AIMS: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.
METHODS: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16-E18 rats.
RESULTS/OUTCOMES: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.
CONCLUSIONS/INTERPRETATION: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.
AIM OF THE STUDY: To assess the motor and cognitive effects of acute oral administration of CT root methanolic extract and hippocampal long-term plasticity in the CA1 region of the CCH rat model.
MATERIALS AND METHODS: Male Sprague Dawley rats (200-300 g) were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham operation. Then, these rats were given oral administration of CT root extract at doses of 100, 200 or 300 mg/kg on day 28 post-surgery and tested using behavioural tests (open-field test, passive avoidance task, and Morris water maze) and electrophysiological recordings (under urethane anaesthesia).
RESULTS: Treatment with CT root extract at the doses of 200 and 300 mg/kg resulted in a significant enhancement in memory performance in CCH rats induced by PBOCCA. Furthermore, CCH resulted in inhibition of long-term potentiation (LTP) formation in the hippocampus, and CT root extract rescued the LTP impairment. The CT root extract was confirmed to improve the glutamate-induced calcium increase via calcium imaging using primary cultured rat neurons. No significance difference was found in the CaMKII expression. These results demonstrated that CT root extract ameliorates synaptic function, which may contribute to its improving effect on cognitive behaviour.
CONCLUSIONS: Our findings demonstrated an improving effect of CT root extract on memory in the CCH rat model suggesting that CT root extract could be a potential therapeutic strategy to prevent the progression of cognitive deterioration in vascular dementia (VaD) and Alzheimer's disease (AD) patients.
METHOD: A retrospective cross-sectional study was conducted from December 2020 to February 2021 using secondary data from the National Diabetic Registry (NDR), Malaysia, and reviewed patients' diabetic records for the year 2020. All T2DM patients aged >18 years who were registered with the NDR in 2020 and fulfilled the inclusion and exclusion criteria were included in the study. Descriptive statistics and multiple logistic regression analysis were performed. Data were analysed using SPSS version 26.0. A total of 343 samples were included in this study for the determination of the proportion of microalbuminuria and its associated factors.
RESULTS: Of 343 respondents, 34.4% had microalbuminuria. HbAlc >7.0% (AdjOR 2.19, 95% CI: 1.35, 3.55, p=0.001), HDL <1.04 mmol/L (AdjOR 2.44, 95% CI: 1.323, 4.52, p=0.004), dyslipidaemia (AdjOR 1.90, 95% CI: 1.03, 3.48, p=0.039), and peripheral neuropathy (AdjOR 3.01, 95% CI: 1.02, 8.93, p=0.047) were significantly associated with microalbuminuria. Conclusion: Microalbuminuria is a modifiable risk factor in preventing the progression of ESRF among T2DM patients. Therefore, identification of factors associated with microalbuminuria among this high-risk group is important to facilitate early screening and prompt treatment to prevent progression of diabetic kidney disease to ESRF.
OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.
METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).
RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.
CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.
RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.
CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.