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Introduction: Coronavirus-2019 (COVID-19) spreads rapidly worldwide and causes severe acute respiratory syndrome. The current study aims to evaluate the relationship between the whole-brain functional connections in a resting state and cognitive impairments in patients with COVID-19 compared to the healthy control group., Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) and Montreal cognitive assessment (MoCA) data were obtained from 29 patients of the acute stage of COVID-19 on the third day of admission and 20 healthy controls. Cross-correlation of the mean resting-state signals was determined in the voxels of 23 independent components (IC) of brain neural circuits. To assess cognitive function and neuropsychological status, MoCA was performed on all participants. The relationship between rs-fMRI information, neuropsychological status, and paraclinical data was analyzed., Results: The COVID-19 group got a lower mean MoCA score and showed a significant reduction in the functional connectivity of the IC14 (P<0.001) and IC38 (P<0.001) regions compared to the controls. The increase in functional connectivity was observed in the COVID-19 group compared to the controls at baseline in the default mode network (DMN) IC00 (P<0.001) and dorsal attention network (DAN) IC08 (P<0.001) regions. Furthermore, the alternation of functional connectivity in the mentioned ICs was significantly correlated with the mean MoCA scores and inflammatory parameters, i.e. erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)., Conclusion: Functional connectivity abnormalities in four brain neural circuits are associated with cognitive impairment and increased inflammatory markers in patients with COVID-19., Highlights: The patients with coronavirus-2019 (COVID-19) got a lower mean Montreal cognitive assessment (MoCA) score.The patients with COVID-19 showed significant reduction in the functional connectivity of the IC14 and IC38 regions.The patients with COVID-19 showed significant increase of functional connectivity in the default mode network (DMN) IC00 and dorsal attention network (DAN) IC08 regions.Alternation of functional connectivity was significantly correlated with the mean MoCA scores and ESR and CRP., Plain Language Summary: The researcher aimed at assessing cognitive impairments and investigating the whole-brain functional connectivity using resting state fMRI in patients with COVID-19 compared with healthy control group. The result showed That COVID-19 group got a lower mean cognitive score and showed a significant reduction in the functional connectivity of the IC14 and IC38 regions of brain compared with controls. Also, the increase of functional connectivity was observed in the COVID-19 group compared with controls at baseline in the default mode network (DMN) and dorsal attention network (DAN) regions of brain. Moreover, Functional connectivity abnormalities in four brain neural circuits associated with cognitive impairment and increased inflammatory markers in patients with COVID-19., Competing Interests: The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Background: Methamphetamine (MA), is a widely abused synthetic psychostimulant that leads to irreversible brain damage manifested as cognitive impairments in humans and animals. The novel object recognition (NOR) task is a commonly used behavioral assay for the investigation of non-spatial memory in rodents. This test is based on the natural tendency of rodents to spend more time exploring a novel object than a familiar one. NOR test has been used in many studies investigating cognitive deficits caused by MA in rodents. The objective of the present study was to review neurobiological mechanisms that might be responsible for MA-induced NOR alterations., Methods: A PubMed search showed 83 publications using novel object recognition and methamphetamine as keywords in the past 10 years., Findings: The present study revealed different MA regimens cause recognition memory impairment in rodents. In addition, it was found that the main neurobiological mechanism involved in MA-induced recognition deficits is the dysfunction of monoaminergic systems., Conclusion: NOR is a useful test to assess the cognitive functions following MA administration and evaluate the efficacy of new therapeutic agents in MA-addicted individuals., Competing Interests: Competing Interests The authors declare no competing interests., (© 2023 Kerman University of Medical Sciences.)

Introduction: It has long been known that Methamphetamine (MA), as a psychostimulant, leads to long-lasting cognitive deficits. Previous studies have shown that lithium, a mood stabilizer, could facilitate cognitive ability in most of brain diseases. In current study the effects of lithium on spatial memory, hippocampal apoptosis and brain edema in METH-exposed rats are investigated., Methods: The present study 32 Wistar rats were used to examine the effects of lithium on spatial memory by the Morris water maze, hippocampal apoptosis using the TUNEL assay, and brain edema following MA administrations., Results: The findings indicated that treatment with lithium significantly ameliorated spatial learning and memory impairment in MA-treated rats. In addition, the findings showed that treatment with lithium significantly reduced brain edema and apoptosis in the CA1 neurons in MA -exposed rats., Conclusion: The results show that treatment with lithium can partially ameliorate the MA-induced neurocognitive deficits in rats, which may be related to its protective effect in the hippocampus., Competing Interests: The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Thyroid hormones (THs) have an essential role in normal brain development and function. Methamphetamine (MA) is a widely abused psychostimulant that induces irreversible damages to neuronal cells. In the current study, we used rat primary hippocampal neurons (PHNs) to investigate the neuroprotective effect of THs against MA neurotoxicity. PHNs were prepared from 18-day rat embryos and cell viability was assessed using MTT assay, following treatment with various concentrations of MA, T3, T4 or tetrac, an integrin αvβ3 cell surface receptor antagonist. Our results showed that 7 mM MA induced an approximately 50 % reduction in the PHNs viability. Treatment with 800 nM T3 or 8 μM T4 protected PHNs against MA toxicity, an effect which was blocked in the presence of tetrac. These findings suggest that THs protect PHNs against MA-induced cell death by the activation of integrin αvβ3 cell surface receptors. So, targeting integrin αvβ3 receptors or using THs can be considered as promising therapeutic strategies to overcome MA neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The present study aimed to compare lapse and relapse-free survival between patients treated in Narcotics Anonymous (NA) groups and Methadone Maintenance Treatment (MMT) centers and to determine the relationship between social support scale and treatment outcome. Method: This study was a prospective, 12-month cohort study using the random sampling method to select 100 newcomer patients treated by the NA Association as well as 100 patients in MMT centers. The data were collected using a demographic questionnaire and Social Support Appraisals (SSA) scale at the onset of the study along with follow-up phone calls every other week. Results: All participants were male, aged between 18 and 65 with a mean (SD) age of 38.98 (± 10.85) years. Prevalence of relapse in 12 months was 60.5%. The lapses in the MMT group and relapses in the NA group were significantly higher (P < 0.001). The younger patients with lower levels of education are at greater risk of lapse/relapse. The mean score of SSA was significantly higher in the MMT group than the NA group in all subscales, including friends, family, and the others' support (P < 0.001). The mean scores of SSA subscales for the participants without relapse in the NA group was significantly higher in comparison to the MMT group. Conclusion: Detection of factors related to drug abuse relapse/lapse may help addiction therapists to identify drug abuse patients with lapse/relapse and to develop treatment and policy guidelines to prevent relapse in addiction recovery., (Copyright © 2022 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Methamphetamine (METH) may cause long‒lasting neurotoxic effects and cognitive impairment. On the other hand, the ovarian hormones estrogen and progesterone have neuroprotective effects. In the current study, we aimed to examine the effects of estrogen and progesterone on anxiety‒like behavior and neuronal damage in METH‒exposed ovariectomized (OVX) rats. Three weeks after ovariectomy, the animals received estrogen (1 mg/kg, i.p.), or progesterone (8 mg/kg, i.p.), or estrogen plus progesterone (with the same doses), or vehicle during 7 consecutive days (days 22-28). On day 28, OVX rats were exposed to a single‒day METH regimen (6 mg/kg, four s.c. Injections, with 2 h interval) 30 min after the hormone treatment. The next day (on day 29), the animals were assessed for anxiety‒related behaviors using the open field and elevated plus‒maze tasks. The animals were then sacrificed and brain water content, cell apoptosis and expression of IL-1β were evaluated. The findings showed that treatment with estrogen or progesterone alone in METH‒exposed rats significantly improved hyperthermia, anxiety‒like behavior, neuronal damage, and inflammation in the CA1 area. Also, treatment with estrogen plus progesterone improved hyperthermia and brain edema. Taken together, the findings suggest that treatment with ovarian hormones can partially prevent hyperthermia and anxiety‒related behaviors induced by METH in OVX rats, which could be accompanied by their neuroprotective effects in the hippocampus., (Copyright © 2021. Published by Elsevier B.V.)

Chronic use of methamphetamine (MA), a neurotoxic psychostimulant, leads to long-lasting cognitive dysfunctions in humans and animal models. Thyroid hormones (THs) have several physiological actions and are crucial for normal behavioral, intellectual and neurological development. Considering the importance of THs in the cognitive processes, the present study was designed to evaluate the therapeutic effects of THs on cognitive and neurological impairments induced by MA. Escalating doses of MA (1-10 mg/kg, IP) were injected twice daily for 10 consecutive days in rats and cognitive functions were evaluated using behavioral tests. The expression of factors involved in neurogenesis (NES and DCX), mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM), neuroinflammation (GFAP, Iba-1, and COX-2) as well as Reelin and NT-3 (synaptic plasticity and neurotrophic factor, respectively) was measured in the hippocampus of MA-treated animals. The effects of three different doses of T4 (20, 40 or 80 μg/kg; intraperitoneally) or T3 (20, 40 or 80 μg/rat; 2.5 μl/nostril; intranasal) treatment, once a day for one week after MA cessation, were assessed in MA-treated rats. After the last behavioral test, serum T4 and T3 levels were measured using radioimmunoassay. The results revealed that repeated escalating regimen of MA impaired cognitive functions concomitant with neurogenesis and synaptic plasticity impairments, mitochondrial dysfunction, and neuroinflammation. T4 or T3 treatment partially decreased the alterations induced by MA. These findings suggest that THs can be considered as potential candidates for the reduction of MA abuse related neurocognitive disturbances., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Neurocognitive impairment in response to methamphetamine (MA) has been proven in a variety of experimental and clinical studies. Elucidation of the underlying mechanisms of MA-induced cognitive deficits and finding preventive/therapeutic approaches need best-suited animal models. In modeling repeated MA exposure, while some believes that escalating doses simulate drug abuse conditions, others believe this regimen confers a preconditioning protection. The present study aimed to compare the effects of three different regimens of repeated MA administration on memory and cognitive function of adult rats. Rats in two different experimental groups were treated with escalating paradigms consisted of twice-daily i.p. injections; 1-4 mg/kg over 7 days or 1-10 mg/kg over 10 days. The third group received twice-daily doses of 15 mg/kg every other day over 14 days. Spatial working memory, novel object recognition task and anxiety-like behavior were measured sequentially in all MA-treated rats and vehicle-treated controls started from day 8 after last injection. All MA regimens decreased rates of spontaneous alternation in Y-maze and increased anxiety-like response. Short-term recognition memory was unchanged across all MA-treated animals, while long-term memory was impaired in the second and third MA regimen. Though MA deleterious effect especially in recognition memory is somehow dose dependent, preconditioning effect of increasing doses may be ruled out at least in the case of parameters measured here.

Long-term use of methamphetamine (MA) causes a broad range of cognitive deficits. Recently, it has been reported insulin signaling and mitochondrial biogenesis are involved in cognitive processes. This study aimed to examine whether MA induces cognitive deficits concomitant with insulin signaling impairment and mitochondrial dysfunctions and also intranasal (IN) insulin treatment can reverse cognitive deficits caused by MA. Rats were repeatedly treated with increasing doses of MA (1-10 mg/kg) twice a day for 10 days, and their cognitive functions were assessed using Y-maze, novel object recognition and passive avoidance tasks. The expression of components involved in insulin signaling (IR/IRS2/PI3K/Akt/GSK3β) and mitochondrial biogenesis (PGC-1α, NRF1, and TFAM) was measured in the hippocampus. Therapeutic effects of IN insulin delivery (0.5- IU/day, for 7 days after MA discontinuation) were also investigated in MA-treated animals. Our results showed that repeated MA exposure induced cognitive deficits, and led to insulin signaling impairment and mitochondrial dysfunction. Interestingly, IN insulin treatment reduced MA-induced cognitive impairments possibly through activating insulin signaling, particularly PI3K/Akt/GSK3β pathway, and mitochondrial biogenesis. Thus, insulin and insulin signaling pathway can be considered as useful targets for the treatment of abnormalities associated with MA abuse., (© 2017 Wiley Periodicals, Inc.)

Insulin, as a peptide hormone, has recently gained attention for its pro-cognitive, anti-inflammatory and neuroprotective effects in the central nervous system (CNS). Most studies have indicated anxiogenic and neuroinflammatory effects of methamphetamine (MA) and other psychostimulants, even after periods of abstinence. The present study aimed to examine whether intranasal (IN) insulin treatment with high CNS bioavailability and minimal systemic side effects, can reverse the anxiety-like behavior and neuroinflammation induced by repeated MA administration. In male wistar rats, escalating doses of MA (1-10mg/kg, i.p.) were administrated twice a day for 10 consecutive days. IN insulin treatment (0.5IU/day, for 7days after MA discontinuation) attenuated MA-induced anxiety-like behavior in the elevated plus maze task, and significantly decreased the levels of glial cell markers (GFAP and Iba1), pro-inflammatory cytokines (TNF-α and IL-6) as well as COX2 and NF-κB players of neuroinflammation, in the hippocampus of MA-treated animals. These findings introduce insulin as a potential therapeutic approach for the treatment of MA aversive symptoms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Several biological and medical benefits of Saffron, Crocus sativus (Iridaceae), have been demonstrated. However, mechanisms of actions for purified constituents are greatly unknown., Objective: To examine the effects of Safranal, a main constituent of Saffron stigma, on cell viability and cytokine profile of peripheral blood mononuclear cells (PBMC) were examined., Methods: Effects of Safranal at 0.1, 0.5 and 1 mM concentrations were evaluated on cell viability and production of interleukin 4 (IL-4), IL-10 and interferon-γ (IFN-γ) from non-stimulated and phytohemagglutinin (PHA) stimulated PBMCs, compared to 0.1 mM dexamethasone and saline., Results: In stimulated cells, different concentrations of Safranal caused significant decrease of lymphocytes viability (p<0.001 for all concentrations). All concentrations of Safranal inhibited IFN-γ and IL-10 secretion in stimulated cells (p<0.01). In addition, higher concentrations of Safranal significantly decreased cell viability of non-stimulated PBMCs (p<0.001). The effect of 1 mM Safranal on IL-4 secretion was less than dexamethasone (p<0.05). Safranal showed a stimulatory effect on IFN-γ secretion in non-stimulated cells. The IFN-γ/IL-4 ratio at the presence of two higher Safranal concentrations both in non-stimulated and stimulated cells were significantly higher than those of control and PHA stimulated groups, respectively (p<0.05)., Conclusion: The IFN-γ/IL-4 ratio increases in the presence of Safranal which indicates an effect on Th1/Th2 balance. Therefore, Safranal may have therapeutic effects in inflammatory diseases associated with Th1/Th2 imbalance.

The effects of macerated extracts of Crocus sativus (Family Iridaceae) (saffron) on cell viability and cytokine release of stimulated peripheral blood mononuclear cells by phytohemagglutinin (PHA) and nonstimulated cells were examined. The effects of three concentrations of macerated extract, dexamethasone, and saline on cell viability and production of cytokines, including interleukin (IL)-4, IL-10, and interferon-γ (IFN-γ) were evaluated. In cells stimulated with PHA, different concentrations of the extract significantly inhibited cell viability of lymphocytes (P<.001 for all concentrations). High concentrations of the extract (500 μg/mL) also inhibited secretion of IFN-γ in stimulated cells and IL-10 secretion in both stimulated and nonstimulated cells (P<.05 for all cases). The effects of high and low concentrations of the extract (500 and 50 μg/mL, respectively) on IL-4 secretion were lower than that of dexamethasone (P<.05 to P<.001). The extract showed a stimulatory effect on IFN-γ and IL-4 secretion in nonstimulated cells. The ratios of IFN-γ to IL-4 in the presence of all concentrations of saffron on stimulated cells were significantly higher than for the control group (P<.05 to P<.01). These results indicated that the extract of saffron leads to increased ratio of IFN-γ to IL-4.