Locomotor Activity Test Research Articles

Chitosan-modified polymeric nanoparticles for the nose-to-brain drug delivery of paroxetine: an in vitro and in vivo evaluation.

This work focuses on the development of PLGA nanoparticles and their surface modification by chitosan to enhance the mucoadhesive properties and colloidal stability for intranasal delivery. Chitosan-coated paroxetine-loaded PLGA nanoparticles (PAR-CS-PLGA-NPs) were developed and characterized along with in vitro and in vivo evaluation. Particle size of 181.8 nm with a zeta potential of 36.3 mV was obtained. Entrapment efficiency % and drug loading % were 87.5% and 13.4%, respectively. TEM, FTIR, and DSC were also performed. In vitro drug release studies were conducted in phosphate buffered saline (pH 7.4) and simulated nasal fluid (pH 5.5), and sustained release was found until 72 h. Cellular assays on mammalian cells depicted the cell viability to be >60% even at the maximum concentration of PAR-CS-PLGA-NPs and showed significantly higher uptake than PLGA-NPs. Histopathological studies on the nasal epithelium showed no damage or inflammation when treated with PAR-CS-PLGA-NPs. In vivo studies were performed using Swiss albino mice to estimate the drug biodistribution after intranasal delivery of PAR-CS-PLGA-NPs. A significantly increased drug concentration was observed in the mouse brains (p < 0.05). Pharmacodynamics studies of the PAR-CS-PLGA-NPs were carried out by forced swimming test and locomotor activity test, demonstrating improved behavioral analysis parameters (p < 0.05). Thus, intranasal delivery of paroxetine-loaded mucoadhesive chitosan-coated PLGA nanoparticles could be potentially used for the treatment of depression.

Silymarin nanoparticles counteract cognitive impairment induced by doxorubicin and cyclophosphamide in rats; Insights into mitochondrial dysfunction and Nrf-2/HO-1 axis.

Most cancer patients suffer cognitive impairment following chemotherapy, recognized as "chemobrain". Principally, doxorubicin and cyclophosphamide are frequently utilized conjointly for the treatment of several kinds of tumors. Silymarin was reported to possess anti-inflammatory, antioxidant, and neuroprotective impacts. The recent study shed light on the neuroprotective attributes of silymarin against cognitive dysfunction instigated in rats with doxorubicin/cyclophosphamide combination. Unfortunately, silymarin suffers reduced absorption following oral administration. Silymarin was formulated as a nanoemulsion to be administered intranasally. Male rats were allocated into six groups: control, doxorubicin (2mg/kg, ip) and cyclophosphamide (50mg/kg, ip), doxorubicin and cyclophosphamide+silymarin (200mg/kg, oral), doxorubicin and cyclophosphamide+silymarin nanoemulsion (1mg/kg, intranasal), silymarin (200mg/kg, oral), and silymarin nanoemulsion (1mg/kg, intranasal) groups, and treated for 21 days. The amount of silymarin reaching the brain was found to be enhanced following formulated nanoemulsion administration. Doxorubicin and cyclophosphamide caused behavioral, as well as memory deficits indicated by locomotor activity, y maze, and passive avoidance tests. Also, they induced histological alteration in hippocampi and the prefrontal cortices of rats. Besides, chemotherapy caused cognitive impairment assessed by acetylcholinesterase activity elevation. Additionally, caspase-3 augmentation and of nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) pathway disturbance were found following chemotherapy treatment. Silymarin treatment opposed such effects via enhancing memory function, preserving brain architecture, and reducing acetylcholinesterase activity and caspase-3 level. Moreover, silymarin treatment improved mitochondrial biogenesis through activation Nrf-2/HO-1 axis. Collectively, silymarin nanoemulsion, at a 200-fold lower dose, can offer an innovative solution for cancer patients globally.

Formulation and optimization of xanthohumol loaded solid dispersion for effective treatment of Parkinson's disease in rats: In vitro and in vivo assessment

Xanthohumol (XH) is a prenylated flavonoid that possesses neuroprotective effects by increasing the levels of dopamine (DA), reducing oxidative stress, and neuroinflammation against Parkinson's disease (PD). However, the neuroprotective efficacy of XH in managing PD is limited by its low solubility, poor bioavailability, and less blood-brain barrier (BBB) permeability leading to decreased therapeutic activity. To overcome these limitations, XH-loaded solid dispersion (SD) has been formulated using the Central Composite Design (CCD) approach. The optimized formulation was evaluated by determining the angle of repose, drug loading, percentage drug release, PXRD, DSC, FTIR, and SEM. The results of PXRD, DSC, and SEM demonstrated the formation of SD. The XH-SD showed a 6.45-fold enhancement in dissolution rate, a 12.7-fold increase in Cmax, and 26.11-fold increase in XH's area under curve (AUC) as compared to the naïve XH. In the pharmacokinetic studies, XH-SD showed a 42.20 folds increase in relative bioavailability(0-∞) compared to naïve XH. To assess pharmacodynamic effects, PD was induced using rotenone. The motor and non-motor functions were evaluated by assessing various behavioral parameters such as catalepsy, spontaneous locomotor activity and muscle coordination test. The formulation exhibited dose-dependent effects, with both low and high doses of XH-SD resulting in significant enhancements (P < 0.001) in motor functions in rats induced with PD. Furthermore, biochemical estimations showed that XH-SD at both doses increased the levels of dopamine (DA), and reduced oxidative stress and neuroinflammation.

Effects of Vitamin C on Aluminum Chloride- Induced Neurotoxicity on the Hippocampal Cortex of Adult Wistar Male Rats

This study aimed to evaluate the neuroprotective effects of Vitamin C on aluminum chloride (AlCl₃)- induced brain damage, focusing on behavioral, biochemical, and histomorphological outcomes in a rodent model. Study Design: A total of 42 healthy male rats were randomly assigned to three groups: control, AlCl₃ -only, and AlCl₃ plus Vitamin C (500 mg/kg and 1000 mg/kg). The AlCl₃ groups received daily doses of AlCl₃, while the Vitamin C groups received concurrent Vitamin C supplementation. Methodology: Body weight, behavioral changes, biochemical markers of oxidative stress (MDA, SOD, GSH), and inflammation (TNF-α, IL-6) were assessed. Histomorphological analysis of the hippocampus was performed to evaluate structural damage. Behavioral assessments included locomotor and exploratory activity tests. Biochemical analyses measured oxidative stress and antioxidant enzyme activities. Results: AlCl₃ administration resulted in significant body weight loss, increased oxidative stress (elevated MDA, and SOD levels), and heightened inflammation (elevated TNF-α and IL-6). Behavioral tests showed increased excitatory activities, and increased anxiety levels as seen in increased rearing and grooming activities. Histomorphological examination revealed significant hippocampal damages as seen in the pale staining, shrunken pyramidal cells. Vitamin C co- administration mitigated these adverse effects, demonstrating reduced body weight loss, lower oxidative stress, decreased inflammation, and improved behavioral performance. Histological analysis indicated less hippocampal damage in the Vitamin C treated groups. Conclusion: As an antioxidant, Vitamin C effectively attenuates the neurotoxic effects of AlCl₃ by reducing oxidative stress and inflammation, and by protecting the hippocampal cellular integrity. These findings suggest that Vitamin C holds potential as a therapeutic agent for mitigating neurotoxicity induced by aluminum compounds.

Anti-viral Effects of Pavetta indica Methanolic Extract and Acyclovir on Behavioral and Biochemical Parameters in Streptozotocin-induced Alzheimer's Disease in Rats.

Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in β-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin. Wistar rats received acyclovir and Pavetta indica methanolic extract orally at different dose ranges (50, 150, 450 mg/kg) and (125, 250, 500 mg/kg), respectively. The standard therapy, Rivastigmine (2 mg/kg), was given orally. Intracerebroventricular-streptozotocin produced significant alternations in behavioral assessments, including locomotor activity test, Morris water maze test, and elevated plus maze test. Moreover, intracerebroventricular-streptozotocin ameliorated the antioxidant defense activity by decreasing levels of catalase, superoxide dismutase, and reduced glutathione while enhancing the oxidative stress markers, including malondialdehyde, and total nitrite levels. Finally, the main findings showed that intracerebroventricular-streptozotocin significantly increased the inflammatory marker, tumor necrosis factor-α, and disturbed neurotransmitter mediators, including levels of acetylcholinesterase, glutamate, and γ-amino butyric acid. In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the μ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine.Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine.In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Antidepressant effects of selective adenosine receptor antagonists targeting the A1 and A2A receptors administered jointly with NMDA receptor ligands: behavioral, biochemical and molecular investigations in mice

BackgroundThe objective of the study was to ascertain the antidepressant potential of the co-administration of NMDA receptor ligands and selective adenosine A1 and A2A receptor antagonists.MethodsThe forced swim test (FST) and spontaneous locomotor activity test were carried out in adult male naïve mice. Before the behavioral testing, animals received DPCPX (a selective adenosine A1 receptor antagonist, 1 mg/kg) or istradefylline (a selective adenosine A2A receptor antagonist, 0.5 mg/kg) in combination with L–701,324 (a potent NMDA receptor antagonist, 1 mg/kg), D–cycloserine (a partial agonist at the glycine recognition site of NMDA receptor, 2.5 mg/kg), CGP 37849 (a competitive NMDA receptor antagonist, 0.3 mg/kg) or MK–801 (a non-competitive NMDA receptor antagonist, 0.05 mg/kg). Additionally, serum BDNF level and the mRNA level of the Adora1, Comt, and Slc6a15 genes in the murine prefrontal cortex were determined.ResultsThe obtained results showed that DPCPX and istradefylline administered jointly with NMDA receptor ligands (except for DPCPX + D–cycloserine combination) produced an antidepressant effect in the FST in mice without enhancement in spontaneous motility of animals. An elevation in BDNF concentration was noted in the D–cycloserine-treated group. Adora1 expression increased with L–701,324, DPCPX + D–cycloserine, and DPCPX + CGP 37849, while D–cycloserine, CGP 37849, and MK–801 led to a decrease. Comt mRNA levels dropped with DPCPX + L–701,324, istradefylline + L–701,324/CGP 37849 but increased with D–cycloserine, MK–801, CGP 37849 and DPCPX + MK–801/ CGP 37849. Slc6a15 levels were reduced by D–cycloserine, DPCPX + L–701,324 but rose with DPCPX + CGP 37849/MK–801 and istradefylline + D–cycloserine/MK–801/CGP 37849.ConclusionOur study suggests that selective antagonists of adenosine receptors may enhance the antidepressant efficacy of NMDA receptor ligands highlighting a potential synergistic interaction between the adenosinergic and glutamatergic systems. Wherein, A2A receptor antagonists are seen as more promising candidates in this context. Given the intricate nature of changes in BDNF levels and the expression of Adora1, Comt, and Slc6a15 seen after drug combinations exerting antidepressant properties, further research and integrative approaches are crucial understand better the mechanisms underlying their antidepressant action.

Enhancement of Cognitive Function by Andrographolide-Loaded Lactose β-Cyclodextrin Nanoparticles: Synthesis, Optimization, and Behavioural Assessment.

This study investigates whether Andrographolide-loaded Lactose β-Cyclodextrin (ALN-βCD) nanoparticles enhance cognitive function, particularly spatial learning and memory. The successful conjugation of lactose to β-cyclodextrin was confirmed via 1H NMR spectroscopy, facilitating neuronal cell entry. The solvent evaporation method was used to create the nanoparticles, which were characterised for particle size, PDI, zeta potential, and drug release. The nanoparticles exhibited a size of 247.9 ± 3.2 nm, a PDI of 0.5 ± 0.02, and a zeta potential of 26.8 ± 2.5 mV. FTIR and TEM analyses, along with in vitro drug release and BBB permeability studies, confirmed their stability and efficacy. Behavioural tests, including the Elevated Plus Maze, Y-Maze, Object Recognition, and Locomotor Activity tests, demonstrated significant improvements in memory, motor coordination, and exploration time in the nanoparticle-treated groups. The group treated with ALN-βCD at a dose of 100 mg/kg/p.o. showed superior cognitive performance compared to the group receiving free andrographolides (AG). Biochemical assays indicated a significant reduction in acetylcholinesterase activity and lipid peroxidation, suggesting increased acetylcholine levels and reduced oxidative stress. Histopathological examination showed improved neuronal function without toxicity. The results showed significant improvements (p < 0.001) in memory and cognitive abilities in experimental animals, highlighting the potential of ALN-βCD nanoparticles as a non-invasive treatment for memory loss. These promising findings warrant further exploration through clinical trials.

Exploring the role of environmental enrichment and early life adversity on emotional development

Early life adversity has been linked with a higher probability of developing behavioral impairments and environmental manipulation is a strategy that may reduce the negative effects of exposure to adversity in early life. Here, we focused on exploring the influence of environmental enrichment (EE) as a protective factor in the context of early life adversity. We hypothesized that 24 hours of maternal deprivation (MD), in the second week of life, could induce anxiety-like behavior alterations and that exposure to EE could induce resilience to these behaviors due to alterations in the serotonergic system. Male Wistar rats were exposed to MD, on postnatal days 11 and 13, and to EE, after weaning. In adulthood, we performed a series of behavioral tests for fear, anxiety, and locomotor activity. We also measured the levels of serotonin in the amygdala and dorsal raphe nucleus. Our results revealed that MD does not impact fear behavior or the levels of serotonin, while EE decreases locomotor activity in a novel environment and enhances exploration in the predator odor test. EE also decreases serotonin in the amygdala and increases its turnover rate levels. Our findings provide insights into the critical timeframe during which stress exposure impacts the development and confirm that exposure to EE has an independent and protective effect for anxiety-like behaviors later in life.

No evidence that post-training dopamine D2 receptor agonism affects fear generalization in male rats.

The neurotransmitter dopamine plays an important role in the processing of emotional memories, and prior research suggests that dopaminergic manipulations immediately after fear learning can affect the retention and generalization of acquired fear. The current study focuses specifically on the role of dopamine D2 receptors (D2Rs) regarding fear generalization in adult, male Wistar rats, and aims to replicate previous findings in mice. In a series of five experiments, D2R (ant)agonists were injected systemically, immediately after differential cued fear conditioning (CS+ followed by shock, CS- without shock). All five experiments involved the administration of the D2R agonist quinpirole at different doses versus saline (n = 12, 16, or 44 rats/group). In addition, one of the studies administered the D2R antagonist raclopride (n = 12). One day later, freezing during the CS+ and CS- was assessed. We found no indications for an effect of quinpirole or raclopride on fear generalization during this drug-free test. Importantly, and contradicting earlier research in mice, the evidence for the absence of an effect of D2R agonist quinpirole (1 mg/kg) on fear generalization was substantial according to Bayesian analyses and was observed in a highly powered experiment (N = 87). We did find acute behavioral effects in line with the literature, for both quinpirole and raclopride in a locomotor activity test. In contrast with prior studies in mice, we have obtained evidence against a preventative effect of post-training D2R agonist quinpirole administration on subsequent fear generalization in rats.

Repeated Sulforaphane Treatment Reverses Depressive-like Behavior and Exerts Antioxidant Effects in the Olfactory Bulbectomy Model in Mice.

Growing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN. The OB model induced hyperactivity in mice during the OFT and LA as well as a temporary loss of self-care and motivation in the ST. The repeated administration of SFN (10 mg/kg) effectively reversed these behavioral changes in OB mice across all tests. Additionally, a biochemical analysis revealed that SFN (10 mg/kg) increased the total antioxidant capacity in the frontal cortex and serum of the OB model. Furthermore, SFN (10 mg/kg) significantly enhanced superoxide dismutase activity in the serum of OB mice. Overall, the present study is the first to demonstrate the antidepressant-like effects of repeated SFN (10 mg/kg) treatment in the OB model and indicates that these benefits may be linked to improved oxidative status.

Ido2 Deficiency Exacerbates Motor Impairment and Reduces Aryl Hydrocarbon Receptor Activity through Decreased Kynurenine in a Chronic Demyelinating Mouse Model.

Demyelinating diseases including multiple sclerosis (MS) are chronic inflammatory diseases of the central nervous system. Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified as catalytic enzyme involved in the rate-limiting step of the tryptophan-kynurenine pathway that influences susceptibility to inflammatory diseases. However, the pathological role of Ido2 in demyelination remains unclear. In this study, we investigated whether Ido2 deficiency influences the pathogenesis of proteolipid protein transgenic (Plp tg) mice, an animal model of chronic demyelination. Ido2 deficiency exacerbates impairments of motor function in the locomotor activity test, wire hanging test, and rotarod test. Ido2 deficiency caused severe demyelination associated with CD68-positive microglial activation in Plp tg mice. In the cerebellum of Plp tg mice, Ido2 deficiency significantly increased the expression of Tnfα. Ido2 deficiency reduced tryptophan metabolite kynurenine (KYN) levels and subsequent aryl hydrocarbon receptor (AhR) activity, which play an important role in anti-inflammatory response. These results suggest that Ido2 has an important role in preventing demyelination through AhR. Taken together, Ido2 could be a potential therapeutic target for demyelinating diseases.

In-vivo evaluation of neuroprotective effect of Chinese plant calendula officinalis Linn. Flower Extract against Aluminium chloride-induced Alzheimer's in Wistar rats

ObjectiveTo investigate the neuroprotective properties of Calendula Officinalis Linn. flower extract (COE) against mild cognitive decline and cognitive dysfunction induced by aluminium chloride (AlCl3) in experimental rats. MethodologyCOE (100, 200, and 300 mg/kg p.o.) was given once daily following the treatment of AlCl3 (100 mg/kg p.o.) to male Wistar rats for 20 days. On the 1st, 10th, and 20th days, the walking track test, locomotor activity, and object recognition test were used as behaviour characteristics to assess spatial and non-spatial memory. On the 21st day, animals were sacrificed and brains removed for biochemical and histopathological analysis. ResultsCalendula officinalis Linn. extract significantly attenuated the AlCl3-induced alterations in body weight, and motor coordination such as locomotion, stride length, and object recognition parameters. COE also reduced oxidative stress by increasing GSH, catalase, SOD, and decreasing TBARS levels. Calendula officinalis Linn. extract high dose showed most prominent therapeutic effects. P < 0.05 and mean ± SD were used to compare mean values with normal control, disease control, and high doses of Calendula officinalis Linn. extract. DiscussionBased on our study, oxidative stress has been proposed as a mechanism for AlCl3-induced neurotoxicity. We conclude that Calendula officinalis Linn. flower extract substantially decreased oxidative stress and behavioural alterations in rats treated with aluminium chloride. Calendula officinalis flowers may provide significant neuroprotective effects, potentially improving memory and learning abilities. Calendula officinalis Linn flower extract contains anti-inflammatory and antioxidant effects that might be responsible for its neuroprotective properties.

Effect of methylglyoxal on Parkinson’s disease pathophysiology in the rotenone model

Objective: Type 2 diabetes mellitus patients have been reported to have a higher incidence of Parkinson’s disease. This study aimed to explore the effect of advanced glycation end products precursor methylglyoxal (MGO) on the pathophysiology of Parkinson’s disease in a rotenone model. Materials and Methods: Adult female Wistar rats (n=42) were divided into four groups. Rotenone toxicity was assessed by daily weight measurements and mortality rates. Effect of MGO on blood glucose was evaluated. Locomotor activity, rearing, and rotarod tests were performed to evaluate motor functions, and for neurodegeneration, tyrosine hydroxylase immunoreactivity in the striatum and substantia nigra regions was assessed. Results: The mortality rate was 9% in the rotenone-applied rats. The mean weight, locomotor activity, rearing activity, and longest time spent on a rotarod were lower in the MGO+Rotenone group than in the Control group. Tyrosine hydroxylase immunoreactivity in the striatum rostral to the anterior commissure in the MGO+Rotenone group was lower than that in the Control and MGO groups. The number of tyrosine hydroxylase positive cells in the substantia nigra pars compacta was comparable among the groups. Conclusion: When nigrostriatal degeneration was triggered, MGO was found to worsen motor dysfunction and increase damage to dopaminergic neuron projections.

Effects of a Functional Food Made with Salvia hispanica L. (Chia Seed), Amaranthus hypochondriacus L. (Amaranth), and an Ethanolic Extract of Curcuma longa L. (Curcumin) in a Rat Model of Childhood Obesity.

Obesity is a global health problem and is increasing in prevalence in most countries. Although obesity affects all age groups, children are the most vulnerable sector. Functional foods are novel formulated foods containing substances (i.e., nutrients, phytochemicals, probiotics, etc.) that have potential health-enhancing or disease-preventing value. The research objective was to study the possible beneficial effects of providing a functional food made with amaranth flour, chia seed, and curcumin extract on the metabolism and behavior of a rat model of childhood obesity. Male Wistar rat pups from two litters of different sizes, a normal litter (NL) (10 pups) and a small litter (SL) (4 pups), were used. After weaning, the rats were fed a hypercaloric diet (HD) or an HD supplemented with the functional food mixture. Body weight and energy intake were measured for seven weeks, and locomotor activity, learning, and memory tests were also performed. At the end of the experiment, glucose and lipid metabolism parameters were determined. The results showed that in this model of obesity produced by early overfeeding and the consumption of a hypercaloric diet, anxiety-like behaviors and metabolic alterations occurred in the rat offspring; however, the provision of the functional food failed to reduce or prevent these alterations, and an exacerbation was even observed in some metabolic indicators. Interestingly, in the NL rats, the provision of the functional food produced some of the expected improvements in health, such as significant decreases in body weight gain and liver cholesterol and non-significant decreases in adipose tissue and leptin and insulin serum levels.

Concurrent exposure to light and traffic noise pollution augments behavioral deficits in rats: Protective effect of curcumin

The current study was aimed to explore the effect of light and traffic noise pollution exposure on behavioral and neurochemical deficits in adult male Wistar rats. We hypothesized that exposure to these pollutants alone or in combination may cause behavioral deficits in rats. Animals were allocated into different groups and were exposed to either varying light cycles (150 lx-5 lx, 14:10 h) or traffic noise with sound level 100 dBA for 6 h/day or both for 28 days. Concurrently, Curcumin (100 mg/kg; per oral; 28 days) was administered in varying light cycles and noise exposed animal groups to study the preventive effect. After the exposure time, the Morris water maze test, elevated plus maze test, novel object recognition test, locomotor activity test, and forced swimming test were conducted. The neurobehavioral results suggested that only combined exposure of light and noise pollution markedly impaired the learning as well as spatial and reference memory in rats. Furthermore, we found significant anxiety (less no. of open arm entries in EPM) and depressive-like behavior (increased immobility time) in light or/and traffic noise pollution exposed group animals in comparison to normal control groups. Curcumin treatment significantly prevented the behavioral anomalies in combined light and noise exposed rats. Furthermore, our results revealed augmentation of acetylcholinesterase, oxidative stress markers and interleukin (IL)-1β in the hippocampal region of noise and light-exposed groups which were markedly ameliorated by curcumin. In conclusion, our results suggest that curcumin significantly modulates light and noise pollution exposed behavioral and neurochemical anomalies in rats.

LRP1 in GABAergic neurons is a key link between obesity and memory function

ObjectiveLow-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood–brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. MethodsMice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory. This study evaluated the relationships between behavior and metabolic risk factors and followed the mice at 16 and 32 weeks of age. ResultsDeletion of LRP1 in GABAergic neurons caused a significant impairment in memory function in 32-week-old mice. In the spatial Y-maze test, Vgat-Cre; LRP1loxP/loxP mice exhibited decreased travel distance and duration in the novel arm compared with controls (LRP1loxP/loxP mice). In addition, GABAergic neuron-specific LRP1-deficient mice showed a diminished capacity for performing learning and memory tasks during the water T-maze test. Moreover, reduced freezing time was observed in these mice during the contextual and cued fear conditioning tests. These effects were accompanied by increased neuronal necrosis and satellitosis in the hippocampus. Importantly, the distance and duration in the novel arm, as well as the performance of the reversal water T-maze test, negatively correlated with metabolic risk parameters, including body weight, serum leptin, insulin, and apolipoprotein J. However, in 16-week-old Vgat-Cre; LRP1loxP/loxP mice, there were no differences in the behavioral tests or correlations between metabolic parameters and cognition. ConclusionsOur findings demonstrate that LRP1 from GABAergic neurons is important in regulating normal learning and memory. Metabolically, obesity caused by GABAergic LRP1 deletion negatively regulates memory and cognitive function in an age-dependent manner. Thus, LRP1 in GABAergic neurons may play a crucial role in maintaining normal excitatory/inhibitory balance, impacting memory function, and reinforcing the potential importance of LRP1 in neural system integrity.

Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.

The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.

Oxidative damage analysis and cell viability of Drosophila melanogaster exposed to three different endodontic sealers: an in vivo and ex vivo study.

The aim of this work was to evaluate the toxicological action of AH Plus (AHP), Bio-C Sealer (BCS), and EndoSequence BC Sealer (ESB), using Drosophila melanogaster as the model organism performing in vivo and ex vivo analysis. D. melanogaster were exposed for 10days to three concentrations (5mg/ml, 10mg/ml, and 20mg/ml) of AHP, BCS, and ESB sealers mixed with 10ml of standard diet. During this period, the mortality of flies was evaluated. On the 11th day, the locomotor activity test was performed and the flies were euthanized for oxidative damage analysis (reactive species and lipid peroxidation) and cell viability (resazurin reduction). For the mortality curves evaluation, the log-rank test (Mantel-Cox) was used. For the analysis of other data, a one-way analysis of variance (ANOVA) was applied, followed by Tukey's post hoc test (α = 0.05). Regarding mortality, there were no significant differences. The locomotor activity was reduced, mainly in the two highest concentrations of AHP and BCS. Besides, reactive species generation was bigger in the AHP 20mg/ml group. AHP induced a lipid peroxidation increase in all three concentrations tested, when compared to other sealers. Considering cell viability, the two highest concentrations of AHP reduced this parameter; while in other sealers, viability was reduced only in the highest concentration. AHP showed changes in oxidative markers that led to greater damage to the flies.

A high salt intake in early life affects stress-coping response in males but not in female rats

Eating diets high in salt has been associated with alterations in the immune system and the potential development of neuropsychiatric disorders. This area of research shows promise, but there is currently a limited amount of research on this topic. The present study investigated whether a high salt diet (HSD) affects anhedonia and stress-coping response behaviors in young male and female Wistar rats. In this study, male and female Wistar rats were fed an HSD (8 % NaCl w/w) from weaning to post-natal day (PND) 64. From PND 60 to 64, the rats underwent a spontaneous locomotor activity test (SLA), sucrose splash test (SST), sucrose preference test (SPT), and forced swim test (FST), followed by euthanasia at PND 65. Male and female rats consuming the HSD exhibited an increase in water intake compared to the corresponding control diet (CD) groups. Male rats had lower body weight despite having similar food intakes compared to the CD group. Male rats displayed an active stress-coping behavior in the FST, characterized by increased mobility. Additionally, HSD-fed males exhibited a greater preference for sucrose solution in the SPT. However, no effect of diet and sex were detected in the SST and the SLA, and hypothalamic levels of leptin and ghrelin receptors. On the other hand, female rats were less susceptible to the experimental conditions applied in this protocol than males.