Intranasal CEPO-FC prevents attention deficits in streptozotocin-induced rat model of Alzheimer's disease: Focus on synaptic plasticity-related factors.

Alzheimer's disease remains an issue of great controversy due to its pathology. It is characterized by cognitive impairments and neuropsychiatric symptoms. The FDA approved medications for this disease, can only mitigate the symptoms. One reason for the lack of effective medications is the inaccessibility of the brain which is encompassed by the blood-brain barrier, making intranasal (IN) route of administration potentially advantageous. Male Wistar rats underwent stereotaxic surgery to induce an Alzheimer's disease model via intracerebroventricular (ICV) streptozotocin injection, and Carbamylated Erythropoietin-Fc (CEPO-FC), a derivative of Erythropoietin without its harmful characteristics, was administered intranasally for ten consecutive days. Cognition performance for memory and attention was assessed using the Novel Object Recognition Test and the Object-Based Attention Test respectively. Depression like behavior was evaluated using the Forced Swim Test. Western blotting was done on the extracted hippocampus to quantify STIM proteins. Calbindin, PSD-95, Neuroplastin, Synaptophysin and GAP-43 genes were assessed by Realtime PCR. Behavioral tests demonstrated that IN CEPO-FC could halt cognition deficits and molecular investigations showed that, STIM proteins were decreased in Alzheimer's model, and increased after IN CEPO-FC treatment. Calbindin and PSD-95 were downregulated in our disease model and upregulated when treated with IN CEPO-FC. While Neuroplastin, and GAP-43 expressions remained unchanged. This study suggests that IN CEPO-FC in low doses could be promising for improving cognition and synaptic plasticity deficits in Alzheimer's disease and since IN route of administration is a convenient way, choosing IN CEPO-FC for clinical trial might worth consideration. See also the graphical abstract(Fig. 1).

Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease.

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.

Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Reduction of ovarian reserves and activation of necroptosis to in vivo air pollution exposures.

We investigated the association between air pollution and changes in ovarian follicles, anti-mullerian hormone (AMH) levels, the occurrence of necroptosis cell death by activation of receptor-interacting protein kinase 3 (RIPK3) and, the activation of mixed lineage kinase domain-like (MLKL) proteins. Forty-two female Wistar rats were divided into three groups of 14 each, which were exposed to real-ambient air, filtered air and purified air (control) in two periods of 3 and 5 months. The results showed that the number of ovarian follicles decreased in the group exposed to real-ambient air versus the control group (P < 0.0001). The trend of age-related AMH changes with respect to exposure to air pollutants was affected and its levels decreased after 3 months of exposure. The MLKL increased in the group exposed to the real-ambient air compared to the control group (P = 0.033). Apparently long-term exposure to air pollution can reduce ovarian reserves.

Neuroprotective Effects of Ferrostatin and Necrostatin Against Entorhinal Amyloidopathy-Induced Electrophysiological Alterations Mediated by voltage-gated Ca2+ Channels in the Dentate Gyrus Granular Cells.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the main form of dementia. Abnormal deposition of amyloid-beta (Aß) peptides in neurons and synapses cause neuronal loss and cognitive deficits. We have previously reported that ferroptosis and necroptosis were implicated in Aß25-35 neurotoxicity, and their specific inhibitors had attenuating effects on cognitive impairment induced by Aß25-35 neurotoxicity. Here, we aimed to examine the impact of ferroptosis and necroptosis inhibition following the Aß25-35 neurotoxicity on the neuronal excitability of dentate gyrus (DG) and the possible involvement of voltage-gated Ca2+ channels in their effects. After inducing Aß25-35 neurotoxicity, electrophysiological alterations in the intrinsic properties and excitability were recorded by the whole-cell patch-clamp under current-clamp condition. Voltage-clamp recordings were also performed to shed light on the involvement of calcium channel currents. Aß25-35 neurotoxicity induced a considerable reduction in input resistance (Rin), accompanied by a profoundly decreased excitability and a reduction in the amplitude of voltage-gated calcium channel currents in the DG granule cells. However, three days of administration of either ferrostatin-1 (Fer-1), a ferroptosis inhibitor, or Necrostatin-1 (Nec-1), a necroptosis inhibitor, in the entorhinal cortex could almost preserve the normal excitability and the Ca2+ currents. In conclusion, these findings suggest that ferroptosis and necroptosis involvement in EC amyloidopathy could be a potential candidate to prevent the suppressive effect of Aß on the Ca2+ channel current and neuronal function, which might take place in neurons during the development of AD.

Preparation and characterization of brain-targeted polymeric nanocarriers (Frankincense-PMBN-lactoferrin) and in-vivo evaluation on an Alzheimer's disease-like rat model induced by scopolamine.

Experiments have demonstrated that frankincense may offer protection against scopolamine-induced Alzheimer's disease by mitigating cholinergic dysfunction and inhibiting inflammatory mediators. Nevertheless, its instability and limited water solubility lead to diminished medicinal efficacy. In this study, we utilized PMBN (poly [MPC-co-(BMA)-co-(MEONP)]) as a nanocarrier for targeted brain drug delivery of frankincense, employing lactoferrin as a ligand for precise targeting. Characterization of nanoparticle properties was conducted through FTIR and FESEM analysis, and the in-vitro drug release percentage from the nanoparticles was quantified. To induce Alzheimer's-like dementia in rats, scopolamine was intraperitoneally administered at a dose of 1 mg/kg/day for 14 days. Subsequently, behavioral assessments (Y-maze, passive avoidance test, tail suspension test) were performed, followed by evaluations of acetylcholinesterase (AChE), reduced glutathione (GSH), catalase (CAT), and brain histopathology at the conclusion of the treatment period. The results revealed that the nanoparticles had a size of 106.6 nm and a zeta potential of -3.8 mV. The maximum release of frankincense in the PBS environment from PMBN nanoparticles was 18.2 %, in accordance with the Peppas model. Behavioral tests indicated that targeted drug nanoparticles (F-PMBN-Lf) exhibited the capability to alleviate stress and depression while enhancing short-term memory in scopolamine-induced animals. Additionally, F-PMBN-Lf counteracted the scopolamine-induced elevation of AChE activity and GSH levels. However, it resulted in decreased activity of the antioxidant enzyme CAT compared to the scopolamine group. Histological analysis of brain tissue suggested that F-PMBN-Lf exerted a notable neuroprotective effect, preserving neuronal cells in contrast to the scopolamine-induced group. It appears that the polymer nanoparticles containing this plant extract have introduced a novel neuroprotective approach for the treatment of Alzheimer's disease.

Paternal Aggression in Early-life Impairs the Spatial Memory and Passive Avoidance Learning in Adulthood of Male Rats: The Possible Role of DRD2.

Introduction: Negative early-life experiences (e.g. having an aggressive father) can leave long-lastingimpacts on the behavior. However, it is not clear if they influence learning and memory. Methods: In this study, we investigated the influences that the presence of an aggressive father had on the level of passive avoidance learning and spatial memory. We also studied the changes in the dopamine receptor D2 (DRD2) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) gene expression in the hippocampus. Then, we evaluated if a DRD2 antagonist (sulpiride, 0.125, 0.25, or 0.5 µg/rat) could modulate these changes. Results: We found that the subjects exposed to early-life stress made by aggressive fathers had impaired passive avoidance learning and spatial memory compared to subjects with normal fathers. Treatment with sulpiride improved passive avoidance learning and spatial memory in rats with aggressive fathers. The rats with aggressive fathers also had higher expression of the DRD2 gene in their hippocampus than those with normal fathers, while the PGC-1α gene expression was not different among groups. Treatment with sulpiride (0.125, 0.25, or 0.5 µg/rat) reduced the DRD2 gene expression in those with aggressive fathers to the normal level compared to those with normal fathers. Conclusion: These data suggest that having and living in a shared place with an aggressive father, even without any physical contact, can detrimentally affect passive avoidance learning and spatial memory which is accompanied by the increased expression of the DRD2 gene. Also, sulpiride as a dopaminergic antagonist could reverse this process. Highlights: Having and living with an aggressive father reduced learning and memory in offspring.Having and living with an aggressive father during early life increased DRD2 gene expression.Sulpiride improved learning and memory and also normalized DRD2 gene expression.A combination of genetic and environmental factors may modulate learning and memory. Plain Language Summary: In this study, we looked at how having an aggressive father, can affect behavior in the long term. We wanted to find out if this factor influences learning and memory. To do this, we investigated how the presence of an aggressive father affected passive avoidance learning and spatial memory in subjects. We also examined specific genes in the brain, called DRD2 and PGC-1α, which are known to be involved in learning and memory. Specifically, we wanted to see if the expression of these genes in the hippocampus (a region of the brain important for memory) was affected by having and presence of an aggressive father. To understand the role of the DRD2 gene further, we used a drug called sulpiride, which blocks the action of DRD2. We administered sulpiride to the subjects with aggressive fathers to see if it could reverse any negative effects on learning and memory. What we found was that subjects that had aggressive fathers had impaired passive avoidance learning and spatial memory compared to those with normal fathers. However, when we treated the subjects with sulpiride, their learning and memory improved. Additionally, we observed that rats with aggressive fathers had higher levels of the DRD2 gene in their hippocampus, while the PGC-1α gene expression was not different among the groups. The administration of sulpiride reduced the expression of the DRD2 gene in rats with aggressive fathers, bringing it back to normal levels similar to those with normal fathers. These findings suggest that having and living in the same environment as an aggressive father, even without direct physical contact, can negatively impact passive avoidance learning and spatial memory. This effect seems to be associated with increased expression of the DRD2 gene. However, using sulpiride as a dopaminergic antagonist can reverse this process and improve learning and memory in these subjects.

Does hazelnut consumption affect brain health and function against neurodegenerative diseases?

INTRODUCTION: A healthy daily diet and consuming certain nutrients, such as polyphenols, vitamins, and unsaturated fatty acids, may help neuronal health maintenance. Polyphenolic chemicals, which have antioxidant and anti-inflammatory properties, are involved in the neuroprotective pathway. Because of their nutritional value, nuts have been shown in recent research to be helpful in neuroprotection. OBJECTIVE: Hazelnut is often consumed worldwide in various items, including processed foods, particularly in bakery, chocolate, and confectionery products. This nut is an excellent source of vitamins, amino acids, tocopherols, phytosterols, polyphenols, minerals, and unsaturated fatty acids. Consuming hazelnut may attenuate the risk of neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease due to its anti-inflammatory and anti-oxidant qualities. RESULTS: Many documents introduce hazelnut as an excellent choice to provide neuroprotection against neurodegenerative disorders and there is some direct proof of its neuroprotective effects. DISCUSSION: So hazelnut consumption in daily diet may reduce neurodegenerative disease risk and be advantageous in reducing the imposed costs of dealing with neurodegenerative diseases.

Sirtuins and Metabolism Biomarkers in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: a Correlation Study with Clinical Outcomes and Cognitive Impairments.

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS. We measured sirtuin (SIRT) 1 and 3 levels, mitochondrial complex I, IV, aconitase, and α-ketoglutarate dehydrogenase (α-KGD) activity in the peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate, and cytochrome c (Cyt c) were determined in plasma. Finally, we performed postmortem tissue immunohistochemistry to assess the level of SIRT1 and SIRT3 in the brain lesions of patients with MS.Increased disability and cognitive impairment in patients were correlated. Plasma level of lactate showed a correlation with the disability in MS patients; moreover, a trend toward increased Cyt c plasma level was observed. Investigation of PBMCs exhibited decreased SIRT1 during the relapse phase along with a reduced complex IV activity in all MS subgroups. α-KGD activity was significantly increased in the RR-remission, and SIRT3 was elevated in RR-relapse group. This elevation correlated with disability and cognitive impairment. Finally, immunohistochemistry demonstrated increased levels of SIRT1 and 3 in the brain active lesion of patients with MS.Our data suggest that mitochondrial dysfunction and alteration in some epigenetics and metabolism modifying factors in the CNS and peripheral blood cells may contribute or correlate with MS progression.

Long-term exposure to air pollution and anti-mullerian hormone rate of decline: a population-based cohort study in Tehran, Iran.

Anti-mullerian hormone (AMH) concentration is a marker of ovarian reserve that decreases with age. However, a decrease in AMH may occur more rapidly under the influence of environmental factors. The present study investigated the association between long-term exposure to ambient air pollutants with serum concentrations of AMH and the AMH rate of decline. This study included 806 women with median age of 43 years (interquartile range: 38-48) participating in the Tehran Lipid and Glucose Study (TLGS) that were followed from 2005 to 2017. The AMH concentration and the demographic, anthropometric, and personal health parameters of the study participants were obtained from the TLGS cohort database. Air pollutant data were collected from the monitoring stations and the individual exposures were estimated by previously developed land use regression (LUR) models. Multiple linear regression analysis was used to estimate linear relationships between the air pollutant exposures and serum concentration of AMH and with the AMH declination rate. The results show no statistically significant associations between exposures to any of the air pollutants (including PM10, PM2.5, SO2, NO, NO2, NOX, and benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX) with serum concentration of AMH. Compared to the first tertile, no statistically significant associations were observed between the second or third tertiles of air pollutants, with the AMH rate of decline. In this study, we did not find significant association between air pollution and AMH in middle age women in Tehran, Iran. Future work may study such associations in younger women.

Effect of sex differences and time of oxytocin administration on treatment of rat model of autism spectrum disorder: Focused on necroptosis markers.

Autism is a neurodevelopmental disorder. A variety of molecular and cellular abnormalities leads to behavioral deficits in autism. Nevertheless, its etiology and treatment strategy are not completely understood. Oxytocin has recently shown improvements in social functioning. This study aimed to evaluate the necroptosis pathway for the neuroprotective effects of oxytocin in the valproic acid-induced autism spectrum disorder model. The autism spectrum disorder was induced by valproic acid on gestational day 12.5 (600 mg/kg, intraperitoneally). Offspring received intranasal oxytocin (1 µg/µL) on the 21st and 40th days after birth. The offspring behaviors were scrutinized by self-grooming, marble-burying, three-chamber, and Morris water maze tests. Western blot was performed on the hippocampus and amygdala tissues to investigate the expression of RIP3 and MLKL markers. The valproic acid group demonstrated more anxiety, repetitive behaviors, and expression of RIP3 and MLKL markers, and less social interaction and spatial memory compared with the control group. Oxytocin considerably improved social interactions, preference for social novelty, and memory. The elevated expression of RIP3 and MLKL markers in valproic acid-induced autistic rats were alleviated after treatment with oxytocin. We also highlighted the importance of age and gender in autism spectrum disorder interventions. Our findings suggested that oxytocin administration was as an effective treatment in two areas of repetitive/stereotyped behaviors, social interactions/cognitive function. Notably, early administration of oxytocin resulted in better therapeutic responses in autism-like behaviors. The molecular tests introduce oxytocin as a potential candidate for reducing the expression of necroptosis mediators in the brain. This reinforced our hypothesis that the necroptosis pathway takes part in autism spectrum disorder.

Endoplasmic reticulum stress inhibition ameliorated WFS1 expression alterations and reduced pancreatic islets' insulin secretion induced by high-fat diet in rats.

Endoplasmic reticulum (ER) stress is involved in the development of glucose homeostasis impairment. When ER stress occurs, the unfolded protein response (UPR) is activated to cope with it. One of the UPR components is WFS1 (Wolfram syndrome 1), which plays important roles in ER homeostasis and pancreatic islets glucose-stimulated insulin secretion (GSIS). Accordingly and considering that feeding high-fat food has a major contribution in metabolic disorders, this study aimed to investigate the possible involvement of pancreatic ER stress in glucose metabolism impairment induced by feeding high-fat diet (HFD) in male rats. After weaning, the rats were divided into six groups, and fed on normal diet and HFD for 20 weeks, then 4-phenyl butyric acid (4-PBA, an ER stress inhibitor) was administered. Subsequently, in all groups, after performing glucose tolerance test, the animals were dissected and their pancreases were removed to extract ER, islets isolation and assessment of GSIS. Moreover, the pancreatic ER stress [binding of immunoglobulin protein (BIP) and enhancer-binding protein homologous protein (CHOP)] and oxidative stress [malondialdehyde (MDA), glutathione (GSH) and catalase] biomarkers as well as WFS1 expression level were evaluated. HFD decreased pancreatic WFS1 protein and GSH levels, and enhanced pancreatic catalase activity, MDA content, BIP and CHOP protein and mRNA levels as well as Wfs1 mRNA amount. Accordingly, it increased BIP, CHOP and WFS1 protein levels in the extracted ER of pancreas. In addition, the HFD caused glucose intolerance, and decreased the islets' GSIS and insulin content. However, 4-PBA administration restored the alterations. It seems that, HFD consumption through inducing pancreatic ER stress, altered WFS1 expression levels, reduced the islets' GSIS and insulin content and finally impaired glucose homeostasis.

Cytotoxic effects of crystalline silica in form of micro and nanoparticles on the human lung cell line A549.

Airborne crystalline silica (SiO2) particles are one of the most common pollutants in stone industries. Limited studies have investigated the health effects of crystalline SiO2 nanoparticles. Hence, the objective of this study was to study the cytotoxicity of SiO2 in nano and micron sizes. A mineral quartz sample in the range of 0.2-0.8 mm sizes was purchased. These particles were ground at about 5 and 0.1 microns. Human cell line A549 was exposed to micro and nanometer particles at concentrations of 10, 50, 100, and 250 µg/ml for 24 and 72 h. Subsequently, the cytotoxicity of exposed cells was investigated by measuring cell survival, ROS generation, mitochondrial permeability, and intracellular glutathione content. The results showed that crystalline SiO2 nano and microparticles decreased cell survival, increased ROS generation, damaged the mitochondrial membrane, and lowered the antioxidant content of these cells in a concentration- and time-dependent manner. The toxicity of crystalline SiO2 microparticles at concentrations ≤50 µg/mL was greater than for nanoparticles, which was the opposite at concentrations ≥100 µg/mL. Exposure time and concentration were crucial factors for the cytotoxicity of exposed A549 cells to crystalline SiO2 particles, which can affect the severity of the effect of particle size. Due to the limitation of exposure concentration and test durations in this study, further studies on the parameters of nanoparticle toxicity and underlying mechanisms could advance our knowledge.

Role of amyloid beta (25-35) neurotoxicity in the ferroptosis and necroptosis as modalities of regulated cell death in Alzheimer's disease.

Neuronal cell death as a prominent pathological feature contributes to cognitive decline and memory loss in Alzheimer's disease. We investigated the role of two forms of cell death pathways, ferroptosis and necroptosis, and their interactions following entorhinal cortex (EC) amyloidopathy. The Aß25-35 was bilaterally injected into the rat's EC, and Morris Water Maze was applied to determine spatial performance one week after Aß injection. For evaluation of ferroptosis and necroptosis involvement in Aß induced pathology, ferroptosis inhibitor, Ferrostatin (Fer-1), and necroptosis inhibitor, Necrostatin (Nec-1), were injected into the EC during training days of behavioral test. Our behavioral and histological assessment showed spatial learning and memory impairment, along with neuropathology changes such as cell survival and intracellular Aß deposits in response to EC amyloidopathy, which were ameliorated by treatment with Fer-1 or Nec-1. The expression of ferroptosis key factors GPX4 and SLC7A11 were decreased and the level of TfR was increased following Aß toxicity. Also, Necroptosis pathway related factors RIP1, RIP3, and MLKL were modulated by Aß neurotoxicity. However, application of Fer-1 or Nec-1 could inhibit the hippocampal ferroptosis and necroptosis pathways due to EC amyloidopathy. Our data also demonstrated that Aß-induced necroptosis suppressed by Fer-1, although Nec-1 had no effect on ferroptosis, indicating that ferroptosis pathway is upstream of necroptosis process in the Aß neurotoxicity. Moreover, Aß induced hippocampal mGLUR5 overexpression and reduced level of STIM1/2 recovered by Fer-1 or Nec-1. According to our findings ferroptosis and necroptosis pathways are involved in Aß neurotoxicity through modulation of mGLUR5 and STIM1/2 signaling.

Adverse effects of polystyrene nanoplastic and its binary mixtures with nonylphenol on zebrafish nervous system: From oxidative stress to impaired neurotransmitter system.

Micro(nano)plastics generally co-exist with other chemicals in the environment, resulting in inevitable interaction and combined toxic effects on biota. Nevertheless, little is known regarding the interaction of nanoplastics (NPs) with other co-occurring insults. Hereby, we investigated single and combined effects of chronic exposure (45 days) to polystyrene nanoplastic particulates (PS-NPs) and nonylphenol (4-NP) on zebrafish nervous system. Multiple biomarkers concerning with oxidative-stress [catalase (CAT) activity and reduced glutathione (GSH) level], cholinergic system [Acetylcholinesterase (AchE) activity], glutamatergic system [glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities], energy metabolism [a-ketoglutarate dehydrogenase (a-KGDH) activity], and histological alterations were assessed. Both single and binary exposure to PS-NPs and 4-NP induced oxidative stress through reducing CAT activity and GSH level, in which a more sever effect was noticed in combined exposure. The AchE activity was significantly inhibited only in single treatment groups demonstrating antagonistic interaction between PS-NPs and 4-NP. Effects on GS activity was also alleviated in binary exposure as compared with single exposure to each contaminant. In addition, an increase in GDH activity was noticed in PS-NPs at 10 and 100 µg/L, and simultaneous presence of PS-NPs and 4-NP with a greater response were observed in combined treatments. PS-NPs and 4-NP either in separate or binary mixtures disrupted energy metabolism by deficiency of α-KGDH activity; however, co-exposure to PS-NPs and 4-NP induced more intense adverse impacts on this parameter. Furthermore, histological analysis revealed that 4-NP and PS-NPs, alone or in combination, reduced neural cells. These findings provide new insight into the neurotoxic effects of binary exposure to PS-NPs and 4-NP at environmentally relevant concentrations. Overall, our findings raise concerns about the presence and toxicity of nano-scale plastic particulates and highlight the importance of investigating the interaction of Micro(nano)plastics with other environmental irritants.

Long-term high-fat diet disrupts lipid metabolism and causes inflammation in adult male rats: possible intervention of endoplasmic reticulum stress.

This study investigated the effect of long-term high-fat diet (HFD) on plasma lipid profile and probability of inflammation in adult rats. After weaning, male offspring were divided into six groups based on diet type and medication. After 20 weeks of dietary intake, 4-PBA (endoplasmic reticulum (ER) stress inhibitor) was injected for three days. Then, blood samples were taken to measure plasma concentrations of low-density lipoprotein (LDL), triglyceride (TG), high-density lipoprotein (HDL), cholesterol, leptin and interleukin 1-ß (IL 1-ß). The HFD increased body weight and food intake and intra-abdominal fat and thymus weights, which were associated with elevated plasma leptin level. Moreover, HFD increased plasma concentrations of TG, LDL, cholesterol and IL 1-ß and decreased HDL level. Injection of 4-PBA reversed the plasma parameters changes caused by HFD. It seems that long-term HFD feeding through inducing the ER stress, disrupted the lipid metabolism and resulted in inflammation.

A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies.

OBJECTIVE: Natural food substances, due to high rates of antioxidants, antiviral and anti-inflammatory properties, have been proposed to have the potential for the prevention or treatment of cognitive deficits, learning and memory deficits and neuro inflammation. In particular, medicinal plants with rich amounts of beneficial components such as flavonoids are one of the most promising therapeutic candidates for the cognitive deficit and memory loss. Herein, we aimed to review the impact of medicinal plants with focus on flavonoids on cognitive dysfunction, learning and memory loss by considering their signaling pathways. METHODS: We extracted 93 preclinical and clinical studies related to the effects of flavonoids on learning and memory and cognition from published papers between 2000 and 2021 in the MEDLINE/PubMed, Cochrane Library, SCOPUS, and Airiti Library databases. RESULTS: In the preclinical studies, at least there seem to be two main neurological and biological processes in which flavonoids contribute to the improvement and/or prevention of learning, memory deficit and cognitive dysfunction: (1) Regulation of neurotransmission system and (2) Enhancement of neurogenesis, synaptic plasticity and neuronal survival. CONCLUSION: Although useful effects of flavonoids on learning and memory in preclinical investigations have been approved, more clinical trials are required to find out whether flavonoids and/or other ingredients of plants have the potent to prevent or treat neurodegenerative disorders.

Almond intake during pregnancy in rats improved the cognitive performance of adult male offspring.

Background: Based on evidence there are accepted links among early nutrition, epigenetic processes, and cognitive performance. Almond as a nutritious food could exert neuroprotective effects and improve anxiety, learning, and memory.Methods: In the current study, female rats were fed with a diet containing 5% (w/w) almonds during the mating period (two days) and gestation period (21 consecutive days). Then, the effect of the almond diet on short-term memory (Y maze), anxiety (elevated plus maze), and stress adaptation (forced swimming test) were investigated in the adult male offspring. The hippocampus (HIP), prefrontal cortex (PFC), and amygdala (AMY) of offspring were collected, and the level of cyclic AMP response element-binding proteins (CREB), brain-derived neurotrophic factor (BDNF) was assessed by western blotting. Also, Monoamine oxidases (MAO)-A and B activity were evaluated via enzymatic assays.Results: Our results indicated that prenatal almond consumption improved memory, made a modest reduction in anxiety-like behavior, and increased stress adaptation in adult male offspring. Also, molecular assessments showed an increased level of CREB phosphorylation and BDNF in the HIP and PFC of the almond group, while the activity of MAO-A and MAO-B was inhibited by almond consumption in mentioned areas.Discussion: These findings introduce almonds as a beneficial diet during pregnancy, for improving short-term memory, stress adaptation, and cognitive performance in adult offspring.