Enhancement of neuronal excitability in the medial prefrontal cortex following prenatal morphine exposure.

The clinical use and abuse of opioids during human pregnancy have been widely reported. Several studies have demonstrated that opioids cross the placenta in rats during late gestation, and prenatal morphine exposure has been shown to have negative outcomes in cognitive function. The medial prefrontal cortex (mPFC) is believed to play a crucial role in cognitive processes, motivation, and emotion, integrating neural information from several brain areas and sending converted information to other structures. Dysfunctions in this area have been observed in numerous psychiatric and neurological disorders, including addiction. This current study aimed to compare the electrophysiological properties of mPFC neurons in rat offspring prenatally exposed to morphine. Pregnant rats were injected with morphine or saline twice a day from gestational days 11-18. Whole-cell patch-clamp recordings were performed in male offspring on postnatal days 14-18. All recordings were obtained in current-clamp configuration from mPFC pyramidal neurons to assess their electrophysiological properties. The results revealed that prenatal exposure to morphine shifted the resting membrane potential (RMP) to less negative voltages and increased input resistance and duration of action potentials. However, the amplitude, rise slope, and afterhyperpolarization (AHP) amplitude of the first elicited action potentials were significantly decreased in rats prenatally exposed to morphine. Moreover, the sag voltage ratio was significantly decreased in the prenatal morphine group. Our results suggest that the changes observed in the electrophysiological properties of mPFC neurons indicate an elevation in neuronal excitability following prenatal exposure to morphine.

Acute adolescent morphine exposure improves dark avoidance memory and enhances long-term potentiation of ventral hippocampal CA1 during adulthood in rats.

Adolescence represents a distinctive vulnerable period when exposure to stressful situations including opioid exposure can entail lasting effects on brain and can change neural mechanisms involved in memory formation for drug-associated cues, possibly increasing vulnerability of adolescents to addiction. Herein, the effects of acute adolescent morphine exposure (AAME, two injections of 2.5 mg/kg SC morphine on PND 31) were therefore investigated 6 weeks later (adulthood) on avoidance memory and hippocampal long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in transvers slices from the ventral hippocampus in adult male rats using field recordings technique. Animal body weight was measured from PND 31 throughout PND 40 and also in four time points with 1 week intervals from adolescence to adulthood (PNDs 48, 55, 62 and 69) to evaluate the effect of AAME on the weight gain. We showed that there were no effects on body weight, anxiety-like behaviour and locomotor activity, even until adulthood. There was an improved dark avoidance memory during adulthood. Finally, AAME had no effects on baseline synaptic responses and resulted in a decrease in the mean values of the field excitatory postsynaptic potential slopes required to evoke the half-maximal population spike amplitude and an enhancement of LTP magnitude (%) in the ventral CA1 during adulthood. Briefly, our results suggest long-lasting effects of acute adolescent morphine exposure on the ventral hippocampus, which begin the enhancing of synaptic plasticity and the improving of emotional memory in adulthood.

Relationship of sleep duration and sleep quality with health-related quality of life in patients on hemodialysis in Neyshabur.

Background: As a public health priority, health-related quality of life (HRQoL) is associated with some factors like sleep disorders. Taking this into consideration, this study aimed at investigating the relationship between sleep duration and sleep quality with HRQoL in patients on hemodialysis. Methods: This cross-sectional study was carried out among 176 patients on hemodialysis who were admitted to the dialysis ward of 22 Bahman hospital and a private renal clinic in Neyshabur (a city in North-East of Iran) in 2021. Sleep duration and quality were measured using an Iranian version of Pittsburgh Sleep Quality Index (PSQI) and HRQoL was evaluated with the Iranian version of a 12-Item Short Form Survey (SF-12). To analyze the data and examine the independent association of sleep duration and quality with HRQoL, multiple linear regression model was performed. Results: The mean age of the participants was 51.6 ± 16.4 and 63.6% were male. Moreover, 55.1% and 5.7% of subjects reported a sleep duration shorter than 7 h and equal to or more than 9 h, respectively, and the value prevalence of poor sleep quality was reported as 78.2%. Furthermore, the reported overall score of HRQoL was 57.6 ± 17.9. According to the adjusted models, poor sleep quality was negatively associated with the total HRQoL score (B = -14.5, P < 0.001). Shedding light on sleep duration and Physical Component Summary (PCS), the result indicated that insufficient sleep duration (<7 h) had a borderline negative association with PCS (B = -5.96, p = 0.049). Conclusions: Sleep duration and quality have important effects on HRQoL in patients on hemodialysis. Therefore, in line with improving sleep quality and HRQoL among these patients, essential interventions should be planned and performed.

Adolescent morphine exposure impairs dark avoidance memory and synaptic potentiation of ventral hippocampal CA1 during adulthood in rats.

Adolescence is a neurobiological critical period for neurodevelopmental processes. Adolescent opioid exposure can affect cognitive abilities via regional-specific lasting changes in brain structure and function. The current study was therefore designed to assess the long-term effects of adolescent morphine exposure on dark avoidance memory and synaptic plasticity of the ventral hippocampal CA1. Adolescent Wistar rats received escalating doses of morphine for 10 days. Morphine injections were started with an incremental dose of 2.5 mg/kg to reach a dose of 25 mg/kg. 30 days after the last injection, inhibitory memory and in vitro field potential recording were evaluated. Also, the weight of the animals was measured during drug and post-drug exposure. We found that adolescent morphine exposure decreased weight gain during morphine and post-morphine exposure. Passive avoidance memory was impaired in the morphine group. Moreover, adolescent morphine exposure caused an increase in baseline synaptic responsiveness and failed long-term potentiation (LTP) in the ventral hippocampal CA1 during adulthood. In the morphine group, the mean values of the field excitatory postsynaptic potential (fEPSP) slopes required to elicit a half-maximal population spike (PS) amplitude were significantly greater than that of the saline group. Therefore, adolescent morphine exposure has a durable effect on memory functions, synaptic activity, and plasticity of ventral hippocampal CA1. Adults with adolescent morphine exposures may experience maladaptive behaviors and cognitive disabilities.

The Protective Effects of Crocin on Input-Output Functions and Long-term Potentiation of Hippocampal CA1 Area in Rats Exposed to Chronic Social Isolated Stress.

Introduction: The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress. Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups. Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex. Highlights: Neuronal excitability and long-term plasticity of CA1 were impaired by chronic isolation stress.The memory was protected by low and particularly high doses of crocin in the chronic isolation stress condition.Crocin decreased the corticosterone levels in hippocampus, but not frontal cortex. Plain Language Summary: The lack of social communication (isolation stress) is associated with the primary risk of brain functions. On the other hand, crocin as one of effective components of saffron is helpful for improvement of memory. Therefore, the protective effect of two doses of crocin on cellular mechanism of memory in rats exposed to chronic social isolated stress was investigated in present study. Chronic isolation stress (CIS) was induced 6h/day, and crocin was administrated for a period of 21 days at two doses of 30 and 60 mg/kg. The electrophysiological and cellular mechanism of memory in the CA1 area of the hippocampus were investigated. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. It was concluded that the chronic isolation stress impaired neural excitability and long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. Also, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups.

Development of anxiety-like behaviors during adolescence: Persistent effects of adolescent morphine exposure in male rats.

Epidemiological studies show the prevalence of opioid use, misuse and abuse in adolescents, which imposes social and economic accountability worldwide. Chronic opioid exposure, especially in adolescents, may have lasting effects on emotional behaviors that persist into adulthood. The current experiments were therefore designed to study the effects of sustained opioid exposure during adolescence on anxiety-like behaviors. Adolescent male Wistar rats underwent increasing doses of morphine for 10 days (PNDs 31-40). After that the open field test (OFT) and elevated plus maze (EPM) test were performed over a 4-week postmorphine treatment from adolescence to adulthood. Moreover, the weight of the animals was measured at these time points. We found that chronic adolescent morphine exposure reduces the weight gain during the period of morphine treatment and 4 weeks after that. It had no significant effect on the locomotor activity in the animals. Moreover, anxiolytic-like behavior was observed in the rats exposed to morphine during adolescence evaluated by OFT and EPM test. Thus, long-term exposure to morphine during adolescence has the profound potential of altering the anxiety-like behavior profile in the period from adolescence to adulthood. The maturation of the nervous system can be affected by drug abuse during the developmental window of adolescence and these effects may lead to behaviorally stable alterations.

Impairment of spatial memory and dorsal hippocampal synaptic plasticity in adulthood due to adolescent morphine exposure.

Opioid exposure during adolescence, a crucial period of neurodevelopment, has lasting neurological and behavioral consequences and affects the cognitive functions in adulthood. This study investigated the effects of adolescent morphine exposure in spatial learning and memory and synaptic plasticity of the CA1 area of the dorsal hippocampus. Adolescent Wistar rats received increasing doses of morphine for 1, 5, and 10 days. Acute morphine group was injected 2.5 mg/kg morphine for 1 day, subchronic morphine group for 5 days, with an increasing dose of 2.5 mg/kg and reached to the dose of 12.5 mg/kg and chronic morphine group for 10 days that began with an increasing dose of 2.5 mg/kg and reached to the dose of 25 mg/kg. Then after 25 days and reaching adulthood, spatial learning and memory were evaluated via the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of dorsal hippocampal plasticity in adult rats by in vitro field potential recordings. Subchronic and chronic adolescent morphine exposure impaired spatial learning and memory in the MWM test. Baseline synaptic responses in the chronic morphine group were increased and long-term potentiation (LTP) impaired in the CA1 area in subchronic and chronic morphine groups. In adulthood, the slope of the field excitatory postsynaptic potential (fEPSP) required to elicit a half-maximal population spike (PS) amplitude was significantly larger in subchronic and chronic adolescent morphine exposure compared to the saline group. Therefore, subchronic and chronic adolescent morphine exposure altered synaptic transmission and plasticity in addition to learning and memory. Long-term morphine exposure during adolescence can interfere with neurodevelopment, making a persistent impression on plasticity and cognitive capability in adulthood.

Bond strength and microleakage of different types of cements in stainless steel crown of primary molar teeth.

BACKGROUND: The margin of crown is a significant area for plaque accumulations. Therefore, the ability of the cement to seal the margin is very important. The aim of the present study was to evaluate the bond (retentive) strength, microleakage, and failure mode of four different types of cements in stainless steel crown (SSC) of primary molar teeth. MATERIALS AND METHODS: In this experimental study, eighty extracted primary molar teeth were divided into two groups of forty teeth to test the microleakage and bond strength. The crowns were cemented according to the manufacturer guidelines with four cement types including self-cure glass ionomer, resin-modified glass ionomer, polycarboxylate, and resin cements. Stereomicroscope and universal testing machine were used to measure the microleakage and bond strength, respectively. For calculating the surface area of crowns, three-dimensional scanning was used. Furthermore, the failure mode was examined after the bond strength test. The cements surfaces and the tooth-cement interfaces were evaluated using scanning electron microscopy (SEM). The obtained values were analyzed using SPSS-23 software through Shapiro-Wilk and one-way analysis of variance tests. Means, standard deviations, medians, and interquartile ranges were calculated. P < 0.05 was considered as statistically significant in all analyses. RESULTS: Significant differences between microleakage (P = 0.001) and failure mode (P = 0.041) of the four types of cements were obtained. However, the mean bond strengths of the four groups did not differ significantly (P = 0.124). The obtained SEM images confirmed the results of bond strength and microleakage. CONCLUSION: Resin cement and resin-modified glass ionomer, respectively, showed superior properties and are recommended for use in SSCs of primary molar teeth.

Effects of Levothyroxine on Visual Evoked Potential Impairment Following Local Injections of Lysolecithin into the Rat Optic Chiasm.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system which has no any known definitive treatment. Studies have shown that thyroid hormones (THs) in addition to their roles in the development of the nervous system and the production of myelin have important roles in the adult's brain function. Since the only way to treat MS is the restoration of myelin, the aim of this study was to evaluate the effects of levothyroxine on visual evoked potential (VEP) impairment following local injections of lysolecithin into the rat optic chiasm. METHODS: To induce demyelination, lysolecithin was injected into the optic chiasm of male Wistar rats. VEP recording was used to evaluate demyelination and remyelination before and 10, 17, and 24 days after the lysolecithin injection. The rats received an intraperitoneal injection of levothyroxine with doses 20, 50, and 100 µg/kg in different experimental groups. RESULTS: VEP latency and amplitude showed demyelination at 10 and 17 days after an induced lesion in MS group which was reversed at day 24. Levothyroxine prevented these impairments, especially in high doses. CONCLUSIONS: According to the results, lysolecithin-induced demyelination at optic chiasm and VEP impairments can be restored by administration of levothyroxine. Therefore, THs probably have positive effects in demyelinating diseases.

The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon-gamma in Rat Model of Multiple Sclerosis.

BACKGROUND: There is an increase in inflammatory and a reduction in anti-inflammatory cytokines in multiple sclerosis (MS). Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin-10 (IL-10) and interferon gamma (IFN-γ) in animal models of MS. MATERIALS AND METHODS: To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 µg/kg) for 21 days. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay at 7, 14, and 21 days after that. RESULTS: The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL-10 compared to the sham group (P < 0.05) at 7th day, but this increase was prevented by all doses of levothyroxine. IFN-γ was decreased significantly (P < 0.001) 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN-γ significantly. CONCLUSION: The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses.

Constrained tracking control for nonlinear systems.

This paper proposes a tracking control strategy for nonlinear systems without needing a prior knowledge of the reference trajectory. The proposed method consists of a set of local controllers with appropriate overlaps in their stability regions and an on-line switching strategy which implements these controllers and uses some augmented intermediate controllers to ensure steering the system states to the desired set points without needing to redesign the controller for each value of set point changes. The proposed approach provides smooth transient responses despite switching among the local controllers. It should be mentioned that the stability regions of the proposed controllers could be estimated off-line for a range of set-point changes. The efficiencies of the proposed algorithm are illustrated via two example simulations.

Effect of Aqueous Extract of Crocus sativus L. on Morphine-Induced Memory Impairment.

In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1) control, (2) morphine which received morphine before the training in the passive avoidance test, (3-5) three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7) the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P < 0.01). Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P < 0.05 and P < 0.01). Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P < 0.01). The results revealed that the saffron extract attenuated morphine-induced memory impairment.