Effects and pathophysiological significance of intestinal flora on the enteric neuro-endocrine-immune system / 生理学报

Interactions among the nervous, the endocrine and the immune systems enable the gut to respond to the dietary products, pathogens and microbiota, which maintains the homeostasis of the body. However, dysbiosis may induce or aggravate the gastrointestinal (GI) and extra-GI diseases through changing the activities of enteric nervous system (ENS), enteroendocrine cells and enteric immune cells. Here we review recent advances in the understandings on how intestinal flora may impact the enteric neuro-endocrine-immune system in the gut, thereby contributing to the regulation of pathophysiological processes.

Perinatal antibiotics exposure causes increase in serum 5-hydroxytryptamine level as well as changes in behavior and gastrointestinal motility in the male offspring in mice / 生理学报

The current study was aimed to investigate the potential effects of perinatal exposure to therapeutic dose of penicillin and cefixime on the cognitive behaviors, gastrointestinal (GI) motility and serum 5-hydroxytryptamine (5-HT) level in the offspring. Pregnant rats were continuously treated with cefixime or penicillin in the period between 1 week before and 1 week after labor. Behavior tests, including social preference, self-grooming and elevated plus maze tests, and intestinal motility tests were carried out on the offspring at age of 4 to 10 weeks. Serum 5-HT levels were detected with ELISA, and potassium/sodium hyperpolarization activated cyclic nucleotide-gated channel 2 (HCN2) and tryptophan hydroxylase 1 (TPH1) expression levels in colon epithelium of offspring were detected by Western blot and RT-qPCR. The results showed that, compared with the naive group, cefixime increased social behavior in the female offspring, but did not affect the male offspring. Compared with the naive group, cefixime significantly decreased colonic and intestinal transits, and increased cecum net weight and standardized cecum net weight in the male offspring, but did not affect the female offspring. The serum 5-HT levels in the male offspring, rather than the female offspring, in cefixime and penicillin groups were significantly increased compared with that in the naive group. The protein expression level of HCN2 in colon epithelium of the offspring in cefixime group was significantly down-regulated, and the TPH1 expression level was not significantly changed, compared with that in the naive group. These results suggest that perinatal antibiotics exposure may affect neural development and GI functions of the offspring, and the mechanism may involve peripheral 5-HT and gender-dependent factor.

Intradermal administration of formalin to the cheek induces itch as well as pain behaviors in rats / 上海交通大学学报（医学版）

Objective· Formalin is a classic and most widely used algogenic substance,but its itchy effect is not clear.The present study aims to explore the hypothesis that formalin may induce itch as well as pain.Methods· Flinching,as well as licking and forelimb wiping of the site of injection were counted as pain responses,whereas biting and hind paw scratching of the cheek were counted as itchy responses.To discriminate formalin-induced sensations in rats,the irritant (saline as control) was injected,and then pain and itchy responses were recorded.Results · Intraplantar injection of formalin elicited biphasic behavior responses characterized as flinching,as well as biting or licking of the hind paw without significant gender differences.Following intradermal administration of formalin to the cheek,rats exhibited episodic forelimb wiping of the cheek,representative of pain.No gender difference was noticed for this type of behavior.In addition,episodes of hind paw scratches of the cheek,representative of pruritoceptive responses,also occurred.Interestingly,hind paw scratches appeared to be more pronounced in male than in female rats.Conclusion · Intradermal administration of formalin elicits pruritoceptive as well as nociceptive responses in rats.

Stress-related arterial hypertension in Gper-deficient rats / 生理学报

Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERβ and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.

Upregulation of P2X3 receptors in dorsal root ganglion of TRPV1 knockout female mice / 生理学报

The study was aimed to investigate the changes in mechanical pain threshold in the condition of chronic inflammatory pain after transient receptor potential vanilloid 1 (TRPV1) gene was knockout. Hind-paw intraplantar injection of complete freund's adjuvant (CFA, 20 μL) produced peripheral inflammation in wild-type and TRPV1 knockout female mice. The mechanical pain thresholds were measured during the 8 days after injection and pre-injection by using Von-Frey hair. Nine days after injection, mice were killed and the differences of expression of c-Fos and P2X3 receptor in the dorsal root ganglia (DRG) and spinal cord dorsal horn were examined by Western blotting between the two groups. Compared with that in wild-type mice, the mechanical pain threshold was increased significantly in TRPV1 knockout mice (P < 0.05); 3 days after CFA injection, the baseline mechanical pain threshold in the TRPV1 knockout mice group was significantly higher than that in the wild-type mice group (P < 0.05); The result of Western blotting showed that the expression of c-Fos protein both in DRG and spinal cord dorsal horn of TRPV1 knockout mice group was decreased significantly compared with that in wild-type mice group (P < 0.01, P < 0.05), while the expression of P2X3 receptor in DRG of TRPV1 knockout mice group was increased significantly compared with that in wild-type mice group (P < 0.05). Our findings indicate that TRPV1 may influence the peripheral mechanical pain threshold by mediating the expression of c-Fos protein both in DRG and spinal cord dorsal horn and changing the expression of P2X3 receptor in DRG.

Roles of ACh receptors in the effects of corticosterone on presympathetic neurons in the ventrolateral medulla of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the roles of acetylcholine (ACh) receptors in the rapid effects of corticosterone (CORT) on the presympathetic neurons in the rostral ventrolateral medulla (RVLM) of rats, and study the non-genomic mechanism of glucocorticoid (GC) in the integration of sympathetic cardiovascular activity.</p><p><b>METHODS</b>The effects of microelectrophoresis of CORT on the discharge of the presympathetic neurons in the RVLM were observed by extracellular recording in urethane-anaesthetized rats. The responses of atropine (a blocker for M type of ACh receptor, ATR), d-tubocurarine (a blocker for N1 type of ACh receptor, d-TC) and hexamethonium (a blocker for N2 type of ACh receptor, C6) to the effects of CORT on the presympathetic neurons were investigated respectively.</p><p><b>RESULTS</b>Totally 33 presympathetic neurons in the RVLM were recorded. Among them the firing rate of 25 (76%) presympathetic neurons was increased by microelectrophoresis of CORT. The effects of CORT were also positively correlated with the currents. In the other 8 presympathetic neurons, had was shown no effect after microelectrophoresis of CORT. In 10 presympathetic neurons, which discharge was increased by CORT, microelectrophoresis of ATR decreased the firing rate of these presympathetic neurons (P < 0.05), and did not fully block the excitatory effect induced by CORT. In both 7 and 6 presympathetic neurons, application of d-TC and C6 had no effect on these neurons respectively, and did not fully block the excitatory effect induced by CORT.</p><p><b>CONCLUSION</b>CORT had rapid excitatory effects on the presympathetic neurons in the RVLM, which effect might be independent on ACh receptors.</p>

Changes of motor evoked potentials after spinal cord injuries in rats / 中国应用生理学杂志

<p><b>AIM</b>Study on the relationship between the degraded spinal cord injuries and the changes of the motor evoked potentials (MEP) to prove the diagnosis and prognosis value of MEP.</p><p><b>METHODS</b>After injury at T8-T9 cord using modified Allen's weight-drop method, 27 male SD rats were divided randomly into control group (n = 5), group A (50 gcf, n = 8), group B (70 gcf, n = 8) and group C (100 gcf, n = 6). MEPs elicited by monopolar transcortical stimulation were recorded continuously before injury, just after injury, 15 minutes, 1 hour, 3 hours and 6 hours after injury. The rate of the size of the bleeding or necrosis area to the total cord was also calculated.</p><p><b>RESULTS</b>MEP had no significant change in the control group. The amplitude of MEP's early components in group A or group B decreased or even obliterated after SCI, and then partially recovered, while the late components were lost without any recovery signals. All animals in group C showed no MEP waves excepting 2 rats had recovery signals. The size of the cord injuries area increased according to the dropping force and was correlated significantly with the amplitude of the largest peaks of scMEP 1 hour after SCI (r = -0.821).</p><p><b>CONCLUSION</b>The scMEP changes after SCI are correlated with the injury forces and the pathological changes in the cord, which indicates that scMEP can be used as an objective index for the cord functional monitoring.</p>

Effect of intravenous injection of corticosterone on the presympathetic neurons in rostral ventrolateral medulla of rats / 第二军医大学学报

Objective: To study the role of glucocorticoid i n the integration of sympathetic nervous system and cardiovascular activity. Methods: Neurons in the rostral ventrolateral medulla (RVLM) were extracelluarly recorded and identified as the presympathetic neurons of adult rats. The spontaneous discharge of the presympathetic neurons in the RVLM were observed by bolus intravenous injection of corticosterone (50, 100, 150 μg/kg） . Results: The firing rate of 12 presympathetic neurons was incr eased by intravenous application of corticosterone (P<0.05), and this effect showed a dose-dependent manner. The latency of excitatory effect was (104±2 5) s. Conclusion: Corticosterone can rapidly excite the presym pathetic neurons in the RVLM, this action might be involved in the integration o f sympathetic nervous system through the “rapid membrane effects”.

Effect of intravenous injection of corticosterone on the presympathetic neurons in rostral ventrolateral medulla of rats / 第二军医大学学报

Objective: To study the role of glucocorticoid i n the integration of sympathetic nervous system and cardiovascular activity. Methods: Neurons in the rostral ventrolateral medulla (RVLM) were extracelluarly recorded and identified as the presympathetic neurons of adult rats. The spontaneous discharge of the presympathetic neurons in the RVLM were observed by bolus intravenous injection of corticosterone (50, 100, 150 μg/kg） . Results: The firing rate of 12 presympathetic neurons was incr eased by intravenous application of corticosterone (P<0.05), and this effect showed a dose-dependent manner. The latency of excitatory effect was (104±2 5) s. Conclusion: Corticosterone can rapidly excite the presym pathetic neurons in the RVLM, this action might be involved in the integration o f sympathetic nervous system through the “rapid membrane effects”.