1.Spinal gastrin-releasing peptide system mediates sexual function of males: advances in studies.
Qing-Quan LIU ; Da-Wei YE ; Hong-Bing XIANG ; Ji-Hong LIU
National Journal of Andrology 2014;20(6):554-557
A collection of neurons in the upper lumbar spinal cord (lumbar segments 3 and 4) of male rats project to the lower lumbar spinal cord (lumbar segments 5 and 6) and release a gastrin-releasing peptide (GRP) to the somatic and autonomic regions, which are known to regulate male sexual reflexes. The GRP plays some special functions when bound to the specific GRP receptor (GRPR). The spinal GRP system is regulated by androgens. Accumulating evidence shows that GRP plays an important role in rat penile erection and ejaculation, and pharmacological stimulation of GRPRs with a specific agonist can restore penile reflexes and ejaculation in castrated male rats. Therefore, the GRP system appears to be a potential therapeutic target for the treatment of erectile dysfunction or ejaculatory dysfunction. The present paper briefly reviews the recent studies on the role of the spinal GRP system in regulating the sexual function of males.
Androgens
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metabolism
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Animals
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Ejaculation
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physiology
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Gastrin-Releasing Peptide
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metabolism
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physiology
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Male
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Penile Erection
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physiology
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Rats
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Spinal Cord
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metabolism
2.Correlation between magnetic resonance T2 image signal intensity ratio and cell apoptosis in a rabbit spinal cord cervical myelopathy model.
Lei MA ; Di ZHANG ; Wei CHEN ; Yong SHEN ; Yingze ZHANG ; Wenyuan DING ; Wei ZHANG ; Linfeng WANG ; Dalong YANG
Chinese Medical Journal 2014;127(2):305-313
BACKGROUNDCervical spondylotic myelopathy (CSM) is a common cause of disability in elderly patients. Previous studies have shown that spinal cord cell apoptosis due to spinal cord compression plays an important role in the pathology of myelopathy. Although changes in magnetic resonance imaging (MRI) T2 signal intensity ratio (SIR) are considered to be an indicator of CSM, little information is published supporting the correlation between changes in MRI signal and pathological changes. This study aims to testify the correlation between MRI T2 SIR changes and cell apoptosis using a CSM animal model.
METHODSForty-eight rabbits were randomly assigned to four groups: one control group and three experimental chronic compression groups, with each group containing 12 animals. Chronic compression of the cervical spinal cord was implemented in the experimental groups by implanting a screw in the C3 vertebra. The control group underwent sham surgery. Experimental groups were observed for 3, 6, or 9 months after surgery. MRI T2-weighted SIR Tarlov motor scores and cortical somatosensory-evoked potentials (CSEPs) were periodically monitored. At each time point, rabbits from one group were sacrificed to determine the level of apoptosis by histology (n = 6) and Western blotting (n = 6).
RESULTSTarlov motor scores in the compression groups were lower at all time points than the control group scores, with the lowest score at 9 months (P < 0.001). Electrophysiological testing showed a significantly prolonged latency in CSEP in the compression groups compared with the control group. All rabbits in the compression groups showed higher MRI T2 SIR in the injury epicenter compared with controls, and higher SIR was also found at 9 months compared with 3 or 6 months. Histological analysis showed significant apoptosis in the spinal cord tissue in the compression groups, but not in the control group. There were significant differences in apoptosis degree over time (P < 0.001), with the 9-month group displaying the most severe spinal cord apoptosis. Spearman's rank correlation test showed that there was close relation between MRI SIR and degree of caspase-3 expression in Western blotting (r = 0.824. P < 0.001).
CONCLUSIONSClear apoptosis of spinal cord tissue was observed during chronic focal spinal compression. Changes in MRI T2 SIR may be related to the severity of the apoptosis in cervical spinal cord.
Animals ; Apoptosis ; physiology ; Cervical Cord ; metabolism ; pathology ; Magnetic Resonance Imaging ; Male ; Rabbits ; Spinal Cord Compression ; metabolism ; pathology
3.Modulation of Pain and Itch by Spinal Glia.
Neuroscience Bulletin 2018;34(1):178-185
Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.
Animals
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Chronic Pain
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pathology
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Humans
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Neuralgia
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metabolism
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Pruritus
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pathology
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Sensory Receptor Cells
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physiology
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Spinal Cord
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pathology
4.Effect of ischemic pretreatment on expression of heat shock protein 70 and injury of spinal cord in canine.
Tao ZHANG ; Zhi-Quan DUAN ; Yu MAO ; Zheng-Ya YU ; Jie LI ; Shi-Jie XIN ; Qiang ZHANG
Chinese Journal of Surgery 2004;42(22):1353-1356
OBJECTIVETo evaluate effect of ischemic pretreatment on expression of heat shock protein 70 (HSP70) and injury of spinal cord in canine.
METHODSFourty-one canine were divided into three groups: the sham-operative group, the pretreatment group and the control group. In the pretreatment group aorta was obstructed for 6 min, and then was opened for 6 min, this procedure was repeated twice, finally aorta was obstructed for 35 min. In the control group aorta was obstructed for 35 min. Nervous function were assessed and HSP70 expression were detected in tissue of spinal cord.
RESULTSIn the pretreatment group, HSP70 expressed in cytoplasm and nucleus at 6, 24 hour after reperfusion, and intensity of HSP70 expression was stronger than that in the control group; The score of nervous function in the pretreatment group was higher than that in the control group. On 7 day after reperfusion the score of nervous function in pretreatment group had no obvious variation, and HSP70 expression was still observed.
CONCLUSIONSIschemic pretreatment can improve ischemic tolerance of spinal cord; HSP70 expression in cytoplasm and nucleus may play a role in ischemic tolerance.
Animals ; Disease Models, Animal ; Dogs ; Female ; HSP70 Heat-Shock Proteins ; metabolism ; physiology ; Ischemic Preconditioning ; Male ; Reperfusion Injury ; prevention & control ; Spinal Cord ; metabolism ; Spinal Cord Injuries ; prevention & control ; Spinal Cord Ischemia ; physiopathology ; prevention & control
5.The effect of formalin-induced pain on CCK in rat spinal cord neurons.
Li LI ; Hong-an LI ; Jin-fang JIANG ; Wei-hua LIANG ; Jun-qiang SI
Chinese Journal of Applied Physiology 2009;25(2):217-220
AIMCCK is one of the strongest endogenous anti-opioid substances and suppresses morphine tolerance which results from long term use of morphine. This study explores the modulatory effect of CCK on pain formalin-induced.
METHODSThe effect of formalin-induced pain on CCK immunoreactivity in rat sensory neurons was observed through immunohistochemistry technique.
RESULTSAfter 1 h of subcutaneous injection of formalin in one paw of rats, the number of positive neurons of CCK immunoreactivity in spinal cord neurons was obviously increased and greater than that of non-injection side (P <0.01). The semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.397 +/- 0.014 and 0.295 +/- 0.007 in injection side and non-injection side respectively, the difference was obvious (P < 0.01). After 3 h of subcutaneous injection of formalin in one paw of rats, the semi-quantitative optical density average values of CCK immunoreactivity neurons were 0.366 +/- 0.009 and 0.303 +/- 0.005 in injection side and noninjection side respectively, the difference was significant (P < 0.01).
CONCLUSIONFormalin-induced pain can significantly change semi-quantitative optical density average value of CCK immunoractivity in spinal cord neurons, this indicates CCK participates in modulation of pain.
Animals ; Cholecystokinin ; metabolism ; physiology ; Female ; Formaldehyde ; Male ; Neurons ; metabolism ; Pain ; chemically induced ; physiopathology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Cholecystokinin ; metabolism ; physiology ; Spinal Cord ; metabolism ; pathology
6.Presence of multiple peripheral circadian oscillators in the tissues controlling voiding function in mice.
Jong Yun NOH ; Dong Hee HAN ; Mi Hee KIM ; Il Gyu KO ; Sung Eun KIM ; Noheon PARK ; Han Kyoung CHOE ; Khae Hawn KIM ; Kyungjin KIM ; Chang Ju KIM ; Sehyung CHO
Experimental & Molecular Medicine 2014;46(3):e81-
Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4-5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1-/- Per2-/- mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function.
Animals
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*Circadian Clocks
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Drinking
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Mice
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Organ Specificity
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Periaqueductal Gray/metabolism/physiology
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Period Circadian Proteins/genetics/*metabolism
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Pons/metabolism/physiology
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Spinal Cord/*metabolism/physiology
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Urinary Bladder/innervation/metabolism/*physiology
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Urination
7.Comparison study of pelvic floor muscle tension and neuropeptide level in different level of spinal cord injury.
Zhen LÜ ; Jian-Jun LI ; Li-Min LIAO ; Yi HONG
Chinese Journal of Surgery 2009;47(12):927-930
OBJECTIVETo find more evidence for mechanism and treatment of pelvic floor dysfunction (PFD), we observed muscle tension and neuropeptide of pelvic floor muscle in rats after spinal cord injury (SCI).
METHODS30 SD adult female rats were randomly divided into suprasacral cord injury group (SS), spinal cord injury at or below the sacral level group (SC) and normal group; 4 weeks after transection of spinal cord, muscle tension including compliance and excitability, and neuropeptide were observed.
RESULTSCompliances in SC group, SS group and normal group were (16.23 +/- 4.46) g, (13.44 +/- 4.15) g and (14.46 +/- 5.61) g respectively, there were no difference among them (P > 0.05), but their excitability under best initial length were (0.35 +/- 0.19) g, (2.80 +/- 2.12) g and (7.75 +/- 2.98) g according to SC, SS and normal group, excitability under prolonged length were (2.61 +/- 0.73) g, (4.67 +/- 1.16) g, (14.86 +/- 3.79) g respectively. SC and SS group were both lower than normal group (P < 0.05), meanwhile SC group was much lower than SS group (P < 0.05); neuropeptide Y and vasoactive intestinal peptide in SS and SC group were significant lower than normal group, and these two neuropeptides in SC were much lower than SS group (P < 0.05).
CONCLUSIONSMuscular excitability and neuropeptide in pelvic floor muscle are decreased obviously at both below and above sacral cord injury, SCI below sacral cord makes much lower level excitability and neuropeptide. The abnormality in pelvic floor muscle after SCI should be emphasized.
Animals ; Disease Models, Animal ; Female ; Muscle Tonus ; physiology ; Neuropeptides ; metabolism ; Pelvic Floor ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism ; physiopathology ; Vasoactive Intestinal Peptide ; metabolism
8.REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4.
Siyue QIN ; Pan YOU ; Hui YU ; Bo SU
Neuroscience Bulletin 2023;39(6):929-946
A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.
Mice
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Animals
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Amyotrophic Lateral Sclerosis/metabolism*
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Superoxide Dismutase-1/metabolism*
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Superoxide Dismutase/metabolism*
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Mice, Transgenic
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Spinal Cord/pathology*
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Mitochondria/physiology*
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Disease Models, Animal
9.Effect of nerve growth factor on neuronal apoptosis after spinal cord injury in rats.
Xiaojian CAO ; Changhua TANG ; Yongxiang LUO
Chinese Journal of Traumatology 2002;5(3):131-135
OBJECTIVETo explore the molecular mechanism of the protective effect of nerve growth factor (NGF) on injured spinal cord.
METHODSThe posterior T(8) (the 8th thoracic segment) spinal cords of 60 Wistar rats were injured by impacts caused by objects (weighing 10 g) falling from a height of 2.5 cm with Allen's way. Solution with nerve growth factors (NGF) was given to 30 rats (the NGF group) through a microtubule inserted into the subarachnoid cavity immediately, and at 2, 4, 8, 12 and 24 hours after spinal cord injury (SCI) respectively. Normal saline (NS) with same volume was given to the other 30 rats (the NS group) with the same method. And 5 normal rats were taken as the normal controls. The expression of bcl-2 and bax proteins in spinal cord was detected with immunohistochemistry. The apoptotic neurons in spinal cord were measured with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling of DNA fragments (TUNEL) staining.
RESULTSThe positive expression of bcl-2 protein was strong in the normal controls, but decreased in the NS group, and increased significantly in the NGF group as compared with that of the NS group (P<0.01). The positive expression of bax protein was also strong in the normal controls, but increased in the NS group, and decreased significantly in the NGF group as compared with that of the NS group (P<0.01). Apoptotic neurons were found in the NS group, and they decreased significantly in the NGF group as compared with that of the NS group (P<0.01).
CONCLUSIONSNGF can protect the injured nerve tissues through stimulating the expression of bcl-2 protein, inhibiting the expression of bax protein and inhibiting the neuronal apoptosis after SCI.
Animals ; Apoptosis ; physiology ; Female ; Immunohistochemistry ; Male ; Nerve Growth Factor ; physiology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; physiopathology
10.Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training.
Qingquan HAN ; Jingjing XIANG ; Yun ZHANG ; Hujun QIAO ; Yongwei SHEN ; Chun ZHANG
Chinese Medical Journal 2014;127(24):4220-4225
BACKGROUNDSpinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.
METHODSSCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma.
RESULTSThe topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.
CONCLUSIONThese observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.
Animals ; Cell Line ; Dependovirus ; genetics ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; physiology ; Humans ; Immunohistochemistry ; Male ; Motor Activity ; genetics ; physiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism