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Nan Sui

Publications and source records attributed to Nan Sui.

7 recordsLinked to original sources

Constipation and Psychiatric Disorders: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies have shown a link between constipation (CN) and psychiatric disorders, including Schizophrenia (SP), Bipolar disorder (BD), Schizoaffective disorder (SD), and Parkinson's disease (PD). However, it is still unknown whether CN affects the occurrence and development of psychiatric disorders or whether psychiatric disorders cause the occurrence and development of CN. Therefore, this study used Mendelian randomization (MR) analysis to evaluate the relationship between CN and psychiatric disorders. METHOD: We used genome-wide association studies (GWAS) to assess the relationship between constipation (N = 411, 623) and four psychiatric disorders, including SP ( N = 77, 096), BD (N = 51, 710), SD ( N = 210, 962), PD (N = 482, 730 ), using bidirectional MR analysis. Inverse variance weighting (IVW), MR Egger (ME) and Weighted median (WM) were used as causal analysis methods. Cochran's Q test, funnel plot, MR Egger intercept test and Leave.one.out analysis were used to detect sensitivity. Confounding factors were analyzed and eliminated by LDtrait to avoid influencing the final MR Analysis result. RESULTS: The results of positive MR analysis indicated that there was no evidence of influence of constipation on SP (OR 1.043, 95%CI 0.946 - 1.149, P value = 0.398), BD (OR 1.114, 95%CI 0.995 - 1.248, P value = 0.062), SD (OR 0.934, 95%CI 0.674 - 1.294, P value = 0.682) and PD (OR 1.118, 95%CI 0.918 - 1.361, P value = 0.269) under gene prediction. Reverse MR analysis suggested that SP (OR 1.030, 95% CI 1.001-1.060, P value = 0.042) had a causal relationship with constipation. BD (OR 0.993, 95% CI 0.962-1.025, P value = 0.664), SD (OR 1.021, 95% CI 0.984-1.059, P value = 0.265) and PD (OR 1.004, 95% CI 0.974-1.035, P value = 0.790) were not associated with CN. CONCLUSION: There was a positive association between SP and CN. CN may have no exact causal relationship with BD, SD and PD, and the interaction mechanism between these diseases needs to be further explored.

Constipation↗

Gene transfer of cocaine hydrolase suppresses cardiovascular responses to cocaine in rats.

We previously found that injection of a cocaine hydrolase (CocE) engineered from human butyrylcholinesterase will transiently accelerate cocaine metabolism in rats while reducing physiological and behavioral responses. To investigate more extended therapeutic effects, CocE cDNA was incorporated into a replication-incompetent type-5 adenoviral vector with a cytomegalovirus promoter. In rats dosed with this agent (2.2 x 10(9) plaque-forming units), the time course of expression was characterized by reverse transcription polymerase chain reaction for CocE mRNA and by radiometric assay for enzyme activity. Liver and plasma showed comparable expression, beginning 2 days after vector administration and peaking between 5 and 7 days. Plasma CocE content was up to 100 mU/ml, with total cocaine hydrolyzing activity 3000-fold greater than in "empty vector" or untreated controls. This level of expression approximated that found immediately after i.v. injection of purified hydrolase, 3 mg/kg, a dose that shortened cocaine halflife and blunted cardiovascular effects. Sucrose density gradient analysis showed that 96% of the circulating CocE activity was associated with tetrameric enzyme forms, expected to be stable in vivo. Consistent with this expectation, CocE from vector-treated rats showed a plasma t(1/2) of 33 h when reinjected into naive rats. Transduction of another mutant butyrylcholinesterase, Applied Molecular Evolution mutant 359 (AME(359)), caused plasma cocaine hydrolase activity to rise 50,000-fold. At the point of peak AME(359) expression, cocaine was cleared from the blood too rapidly for accurate measurement, and pressor responses to the injection of drug were greatly impaired.

Animals↗

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction.

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation (approximately 20%) to synaptic depression (approximately 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Animals↗

Susceptibility to morphine place conditioning: relationship with stress-induced locomotion and novelty-seeking behavior in juvenile and adult rats.

Previous studies demonstrated that the rewarding effect of psychostimulants, such as amphetamine and cocaine, can be predicted by locomotor activity toward novelty in a free-choice situation but not motor response developed in inescapable environment. However, whether this relationship also exists with narcotic morphine remains unclear. In the present study, the relationship between morphine place conditioning and open field as well as novelty-seeking behavior was examined in both juvenile and adult rats. By using arena open field and the same arena containing novel object, we investigated the initial open-field activity and novelty-seeking behavior after familiarization process, respectively, in juvenile and adult rats. Subsequently, the relationship between morphine (2 mg/kg) place conditioning and the above two behaviors was examined. Our results demonstrated that morphine place conditioning effect was readily acquired in both groups. The magnitude of this effect positively correlated with novelty-seeking intensity but not with open-field activity. This is the case whether juvenile or adult group was examined separately or across ages. However, only rats with high response to novelty (NHR) from their respective group expressed significant duration increase in drug-paired compartment. Rats with low response to novelty (NLR) showed no sign of this effect after the same drug training, suggesting slow acquisition of this effect in NLRs. These results also indicated that novelty-seeking actions and the rewarding effect of morphine possessed a common pathway and that neural and hormonal substrates activated in a mild stress environment like in the open field may not be critically involved in this process. The ontogenetic specificity and nonspecificity between different-aged rats as with the above relationship were discussed in this paper.

Age Factors↗

Effects of scopolamine and physostigmine on acquisition of morphine-treated rats in Morris water maze performance.

AIM: To investigate effects of morphine on acquisition process of rats a nd interactions of opioid and cholinergic systems by Morris water maze performance. METHODS: Morris water maze was used to measure the latency of rats with drug s treatment to find the covert platform. RESULTS: Chronic morphine administration (10 mg/kg) impaired the acquisition process of rats in Morris water maze task. Appreciable difference was identified with morphine 10 mg/k g group compared with morphine 3 mg/kg group. Co-administration of morphine (10 mg/kg) and scopolamine (3 mg/kg) aggravated acquisition impairment induced by morphine 1 0 mg/kg or scopolamine alone, though scopolamine itself induced no salient changes in acquisition capabilities of rats. In addition, physostigmine (0.1 mg/kg) could appreciably attenuate morphine-induced acquisition impairment. CONCLUSION: Morphine 10 mg/kg evidently impaired acquisition process of rats. There was a close relationship between the acquisition capabilities of morphine-treated rats and the functions of cholinergic system.

Animals↗