Histone deacetylases are involved in many biological processes and have roles in regulating cell behaviors such as cell cycle entry, cell proliferation and apoptosis. However, the effect of histone deacetylases on the development of hair cells (HCs) has not been fully elucidated. In this study, we examined the influence of histone deacetylases on the early development of neuromasts in the lateral line of zebrafish. Hair cell development was evaluated by fluorescent immunostaining in the absence or presence of histone deacetylase inhibitors. Our results suggested that pharmacological inhibition of histone deacetylases with inhibitors, including trichostatin A, valproic acid and MS-275, reduced the numbers of both HCs and supporting cells in neuromasts. We also found that the treatment of zebrafish larvae with inhibitors caused accumulation of histone acetylation and suppressed proliferation of neuromast cells. Real-time PCR results showed that the expression of both p21 and p27 mRNA was increased following trichostatin A treatment and the increase in p53 mRNA was modest under the same conditions. However, the expression of p53 mRNA was significantly increased by treatment with a high concentration of trichostatin A. A high concentration of trichostatin A also led to increased cell death in neuromasts as detected in a TUNEL assay. Moreover, the nuclei of most of these pyknotic cells were immunohistochemically positive for cleaved caspase-3. These results suggest that histone deacetylase activity is involved in lateral line development in the zebrafish and might have a role in neuromast formation by altering cell proliferation through the expression of cell cycle regulatory proteins.
Animals ; Apoptosis ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism ; Histone Deacetylase Inhibitors/*pharmacology ; Histone Deacetylases/*metabolism ; Histones/metabolism ; Larva/growth & development/metabolism ; Lateral Line System/cytology/*growth & development/metabolism ; Mechanoreceptors/drug effects/*metabolism/physiology ; RNA, Messenger/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/*metabolism

OBJECTIVETo investigate the density and distribution of nerve endings and neuropeptide Y (NPY) in lumbar facet joints of patients with low back pain.

METHODSFifteen patients without low back pain were selected as control group (group A). Facet joint samples in group A were obtained during the operation or lumbar spinal canal tumor they suffered from. Those patients with low back pain were divided into three groups according to their different origins of pain, such as not from facet joint (group B, 15 patients) ,from facet joint only (group C, 20 patients), or from facet joint partially (group D, 20 patients). Different origins were determined by VAS after facet joint block. The density and distribution of nerve ending and neuropeptide in the capsular tissues were analyzed by a modified gold chloride staining and immunochemistry respectively.

RESULTSCompared with the ones in group A and B, the fact joints in group C and D were more inclined to be degenerated and got more nerve endings. NPY was expressed mainly in the facet joint of patients with low back pain in group C and D. In addition, there was a significant relationship between the distribution of nerve endings and NPY expression,while none of them were related with MRI Fujiwara grade of facet joint.

CONCLUSIONThese results suggest that the number of mechanoreceptors, neural sprouting and secreted peptides in the facet joint capsules vary with the change of mechanical or nociceptive stimulation, which may promote the development of low back pain in return.

Adult ; Aged ; Case-Control Studies ; Chronic Pain ; etiology ; metabolism ; pathology ; Female ; Humans ; Low Back Pain ; etiology ; metabolism ; pathology ; Male ; Mechanoreceptors ; physiology ; Middle Aged ; Nerve Endings ; pathology ; Neuropeptide Y ; analysis

PURPOSE: We investigated the effects of group III mechanoreceptors to cardiovascular responses in both pre-menopausal woman and post-menopausal woman during passive ankle dorsiflexion (PAD). METHODS: Twenty healthy volunteers (10 post-menopausal women and 10 pre-menopausal women) were recruited for this study. Stroke volume (SV), heart rate (HR), cardiac output (CO), and total vascular conductances (TVC) were measured continuously throughout the experiment. To stimulate the group III mechanoreceptors, PAD was performed for one minute. RESULTS: The results showed that mean arterial pressure (MAP) mediated by the mechanoreflex activation was significantly increased in both groups. However, this pressor response was significantly higher in post-menopausal women. This reflex significantly increased both SV and CO in pre-menopausal women, while there were no differences in post-menopausal women. There was no difference in HR in either group. The mechanoreflex significantly decreased TVC in post-menopausal woman, while there was no difference in pre-menopausal woman. CONCLUSION: The results indicate that the excessive pressor response mediated by the mechanoreflex occurs due to overactivity of group III mechanorecptors and the mechanism is produced mainly via peripheral vasoconstriction in post-menopausal women.
Aged ; Blood Pressure ; Body Mass Index ; Cardiac Output ; Estrogens/*metabolism ; Female ; Heart Rate ; Humans ; Mechanoreceptors ; Middle Aged ; Postmenopause ; Premenopause ; Reflex, Stretch/*physiology ; Stroke Volume

OBJECTIVETo investigate the role of activated brain regions in Parkinson's disease (PD) during tactile stimulation.

METHODSTwenty-one patients with early PD[mean age (60.43 +/-9.65)y] and twenty-two age-matched healthy controls [mean age (59.23 +/-11.12)y] were enrolled in the study. All the patients were tested by the United Parkinson Disease Rating Scale (UPDRS) as the evaluation of the disease severity. A block design was used when the finger tactile stimulation was given to the subjects. The hypoactive and hyperactive regions of PD patients were confirmed first, which were identified as regions of interest (ROI). ROI analysis was performed to quantify BOLD signal changes when subjects were under tactile stimulation. The correlations of signal changes with disease severity, and correlations of hyperactive with hypoactive regions were analyzed.

RESULTSRight primary sensory and motor cortex, right supplementary motor area (SMA), bilateral caudates, bilateral precuneus, bilateral occipital visual cortex and left middle temporal gyrus were hypoactivated in PD, while right prefrontal cortex (PFC) and right caudate were hyperactivated. The hypoactivation of right SMA was negatively correlated with disease severity. All the hypoactive and hyperactive regions were positively correlated with activation of caudates. There was a positive correlation between hyperactive PFC and hypoactive regions.

CONCLUSIONSThe signal change of SMA is directly related to disease severity in early PD, and caudates may play a significant role in PD tactile processing. The hyperactivation of PFC may be not a compensation but a pathophysiological change related to PD neural dysfunction.

Aged ; Brain ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mechanoreceptors ; physiology ; Middle Aged ; Parkinson Disease ; physiopathology ; Severity of Illness Index ; Time Factors ; Touch ; physiology ; Touch Perception ; physiology

This study sought to elucidate the effect of mechanical strain on the differentiation of mesenchymal stem cells into osteoblasts. Under the conditons of inducing osteoblasts, Immunohistochemical methods and RT-PCR technology were applied in osteogenic supplements medium to detect: (1) the expression of Alkaline phosphatase (ALP), Type I collagen (COL I ), Osterx (Osx) and Osteocalcin (OCN) mRNA, with cyclic strain (3%, 0.5 Hz) applied for 15 min, 30 min, 1 h, 2 h, 4 h, 3 d, 7 d, 14 d; (2) the expression of Osx mRNA and OCN mRNA with 3% strain for 1 h. The results showed: (1) ALP mRNA expression was higher at 7 days; COL I mRNA expression was greater obviously at 7 days and 14 days than that at 3 days and that of the unstrained cells; (2) the expression of Osx mRNA was up-regulated after 15min by strain stimulation,which was significantly increased at 30 min and 1 h in the unstrained cells. The expression of OCN mRNA was not affected in the unstrained cells at 15 min, whereas strain could promote the expression of OCN mRNA at this period. The expression of OCN mRNA was more obviously upregulated in the strained cells at 30 min and 1 h when compared with that in the unstrained cells; (3) the strain (1% and 3%) significantly promoted the expression of Osx mRNA; 10% strain had a little effect on Osx mRNA expression. The expression of OCN mRNA was up-regulated by 3% strain, whereas it had little effect at 1% and 10% strain. In summary, mechanical strain can promote the differentiation of mesenchymal stem cells into osteoblasts.
Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Mechanoreceptors ; physiology ; Mechanotransduction, Cellular ; physiology ; Mesenchymal Stromal Cells ; cytology ; Mice ; Osteoblasts ; cytology ; Osteocalcin ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Sp7 Transcription Factor ; Stress, Mechanical ; Transcription Factors ; genetics ; metabolism

AIMTo observe the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, and to investigate its possible mechanisms.

METHODSStretch (120 mmHg, 50 ms) was applied in the end of action potential by the pressure-clamp technique to observe if there would be any changes in rabbit cardiac activity and streptomycin (500 micromol/L) was used to identify the mechanism.

RESULTSStretch in the end of action potential caused arrhythmia (P < 0.05) and streptomycin blocked the above effect (P < 0.05).

CONCLUSIONStreptomycin could block the effect of stretching left ventricles in the end of action potential on rabbit cardiac activity, which indicates that stretch-activated ion channels involve it.

Action Potentials ; physiology ; Animals ; Arrhythmias, Cardiac ; etiology ; physiopathology ; Female ; Heart Ventricles ; physiopathology ; In Vitro Techniques ; Ion Channels ; physiology ; Male ; Mechanoreceptors ; drug effects ; Proprioception ; Rabbits ; Streptomycin ; pharmacology

PURPOSE: The purpose of this study was to investigate the activation of the respiratory centers during insufflation of the larynx with CO2 at different flow rates and concentrations. MATERIALS AND METHODS: The experiments were carried out in spontaneous air breathing rabbits, anesthetized with thiopental sodium (25mg kg(-1) i.v.). The larynx was separated from the oropharyngeal cavity and the trachea. The tidal volume (VT) and respiratory frequency (f min(-1)) were recorded from the lower tracheal cannula. The respiratory minute volume (VE) was calculated, the action potentials from the right phrenic nerve were recorded and the inspiratory (TI) and expiratory (TE) periods and the mean inspiratory flow rate (VT/TI) were calculated. The larynx was insufflated at flow rates of 500mL min(-1) and 750mL min(-1), with 7 and 12% CO2-Air by means of a respiratory pump. RESULTS: Insufflation of the larynx, with both gas mixtures, decreased the f and VT significantly. The TI and TE were found to increase significantly due to the decreasing in f. There was a significant decrease in VT/TI ratio. Following bilateral midcervical vagotomy, on the passing of both gas mixtures, significant decreases were observed in the VT, and the responses of f, TI and TE were abolished. After cutting the superior laryngeal nerve, the responses of the VT to both gas mixtures were abolished. CONCLUSION: In conclusion, the results of this study purpose that the stimulation of the laryngeal mechanoreceptors by the effect of hyper- capnia decreases the activation of the respiratory center
Air ; Animals ; Carbon Dioxide/chemistry/*pharmacology ; Female ; Laryngeal Nerves/drug effects/physiology ; Male ; Mechanoreceptors/drug effects/physiology ; Rabbits ; Reflex/*drug effects/physiology ; *Respiratory Mechanics/drug effects ; Tidal Volume

OBJECTIVETo explore the regeneration of mechanical sensory fibers after free nerve transplantation.

METHODNeuroelectrophysiological technique (single nerve fiber recording) was used to test the regeneration rate of mechanical sensory fibers, the proportion of rapidly and slowly adapting receptors, the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers. The regeneration pattern of the mechanoreceptors after free nerve transplantation to the rabbit reconstructed penis was also analyzed.

RESULTS9 months after operation, the number of regenerated mechanical sensory fiber was almost normal. The regenerated rapidly adapting receptors had a higher proportion with higher mature degree than the regenerated slowly adapting receptors. 9 months after nerve transplantation the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers remained below normal.

CONCLUSIONAfter free nerve transplantation to the rabbit reconstructed penis, the function of both rapidly and slowly adapting sensory nerve fiber partially recovered, but in different extent.

Animals ; Ganglia, Sensory ; physiology ; Male ; Mechanoreceptors ; physiology ; Nerve Fibers ; transplantation ; Nerve Regeneration ; Penis ; surgery ; Rabbits

Intraganglionic laminar endings (IGLEs) have been supposed to be the mechanoreceptors in the gut by electrophysiological recording techniques. But the specialized morphology of IGLEs could not be displayed closely associated with this function and the mechanism that IGLEs act as the mechanotransduction sites in the gut is not yet well understood. In the present study, we used styryl dye FM1-43 combined with stretch stimulation in the guinea pig esophagus to test whether IGLEs acted as the mechano-sensitive receptors of the vagal afferent nerves. At the same time, the special structure of IGLEs displayed by FM1-43 was further confirmed by neurobiotin anterograde labeling technique. To further investigate the characteristics of IGLEs as mechanosensitive receptors, different drugs were used to block or stimulate IGLEs activation. Our results indicated that only in the stretched preparation could FM1-43 enter the IGLEs and completely display their specialized structure, which was consistent with that shown by neurobiotin. The amount of IGLEs shown by stretch-evoked FM1-43 staining was much more than that shown without stretch stimulation [(90.4 +/- 9.5) % vs (10.7 +/- 2.1) %, P<0.05]. Ca(2+), TTX (0.6 mumol/L), atropine (0.6 mumol/L), SKF (50 mumol/L), and gadolium (100 mumol/L) had no effect on the IGLEs activation. But for benzamil (100 mumol/L), an epithelial sodium channel blocker, activation of IGLEs by stretch stimulation was significantly blocked. The potent ATP analogue, alpha,beta-methylene ATP (100 mumol/L) could not activate FM1-43 staining without stretch. These results indicate that IGLEs are sensitive to mechanical stimulation. This could lead to the deduction that IGLEs act as the mechanoreceptors of vagal afferent nerve. IGLEs could transmit mechanical stimuli directly through ion channels, independent of neurotransmitter release and action potential propagation. The stretch-sensitive channels on IGLEs probably belong to the epithelial sodium channel family rather than voltage-gated sodium ion channels. Furthermore, styryl dye FM1-43 is a useful activity-dependent marker to demonstrate the structure and function of IGLEs in guinea pig esophagus.
Afferent Pathways ; physiology ; Animals ; Esophagus ; innervation ; Female ; Ganglia, Autonomic ; physiology ; Guinea Pigs ; Male ; Mechanoreceptors ; physiology ; Nerve Endings ; physiology ; Vagus Nerve ; physiology

Swallowing is a rare cause of neurally mediated syncope. The mechanism of swallow syncope that contributes to hypotension, bradycardia, or to both is complex. A 59-year-old man had experienced a recurrent loss of consciousness during swallowing of carbonated beverages or sticky foods. Another 59-year-old man had complained of intermittent syncope just after eating foods. These two patients had no significant structural or functional abnormalities in the esophagus or heart. Both cases showed bradycardia when the lower esophagus was stretched by balloon inflation. The activation of mechanoreceptors in the lower esophagus can be regarded as an initiating factor of these cardioinhibitions. The patients were treated with permanent pacemaker implantation and instructed to change eating habits, respectively.
Bradycardia/etiology ; Deglutition/*physiology ; Esophagus/*innervation ; Humans ; Male ; Mechanoreceptors/*physiology ; Middle Aged ; Syncope/*etiology