The association of ultra-processed food intake with neurodegenerative disorders: a systematic review and dose-response meta-analysis of large-scale cohorts.

OBJECTIVES: Our systematic review and meta-analysis aimed to uncover the relationship between UPFs intake and neurodegenerative disorders, including multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), cognitive impairment, and dementia. SETTING: A systematic search was conducted using the Scopus, PubMed/MEDLINE, and ISI Web of Science databases without any limitation until June 24, 2023. Relative risk (RR) and 95% confidence interval (CI) were pooled by using a random-effects model, while validated methods examined quality and publication bias via Newcastle-Ottawa Scale, Egger's regression asymmetry, and Begg's rank correlation tests, respectively. RESULTS: Analysis from 28 studies indicated that a higher UPFs intake was significantly related to an enhanced risk of MS (RR = 1.15; 95% CI: 1.00, 1.33; I2 = 37.5%; p = 0.050; n = 14), PD (RR = 1.56; 95% CI: 1.21, 2.02; I2 = 64.1%; p = 0.001; n = 15), and cognitive impairment (RR = 1.17; 95% CI: 1.06, 1.30; I2 = 74.1%; p = 0.003; n = 17), although not AD or dementia. We observed that a 25 g increment in UPFs intake was related to a 4% higher risk of MS (RR = 1.04; 95% CI: 1.01, 1.06; I2 = 0.0%; p = 0.013; n = 7), but not PD. The non-linear dose-response relationship indicated a positive non-linear association between UPF intake and the risk of MS (Pnonlinearity = 0.031, Pdose-response = 0.002). This association was not observed for the risk of PD (Pnonlinearity = 0.431, Pdose-response = 0.231). CONCLUSION: These findings indicate that persistent overconsumption of UPFs may have an adverse impact on neurodegenerative conditions, potentially leading to a decline in quality of life and reduced independence as individuals age.

The role of glutamate NMDA receptors of the mediodorsal thalamus in scopolamine-induced amnesia in rats.

The current study was designed to examine the role of glutamate NMDA receptors of the mediodorsal thalamus (MD) in scopolamine-induced memory impairment. Adult male rats were bilaterally cannulated into the MD. According to the results, intraperitoneal (i.p.) administration of scopolamine (1.5 mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the glutamate NMDA receptors agonist, N-Methyl-D-aspartic acid (NMDA; 0.05 µg/rat), into the MD significantly improved scopolamine-induced memory consolidation impairment. Co-administration of D-AP5, a glutamate NMDA receptor antagonist (0.001-0.005 µg/rat, intra-MD) potentiated the response of an ineffective dose of scopolamine (0.5 mg/kg, i.p.) to impair memory consolidation, mimicking the response of a higher dose of scopolamine. Noteworthy, post-training intra-MD microinjections of the same doses of NMDA or D-AP5 alone had no effect on memory consolidation. Moreover, the blockade of the glutamate NMDA receptors by 0.003 ng/rat of D-AP5 prevented the improving effect of NMDA on scopolamine-induced amnesia. Thus, it can be concluded that the MD glutamatergic system may be involved in scopolamine-induced memory impairment via the NMDA receptor signaling pathway.

The effects of kindling during pregnancy on long-term potentiation (LTP) induction and M1 muscarinic acetylcholine receptors in male rat offspring.

Background and purpose: Neonates of pregnant women with epilepsy may compromise normal neurodevelopment and hippocampal morphology. Memory and learning disorders and a decrease in verbal IQ scores are seen in these children later in life. In the previous study, we suggested that the central muscarinic cholinergic receptors had an important role in learning and memory deficits induced by prenatal pentylenetetrazol-kindling in pups born to kindled mothers. This study aimed to investigate the effects of kindling during pregnancy on long-term potentiation (LTP) induction and the role of M1 muscarinic acetylcholine receptors in the hippocampus of male offspring. Experimental approach: Twenty female Wistar rats were divided into two groups on the 13th day of their gestation (kindled and control; n = 10). Animals in the first group were kindled by i.p. injections of 25 mg/kg body weight pentylenetetrazol every 15 min until seizures occurred and the control group received normal saline. The effect of maternal seizures and perfusion of specific M1 muscarinic receptors antagonist (telenzepine at doses of 0.01, 0.1, and 1 nmol) on the LTP induction of 80 pups were tested at 12 weeks of age by field potential recordings. Findings/Results: The results of the electrophysiological study revealed that recurrent seizures during pregnancy impaired field excitatory postsynaptic potentials (fEPSP)-LTP induction and normal development of M1 muscarinic receptors in the hippocampus of male offspring. Also, the results demonstrated that maternal seizure did not significantly affect the paired-pulse indexes and population spike-LTP in the hippocampus of male offspring. Conclusion and implications: Our study showed that recurrent seizures during pregnancy cause impaired fEPSP-LTP induction and abnormal development of the M1 muscarinic receptor in the hippocampus.

The association of ultra-processed food consumption with adult inflammatory bowel disease risk: a systematic review and dose-response meta-analysis of 4 035 694 participants.

CONTEXT: There is an inconsistency between the results obtained from observational studies regarding intake of ultra-processed foods (UPFs) and the risk of inflammatory bowel disease (IBD). OBJECTIVES: A dose-response meta-analysis was performed to evaluate the relationship between UPF intake and the risk of IBD. DATA SOURCES: Searches were performed in the PubMed, ISI Web of Science, and Scopus databases up to November 2, 2022. DATA EXTRACTION: Data were available from 24 studies including a total of 4 035 694 participants from 20 countries. DATA ANALYSIS: Risk ratios for IBD were analyzed by a random-effects model. Outcomes indicated that UPF intake was linked to an increased risk of IBD (relative risk [RR], 1.13; 95%CI, 1.06-1.21; P = 0.001; I2 = 73.2%; n = 59; N = 4 035 694). This association was significant, especially for the risk of Crohn's disease (CD) (RR, 1.19; 95%CI, 1.00-1.41; I2 = 78.2%; P = 0.046; n = 23; N = 2 167 160), unlike the risk of ulcerative colitis (UC) (RR = 1.11; 95%CI, 0.99-1.26; P = 0.085; I2 = 60.3%; n = 27; N = 2 167 918). Also, results revealed that each 10% enhancement in daily UPF intake was not related to the risk of IBD (RR, 1.05; 95%CI, 0.98-1.14; P = 0.168; I2 = 31.9%; n = 4) or the risk of UC (RR, 1.01; 95%CI, 0.92-1.11; P = 0.876; I2 = 34.7%; n = 2) in adults. However, results suggested that for every 10% increase in daily UPF intake, there was a 19% increase in the risk of CD (RR, 1.19; 95%CI, 1.01-1.32; P = 0.021; I2 = 0.0%; n = 2) among adults. In addition, the results showed a positive linear relation between UPF intake with CD risk (Pnonlinearity = 0.431; Pdose response = 0.049) but not risk of IBD or UC. CONCLUSION: High intake of UPFs was linked with an enhanced IBD risk, a specific risk of CD. However, conducting more observational studies among several ethnicities and using specific tools that accurately assess the amount of UPF consumption, components of UPFs, and food additives may be necessary. Systematic Review Registration: PROSPERO registration no. CRD42023390258.

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.

Synthesis, characterization and hypolipidemic effects of urazine derivatives on rat: Study of molecular modeling and enzyme inhibition.

The prevalence of hyperlipidemia has increased dramatically worldwide. It is a major public health threat, characterized by the presence of an abnormal lipid profile, primarily with elevated serum total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) levels, and reduced high-density lipoprotein (HDL) level. Genetic factors, dietary and lifestyle habits play important roles in hyperlipidemia. It can increase the risk of chronic metabolic disorders, such as obesity, cardiovascular disease, and type II diabetes. The main objective of the present study was to evaluate the effect of urazine derivatives on serum triglyceride, cholesterol, LDL, HDL, and nitric oxide (NO) levels in high-fat diet (HFD)-induced hyperlipidemic rats. Synthetic compounds were prepared and confirmed by spectroscopic methods. Then, 88 male Sprague-Dawley rats were divided into 11 groups: control, HFD-treated group, HFD plus atorvastatin-treated group, and HFD plus 8 synthetic compounds-treated groups. The body weight, triglyceride, cholesterol, LDL, HDL, and NO levels were measured. The data with p < 0.05 were considered significant. The results indicated that HFD significantly increased cholesterol, triglyceride, and LDL levels and decreased NO concentration and HDL level compared to the control group (p < 0.05). However, HFD plus urazine derivatives significantly decreased NO, cholesterol, and triglyceride levels and increased HDL levels compared to the HFD-treated group (p < 0.05). Urazine derivatives may improve liver dysfunction in HFD-induced hyperlipidemic rats by modulation of detoxification enzymes and their anti-oxidant effects and also blood lipid profile.

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.

Activation of androgen receptors alters hippocampal synaptic plasticity and memory retention through modulation of L-type calcium channels.

AIMS: It has been revealed that membrane androgen receptor activation modulates avoidance memory and synaptic plasticity. In a previous study, we showed that Calcineurin, a calcium dependent phosphatase, could be a potential mediator of these AR effects. Also, it is reported that AR activation leads to L-type calcium channel activation. The aim of the current study is to test whether L-type calcium channels are downstream of AR and whether this signal pathway mediates the impairment effect of androgenic steroids on passive avoidance memory and synaptic plasticity. MATERIALS AND METHODS: We measured the effect of Nandrolone Decanoate (AR agonist), AR antagonist (Nilutamide) plus ND or L-type calcium channel inhibitor (Nifedipine) plus ND on passive avoidance performance of adolescent male rats. For extracellular field potential recordings hippocampal slices were perfused with ND, Nilutamide-ND or Nifedipine-ND. KEY FINDINGS: Our results clarified that AR activation by ND could impair avoidance behavior as step through latency decreased in ND-treated group while application of both Nilutamide and Nifedipine reestablished normal avoidance behavior. Also, LTP induction in the CA1 area of hippocampus was diminished by ND perfusion and both AR antagonist and L-type calcium channel inhibitor application lead to normal LTP. These findings support our hypothesis that activation of L-type calcium channels are involved in ARs mechanism effects on both avoidance behavior and hippocampal synaptic plasticity. SIGNIFICANCE: Understanding the biological effects of AR agonists on cognitive processes and its cellular mechanism may be a new/supplementary way to treating fear-related disorders.

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.

The Relationship between Food Insecurity and Risk of Overweight or Obesity in under 18 Years Individuals: A Systematic Review and Meta-Analysis.

OBJECTIVE: Food insecurit (FI) has been considered as reason for childhood and adolescent overweight/obesity (OW/OB). Hence, this study was undertaken to assess these relationships. DESIGN: Related articles were found by searching the Web of Science, Scopus, PubMed and Embase databases until October 2019. Odds ratio (OR) was analized by a random-effects model. Standard methods were used for assessment of heterogeneity and publication bias. Data were available from 32 studies. The risk ratios of 139,762 participants were pooled from these articles for the meta-analysis. RESULTS: This study domenstrated that children and adolescents in food-insecure condition are not at risk of OW/OB (OR = 1.02 95% CI: 0.99, 1.05). However, subgroup analysis indicated that FI related with inhanced risk of OW/OB in adolescents living in developed countries (OR = 1.14; 95% CI: 1.02, 1.27). Other subgroup analysis indicated that severe FI increased the risk of OW/OB among adolescents (OR = 1.24 95% CI: 1.03-1.49). In addition, we found that lower economic development significantly decreased risk of OW/OB among under 6 year children (OR = 0.88; 95% CI: 0.84, 0.93). CONCLUSIONS: Our results showed that higher FI degrees were related with more risks of OW/OB among adolescents (12-18 years). Moreover, the country economic levels had effect on the association between FI and risk of OW/OB.

Effects of HDAC inhibitors on spatial memory and memory extinction in SPS-induced PTSD rats.

BACKGROUND AND PURPOSE: Neurobiological changes in memory processes seem to play a role in the pathophysiology of post-traumatic stress disorder (PTSD). Memory itself is influenced by PTSD, too. Histone deacetylase inhibitors (HDAIs) have shown promising results in the extinction of fear-related memories in animals and hence they seem to be important for the treatment of PTSD. Data are scarce about the effect of HDAIs in spatial memory formation/extinction in PTSD models. The main goal of the present work is to find the effect of sodium butyrate (NaBu), as an HDAI, on spatial memory and spatial memory extinction in rats exposed to single prolonged stress procedure (SPS). EXPERIMENTAL APPROACH: Different doses of NaBu were administered subcutaneously for 7 days in different groups of rats after SPS procedure. Learning, memory, and extinction of memory were evaluated in the Morris water maze test of spatial memory in 6 consecutive days. FINDINGS / RESULTS: The results show that NaBu (0.5 mg/kg) alleviates impaired learning and memory in SPS rats. It also facilitates the extinction of newly formed memory in the animals. CONCLUSION AND IMPLICATIONS: Our data suggest that the administration of HDAIs after a traumatic experience can prevent the aversive effects of SPS on spatial memory. It also reinforces the notion that extinction of spatial memory involves the same or similar brain circuitry that is involved in the extinction of fear memories in PTSD patients.

Sleep and frailty risk: a systematic review and meta-analysis.

PURPOSE: Studies on the association between sleep and frailty risk have yielded contradictory outcomes. Therefore, a systematic review and meta-analysis were designed to examine the relationship between sleep and frailty risk. METHODS: Relevant studies were identified by searching PubMed, Embase, and Scopus databases until 30 November 2019. Data were available from ten studies. Selected articles were published between 2009 and 2019. The odds ratios of 41,233 individuals were used for the meta-analysis. RESULTS: Pooled analysis demonstrated that when compared to the reference category of 6 to 8 hours nightly sleep duration, both the highest category (more than 8 hours, OR 1.21; 95% CI 1.10-1.32) and lowest category of sleep (under 6 hours, OR 1.13; 95% CI 1.08-1.18), were significantly correlated with increased risk of frailty. Furthermore, daytime drowsiness (OR 1.25; 95% CI 1.02-1.52), sleep disordered breathing (OR 1.28; 95% CI 1.03-1.58), and prolonged sleep latency (OR 1.18; 95% CI 1.06-1.31) enhanced the risk of frailty. Subgroup analyses by frailty status suggest that a shorter sleep duration was associated with risk of frailty but not pre-frailty. However, prolonged sleep time was significantly related with enhanced risk of pre-frailty and frailty. In addition, subgroup analyses via sex revealed that longer and shorter sleep durations increased risk of frailty in both men and women. CONCLUSION: The present study revealed that longer and shorter sleep durations are associated with increased risk of frailty.

Food insecurity and mental health: a systematic review and meta-analysis.

OBJECTIVE: Food security has been suggested to be a risk factor for depression, stress and anxiety. We therefore undertook a systematic review and meta-analysis of available publications to examine these associations further. DESIGN: Relevant studies were identified by searching Web of Science, Embase, Scopus and PubMed databases up to January 2019. SETTING: OR was pooled using a random-effects model. Standard methods were used for assessment of heterogeneity and publication bias. PARTICIPANTS: Data were available from nineteen studies with 372 143 individual participants from ten different countries that were pooled for the meta-analysis. RESULTS: The results showed there was a positive relationship between food insecurity (FI) and risk of depression (OR = 1·40; 95 % CI: 1·30, 1·58) and stress (OR = 1·34; 95 % CI: 1·24, 1·44) but not anxiety. Subgroup analysis by age showed that subjects older than ≥65 years exhibited a higher risk of depression (OR = 1·75; 95 % CI: 1·20, 2·56) than younger participants (OR = 1·34; 95 % CI: 1·20, 1·50), as well as a greater risk of depression in men (OR = 1·42; 95 % CI: 1·17, 1·72) than women (OR = 1·30; 95 % CI: 1·16, 1·46). Finally, subgroup analysis according to geographical location illustrated that food insecure households living in North America had the highest risk of stress and anxiety. CONCLUSIONS: The evidence from this meta-analysis suggests that FI has a significant effect on the likelihood of being stressed or depressed. This indicates that health care services, which alleviate FI, would also promote holistic well-being in adults.

Sleep duration and sarcopenia risk: a systematic review and dose-response meta-analysis.

PURPOSE: Present systematic literature review and dose-response meta-analysis were carried out to evaluate the association between sleep duration and sarcopenia risk. METHODS: Related studies were found by searching ISI Web of science databases, Scopus, and PubMed, up to May, 2019. Data were available from four studies. A total odds ratio of 17551 participants in these studies was pooled for the current study. RESULTS: Pooled outcomes from random effects model demonstrated that lowest category of sleep duration (under 6 h) versus reference category (6-8 h) was significantly related with increased risk of sarcopenia (OR: 1.71 95% CI, 1.11, 2.64). Pooled OR also indicated that highest category (more than 8 h) of sleep duration versus reference category (6-8 h) was significantly associated with increased risk of sarcopenia (OR: 1.52 95% CI, 1.23, 1.88). Moreover, subgroup analysis by sex showed that women were affected by both short and long sleep while men were only affected by long sleep duration. The nonlinear dose-response meta-analysis revealed a U-shaped association between sleep duration and the risk of sarcopenia, with a nadir at 8 h per day. The linear dose-response meta-analysis illustrated that the risk of sarcopenia did not change significantly nor for a 0.5-h increment neither for 1-h increment in sleep duration per day. CONCLUSION: The outcomes from this meta-analysis indicate that the public should be made aware of the negative consequences of long and short sleep for sarcopenia especially among women. Further studies should now be undertaken to establish possible links between risk of sarcopenia and sleep duration.

Nandrolone improve synaptic plasticity at the hippocampus CA1 area and spatial localization in the Morris water maze of male adolescent rats.

Nandrolone is the most popular compound that are mainly abused. Experimental studies have reported that administration of nandrolone affects cognitive performance. So, the aim of this study is to evaluate the effect of nandrolone on spatial localization and synaptic plasticity of male adolescent rats. Experimantal groups received DMSO and nandrolone (10, 30 and 60 µg, i.c.v.). Another aim is to evaluate the role of castration on spatial learning and memory changes induced by nandrolone. Therefore, the rats of fifth and sixth groups were castrated and received DMSO or nandrolone. Analysis showed that escape latency and traveled distance in the group which received nandrolone (60 µg) were significantly lower than control group. Also, the escape latency and traveled distance in the group of castration which received nandrolone was significantly higher than nandrolone treated group. The results of field potential recording showed that fEPSP-LTP in nandrolone-treated group was higher than DMSO-treated group. The magnitude of fEPSP-LTP in the group of castration which received nandrolone was significantly lower than nandrolone-treated group. The results demonstrated that nandrolone improved spatial learning, but castration could abolished nandrolone-induced spatial learning improvement. These results indicating that at least some effect of nandrolone on learning induced through changes in gonadal function.

Calcineurin is involved in retrieval of passive avoidance memory and synaptic plasticity impairment induced by Nandrolone administration in adolescent male rats.

In spite of evidence about negative effects of Nandrolone Decanoate (ND) on cognitive and memory performance, the underlying mechanisms are complex and have remained unclear. This research examines the role of Calcineurin in synaptic plasticity and memory storage impairment in ND administrated adolescent male rats. For behavioral study by passive avoidance learning and memory (PAL), adolescent male rats were treated with ND or ND plus selective Calcineurin antagonist (Tacrolimus), before retention test. ND significantly decreased the retrieval of PAL, whereas Tacrolimus plus ND had no significant effect on PAL. For electrophysiological study hippocampal slices were perfused by ND or ND plus Tacrolimus. The magnitude of fEPSP-LTP of ND perfused slices was less than the control and a reduction of fEPSP-PS (E-S) coupling was observed, while pre-administration of Tacrolimus abolished the ND impairment effect on fEPSP-LTP and E-S coupling. This study showed that ND may induce impairing effects on hippocampal area CA1 activity and plasticity and PAL memory storage through changes in the function of the Calcineurin.

Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats.

Despite the chronic effects of nandrolone decanoate (ND), the acute effects of ND on passive avoidance learning (PAL) and memory and its mechanism have not been investigated. This research examines the acute effect of ND on PAL, CA1 synaptic plasticity, testosterone and corticosterone serum levels, and the role of androgenic receptors (ARs). Adolescent male rats were treated with ND, 30 min before training and retention and after training test. AR antagonist was applied 15 min before ND. Hippocampal slices were perfused by ND. ND administration had an inverted U-shape effect on acquisition of PAL and on testosterone and corticosterone serum levels. The consolidation was only affected by high dose of ND. ND significantly decreased the retention of PAL across all doses. The magnitude of field excitatory postsynaptic potential long term potentiation was lower than that of control slices. In addition, an attenuation of field excitatory postsynaptic potential population spike coupling was also observed. Nilutamide could nullify the ND impairment effect. We concluded although a single dose of ND could affect all stages of PAL, its effects were more potent on retrieval, possibly arising from the acute effect of ND on the alterations of CA1 synaptic plasticity. In addition, ND may induce its effects directly through ARs and indirectly through plasma testosterone and corticosterone.