCATED)


2003 ◽  
Vol 99 (1) ◽  
pp. 205-211 ◽  
Author(s):  
Chuanyao Tong ◽  
Weiya Ma ◽  
Sang-Wook Shin ◽  
Robert L. James ◽  
James C. Eisenach

Background Uterine cervical distension underlies labor pain, yet its neurophysiology and pharmacology of inhibition remain unexplored. The authors examined uterine cervical distension-evoked cFos immunoreactivity in rat spinal cords, and the inhibitory effect of spinal cyclo-oxygenase inhibition on cFos expression. Methods Female rats were anesthetized with halothane, and pairs of metal rods were inserted in each cervical os through a mid-line laparotomy. A submaximal distension force (75 g) was applied for either 30 or 60 min, or, in control animals, no force was applied. Other animals received cervical lidocaine infiltration prior to uterine cervical distension. At the end of the experiments, the spinal cord at T12 to L2 levels was harvested and immunostained for cFos protein. Other animals received intrathecal ketorolac (0, 5, 25, and 50 microg; n = 5-6 for each group) prior to uterine cervical distension. Results Uterine cervical distension significantly increased cFos immunoreactivity in the spinal cord from T12 to L2, with most cFos expression in the deep dorsal and central canal regions. Surgical preparation alone without uterine cervical distension resulted in minimal cFos expression, primarily in the superficial dorsal horn. Uterine cervical distension-evoked cFos expression was prevented by prior infiltration of lidocaine into the cervix. Intrathecal ketorolac produced a dose-dependent inhibition of uterine cervical distension-induced cFos expression. Conclusion The present study demonstrates that uterine cervical distension results in a similar pattern of spinal cord neuronal activation as seen with other noxious visceral stimuli. The inhibition of cFos expression by intrathecal ketorolac suggests that spinal cyclo-oxygenase plays a role in uterine cervical distension-induced nociception.


2020 ◽  
Author(s):  
Yunge Jia ◽  
Yinhua Li ◽  
Wei Hou ◽  
Huibing Tan

ABSTRACTNADPH diaphorase (N-d) neurons distribute in spinal cord and function for visceral sensation and autonomic regulation. N-d positive neurons innervate pelvic organs. In previous investigation, we report that aging-related N-d body (ANB) in the lumbosacral spinal cord in aged rat and megaloneurite in the sacral spinal cord in aged dog. This article was a continued data report of aging-related N-d alterations in aged dog. N-d positivity in aged spinal cord has revealed a certain of morphological profiles in the spinal cord of several species. However, we still found some denoted N-d neurodegenerative changes that we failed to notice in our previous studies when re-examination of the sacral spinal cord of aged dog. In the horizontal section, spacing spheroids in the superficial laminae of the dorsal horn, curl-up and coiled neurites in the intermediate zone were detected in the sacral spinal cord. The ANB and vacuolar neurite were also detected. Vacuolar degeneration also occurred in the dorsal ganglia at the sacral segment. The curl-up and coiled neurites did not occur in the lumbothoracic segment, but the ANB and vacuolar neurite were scatteringly detected in in the lumbothoracic segment of aged dog. The results suggested that the N-d sensory inputs interrupted and disconnected with integration of autonomic centers and output circuits of regulating urogenital organs during the aging. These specialized profiles were speculated that the N-d neurite deterioration of visceral sensory circuit implicated dysfunction of pelvic organs in the aging. Megaloneurite and fiber dilation may make backward reasoning to N-d fiber architecture under normal condition.


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