Step-through Latency Research Articles

Evaluation of <i>Saussurea lappa</i> on Oxidative Stress and Cognition in Aluminium-induced Alzheimer’s Disease Rats

Background: Oxidative stress and neurodegenerative illnesses, such as Alzheimer's disease (AD), are closely associated. There has been a lot of thought put into finding medicinal plants with nootropic properties to slow the onset and course of AD. Objective: The study aimed to evaluate the methanolic extract of Saussurea lappa clarke (MESC) on oxidative stress and cognitive ability induced by aluminium exposure. Methods: Wistar albino rats were chosen for the study. About 30 animals were selected and grouped into 5 with 6 animals in each group. Group I served as control, group II served as disease induced (Aluminium-induced), group III, IV and V were administered with standard drug – Donepezil Hcl, and MESC at two doses – 200 and 400 mg/kg. The behavioural studies were examined by using certain apparatus like Passive Avoidance (PA) test, Elevated Plus Maze, Y- Maze and Actophotometer. Determination of anti-oxidant enzymes – Catalase (CAT) and thiobarbituric acid reactive substances (TBARS) along with acetylcholinesterase (AChE) levels which was done in rat’s brain homogenate. Results: In the PA test, administration of MESC at doses of 200 and 400 mg/kg significantly (**p< 0.01) lengthened step-through latency (STL) in rats on day 30 compared to the positive control group. Animals at MESC (200 & 400 mg/kg) showed noticeably higher memory retention (MR) rates as compared to the disease-control group. Additionally, administration of MESC (200 and 400 mg/kg) significantly (**p< 0.01) raised CAT and declined the concentration of TBARS. AChE concentration was significantly (**p< 0.01) reduced at the dose of MESC at 200 and 400 mg/kg as compared to the positive control group. Conclusion: The present study showed that MESC had a strong nootropic effect on brain antioxidant indicators and cognitive function in rats exposed to aluminium-induced oxidative stress and cognitive impairment. These findings may be investigated in the treatment of neurodegenerative diseases, including AD.

Neuroprotective Properties of Rutin Hydrate against Scopolamine-Induced Deficits in BDNF/TrkB/ERK/CREB/Bcl2 Pathways.

Background/Objectives: Alzheimer's disease (AD) is an age-related degenerative brain disorder characterized by a progressive decline in cognitive function and memory. This study aimed to evaluate whether rutin hydrate (RH) has neuroprotective effects in an AD-like learning and memory impairment rat model induced by scopolamine (SCO). Methods: The rats were administered with RH (100 mg/kg) and SCO (1.5 mg/kg) and underwent behavioral tests, including the Morris water maze test, Y-maze test, and passive avoidance test, to evaluate their learning and memory abilities. Additionally, long-term potentiation (LTP) was induced to observe changes in the field excitatory postsynaptic potential (fEPSP) activity. Results: RH treatment attenuated the SCO-induced shortening of step-through latency in the passive avoidance (PA) test, increased the percentage of alternation in the Y-maze, and increased the time spent in the target zone in the Morris water maze (MWM). Moreover, RH increased the total activity of fEPSP following theta burst stimulation and attenuated the SCO-induced blockade of fEPSP. RH also ameliorated the SCO-induced decrease in the expression levels of the BDNF, TrkB, ERK, CREB, and Bcl-2 proteins and the increase in the Bax protein level in the rat hippocampus. This demonstrates that RH has beneficial neuroprotective effects in the brain, improving learning, memory, and synaptic plasticity in rats. Conclusions: Our results highlight the molecular and cellular mechanisms through which RH exerts its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders. RH could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD.

MLR-1023 Improves Cognition Deficiency and Oxidative Stress in Lipopolysaccharide-Induced Mice Model of Alzheimer’s Disease: Role of PPAR-gamma Receptors and NO-cGMP-KATP Channels Pathway

Background: This study investigates the effects of MLR-1023 on cognitive deficiency and oxidative stress in a lipopolysaccharide (LPS)-induced mouse model. Objectives: The role of PPAR-gamma receptors and the NO- cyclic GMP (cGMP)-KATP channel pathway were examined to identify the likely mechanisms. Methods: The model was established by LPS injection. Behavioral assays included shuttle box and Y-maze tests. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were then measured in hippocampal tissue. To explore the probable mechanisms, the mice were pre-treated with agonists and antagonists 15 minutes before MLR-1023 (20 - 40 mg/kg, i.p.) administration. Results: Lipopolysaccharide increased the initial latency (IL) time, while MLR-1023 (40 mg) reduced it. Administration of L-NAME, methylene blue, and glibenclamide with MLR-1023 increased IL duration, while L-arginine, sildenafil, and diazoxide reduced it. Lipopolysaccharide reduced the duration of step-through latency (STL), whereas MLR-1023 increased it. L-NAME, methylene blue, and glibenclamide with MLR-1023 reduced STL duration, but L-arginine, sildenafil, and diazoxide increased it. The spontaneous alternation index decreased with LPS, while MLR-1023 increased it. L-NAME, methylene blue, glibenclamide, and GW9662 decreased this index, whereas L-arginine, sildenafil, diazoxide, and pioglitazone increased it. Lipopolysaccharide increased MDA concentration, while MLR-1023 decreased it. L-NAME, methylene blue, and glibenclamide increased MDA concentration, while L-arginine, diazoxide, and pioglitazone decreased it. Lipopolysaccharide reduced SOD activity, which was improved by MLR-1023. L-NAME, methylene blue, glibenclamide, and GW9662 decreased SOD activity, while sildenafil and pioglitazone increased it. Conclusions: MLR-1023 can improve LPS-induced learning-memory impairment and oxidative stress. The KATP/cGMP/NO pathway and PPARγ receptors are involved in this effect.

Investigating the Effect of Cumin (Cuminum cyminum L.) Hydroalcoholic Extract on the Incidence of Passive Avoidance Learning in Gonadectomized Male Wistar Rats

Background: Learning and memory are fundamental to the survival of human life. In view of that, a relationship exists between age-related forgetfulness and changes in sex hormone levels. Objectives: Respecting the benefits of cumin (Cuminum cyminum L.) for sex hormones, this study investigated the effect of cumin hydroalcoholic extract (HAE) on learning and memory in gonadectomized (GDX) male Wistar rats. Methods: First, cumin seeds were purchased and identified by the herbarium affiliated with Islamic Azad University (IAU), Qom branch, Qom, Iran. The hydroalcoholic extract (HAE) was then extracted using a Soxhlet apparatus, and cumin powder was prepared using a drying oven. A total of 48 male Wistar rats (weighing 250 ± 50 g) were divided into eight groups: A normal group treated with dimethyl sulfoxide (DMSO), three normal groups receiving cumin HAE doses of 25, 50, and 100 mg/kg, a GDX group treated with DMSO, and three GDX groups receiving cumin HAE doses of 25, 50, and 100 mg/kg. Following the surgical procedure to remove both testes, intraperitoneal (IP) injections were administered. Half an hour later, learning and memory tasks were conducted using the Shuttle box, and the step-through latency (STL) as the standard index of passive avoidance learning (PAL) was recorded for 10 minutes. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test. Results: The GDX male Wistar rats receiving DMSO experienced a significant decline in STL compared to the normal group treated in the same manner (P < 0.001). The rats in the GDX groups receiving cumin HAE doses of 50 and 100 mg/kg also demonstrated a significant increase in STL compared to the GDX group treated with DMSO (P < 0.001). Conclusions: As evidenced, GDX decreased PAL, but cumin HAE boosted learning and memory in the GDX male Wistar rats.

The Protective Effects of Pistacia Atlantica Gum in a Rat Model of Aluminum Chloride-Induced Alzheimer's Disease via Affecting BDNF and NF-kB.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of Pistacia atlantica gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl3). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of P. atlantica gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl3 group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl3 exposure. Our findings suggest that P. atlantica gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.

High-dose Agomelatine Combined with Haloperidol Decanoate Improves Cognition, Downregulates MT2, Upregulates D5, and Maintains Krüppel-like Factor 9 But Alters Cardiac Electrophysiology.

Haloperidol decanoate (HD) has been implicated in cognitive impairment. Agomelatine (AGO) has been claimed to improve cognition. We aimed at investigating the effects of HD + low- or high-dose AGO on cognition, verifying the melatonergic/dopaminergic to the cholinergic hypothesis of cognition and exploring relevant cardiovascular issues in adult male Wistar albino rats. HD + high-dose AGO prolonged the step-through latency by +61.47% (P < 0.0001), increased the time spent in bright light by +439.49% (P < 0.0001), reduced the time spent in dim light by -66.25% (P < 0.0001), and increased the percent of alternations by +71.25% (P < 0.0001), despite the reductions in brain acetylcholine level by -10.67% (P < 0.0001). Neurodegeneration was minimal, while the mean power frequency of the source wave was reduced by -23.39% (P < 0.05). Concurrently, the relative expression of brain melatonin type 2 receptors was reduced by -18.75% (P < 0.05), against increased expressions of dopamine type 5 receptors by +22.22% (P < 0.0001) and angiopoietin-like 4 by +119.18% (P < 0.0001). Meanwhile, electrocardiogram (ECG) demonstrated inverted P wave, reduced P wave duration by -36.15% (P < 0.0001) and PR interval by -19.91% (P < 0.0001), prolonged RR interval by +27.97% (P < 0.05), increased R wave amplitude by +523.15% (P < 0.0001), and a depressed ST segment and inverted T wave. In rats administered AGO, HD, or HD+ low-dose AGO, Alzheimer's disease (AD)-like neuropathologic features were more evident, accompanied by extensive ECG and neurochemical alterations. HD + high-dose AGO enhances cognition but alters cardiac electrophysiology. SIGNIFICANCE STATEMENT: Given the issue of cognitive impairment associated with HD and the claimed cognitive-enhancing activity of AGO, combined high-dose AGO with HD improved cognition of adult male rats, who exhibited minimal neurodegenerative changes. HD+ high-dose AGO was relatively safe regarding triggering epileptogenesis, while it altered cardiac electrophysiology. In the presence of low acetylcholine, the melatonergic/dopaminergic hypothesis, added to angiopoietin-like 4 and Krüppel-like factor 9, could offer some clue, thus offering novel targets for pharmacologic manipulation of cognition.

Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.

In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-β (Aβ) 25-35-induced murine model of Alzheimer's disease (AD). Aβ-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aβ load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice.

Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly (p < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less (p < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly (p < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZ-kindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.

Antidepressant-like Effects of Chinese Quince (Chaenomeles sinensis) Fruit Based on In Vivo and Molecular Docking Studies.

In this study, we examined the potential antidepressant-like effects of Chinese quince fruit extract (Chaenomeles sinensis fruit extract, CSFE) in an in vivo model induced by repeated injection of corticosterone (CORT)-induced depression. HPLC analysis determined that chlorogenic acid (CGA), neo-chlorogenic acid (neo-CGA), and rutin (RT) compounds were major constituents in CSFE. Male ICR mice (5 weeks old) were orally administered various doses (30, 100, and 300 mg/kg) of CSFE and selegiline (10 mg/kg), a monoamine oxidase B (MAO-B) inhibitor, as a positive control following daily intraperitoneal injections of CORT (40 mg/kg) for 21 days. In our results, mice treated with CSFE exhibited significant improvements in depressive-like behaviors induced by CORT. This was evidenced by reduced immobility times in the tail suspension test and forced swim test, as well as increased step-through latency times in the passive avoidance test. Indeed, mice treated with CSFE also exhibited a significant decrease in anxiety-like behaviors as measured by the elevated plus maze test. Moreover, molecular docking analysis indicated that CGA and neo-CGA from CSFE had stronger binding to the active site of MAO-B. Our results indicate that CSFE has potential antidepressant effects in a mouse model of repeated injections of CORT-induced depression.

Terminalia chebula attenuates restraint stress-induced memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala by inhibiting oxidative damage

Chronic restraint stress induces cognitive abnormalities through changes in synapses and oxidant levels in the amygdala and hippocampus. Given the neuroprotective effects of fruit of Terminalia chebula (Halileh) in different experimental models, the present investigation aimed to address whether Terminalia chebula is able to reduce chronic restraint stress-induced behavioral, synaptic and oxidant markers in the rat model. Thirty-two male Wistar rats were randomly divided into four groups as follows: control (did not receive any treatment and were not exposed to stress), stress (restraint stress for 2 h a day for 14 consecutive days), Terminalia chebula (received 200 mg/kg hydroalcoholic extract of Terminalia chebula), and stress + Terminalia chebula groups (received 200 mg/kg extract of Terminalia chebula twenty minutes before stress) (n = 8 in each group). We used the shuttle box test to assess learning and memory, Golgi-Cox staining to examine dendritic spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala, and total antioxidant capacity (TAC) and total oxidant status (TOS) in the brain. The shuttle box test results demonstrated that Terminalia chebula treatment had a profound positive effect on memory parameters, including step-through latency (STL) and time spent in the dark room, when compared to the stress group. Daily oral treatment with Terminalia chebula effectively suppressed the loss of neural spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala caused by chronic restraint stress, as demonstrated by Golgi-Cox staining. Additionally, the results indicate that Terminalia chebula significantly reduced the TOS and increased TAC in the brain compared to the stress group. In conclusion, our results suggest that Terminalia chebula improved memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala induced by restraint stress via inhibiting oxidative damage.

LC-qTOF-MS/MS phytochemical profiling of Tabebuia impetiginosa (Mart. Ex DC.) Standl. leaf and assessment of its neuroprotective potential in rats

Ethnopharmacological relevanceTabebuia impetiginosa (Bignoniaceae) was traditionally used for memory enhancement and central nervous system (CNS) stimulation.Aim of the study: This study aims to create a metabolic profile of the ethyl acetate fraction of T. impetiginosa (TEF) and investigate for the first time its neuroprotective potential on cyclophosphamide (CP)-induced chemobrain, validating its traditional use. Materials and methodsMetabolite profiling of TEF was performed using Liquid Chromatography coupled with Quadrupole Time of Flight-Mass/Mass Spectrometry (LC-qTOF-MS/MS). For the in vivo study, CP (200 mg/kg, i.p.) was administered to induce cognitive impairment in rats; TEF (30 mg/kg, p.o.) was administered throughout the 14 days of the experiment to assess its role in mitigating CP-induced neuronal deficits. Behavioral tests including locomotor, Y-maze, and passive avoidance tests were conducted. Additionally, biochemical markers such as reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and caspase-3 immunoexpression were assessed in the hippocampus area. ResultsForty-four phytoconstituents were tentatively identified in TEF, mainly iridoids and organic acids. TEF showed significant memory enhancement as evidenced by the increase in step-through latency in the passive avoidance test by 1.5 folds and the increase in sequence alternation percentage (SAP) in the Y-maze test by 67.3%, as compared to CP-group. Moreover, it showed pronounced antioxidant and anti-inflammatory potentials evidenced by the significant elevation in reduced glutathione (GSH) levels by 80% and a pronounced decline in MDA and TNF-α levels by 24% and 45%, respectively relative to the CP group. TEF treatment restored normal hippocampal histological features and attenuated apoptotic caspase-3 expression by 70% compared to the CP group. ConclusionsTEF can act as a promising natural scaffold in managing the chemobrain induced by CP in cancer patients.

Agmatine alleviates ethanol withdrawal-associated cognitive impairment and neurochemical imbalance in rats

The present study aimed to investigate the role of agmatine in the neurobiology underlying memory impairment during ethanol withdrawal in rats. Sprague-Dawley rats were subjected to a 21-day chronic ethanol exposure regimen (2.4 % w/v ethanol for 3 days, 4.8 % w/v for the next 4 days, and 7.2 % w/v for the following 14 days), followed by a withdrawal period. Memory impairment was assessed using the passive avoidance test (PAT) at 24, 48, and 72 h post-withdrawal. The ethanol-withdrawn rats displayed a significant decrease in step-through latency in the PAT, indicative of memory impairment at 72 h post-withdrawal. However, administration of agmatine (40 µg/rat) and its modulators (L-arginine, arcaine, and amino-guanidine) significantly increases the latency time in the ethanol-withdrawn rats, demonstrating the attenuation of memory impairment. Further, pretreatment with imidazoline receptor agonists enhances agmatine's effects, while antagonists block them, implicating imidazoline receptors in agmatine's actions. Neurochemical analysis in ethanol-withdrawn rats reveals dysregulated glutamate and GABA levels, which was attenuated by agmatine and its modulators. By examining the effects of agmatine administration and modulators of endogenous agmatine, the study aimed to shed light on the potential therapeutic implications of agmatinergic signaling in alcohol addiction and related cognitive deficits. Thus, the present findings suggest that agmatine administration and modulation of endogenous agmatine levels hold potential as therapeutic strategies for managing alcohol addiction and associated cognitive deficits. Understanding the neurobiology underlying these effects paves the way for the development of novel interventions targeting agmatinergic signaling in addiction treatment.

Effects of extracts and manna of Echinops cephalotes on impaired cognitive function induced by scopolamine in mice.

Alzheimer's disease (AD) is a neurodegenerative disease specified by chronic and irreversible destruction of neurons. This study aimed to evaluate the effects of different extracts (aqueous, hydroalcoholic, hexane, and ethyl acetate) and manna of Echinops cephalotes (EC) on impaired cognitive function induced by scopolamine in mice. EC is shown to have anti-cholinesterase-butyrylcholinesterase activities. In this study, aqueous and hydroalcoholic extracts, hexane and ethyl acetate fractions of EC (25, 50, 100 mg/kg, i.p.), and the manna (25, 50, 100 mg/kg, gavage) were administered for 14 days alongside scopolamine (0.7 mg/kg, i.p.). Rivastigmine (reference drug) was administered for 2 weeks i.p. Mice were tested for their memory function using two behavioral models, object recognition test (ORT) and passive avoidance test (PAT). Administration of scopolamine significantly impaired memory function in both behavioral models. In the PAT model, all extracts at 50 and 100 mg/kg significantly reversed the effect of memory destruction caused by scopolamine. At a lower dose of 25 mg/kg, however, none of the extracts were able to significantly change the step-through latency time. In the ORT model, however, administration of all extracts at 50 and 100 mg/kg, significantly increased the recognition index. Only the manna and the aqueous extract at 25 mg/kg were able to reverse scopolamine-induced memory impairment. These results suggest that all forms of EC extracts improve memory impairment induced by scopolamine comparably to rivastigmine. Whether the effects are sustained over a longer period remains to be tested in future work.

The dose-dependent neuroprotective effect of norepinephrine in improving memory retrieval in an experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is considered an immune-mediated inflammatory disorder that causes cognitive impairments by damaging the hippocampal tissue. Conversely, norepinephrine (NEP) has anti-inflammatory and re-myelinating properties, which improve cognitive impairments. The aim of this study was to assess the neuroprotective effects of NEP on learning and memory disorders in an experimental animal model of MS. Two guide cannulas were bilaterally implanted in the rat hippocampal CA1 regions. After recovery, the animals received 3 μl of 0.01% ethidium bromide (EtB) in each of both hippocampal regions. After three days, the rats were randomly divided into 6 groups (8 rats/group), including control, sham 1, sham 2, and three groups of NEP 0.25, 0.5, and 1 mg/kg by intrahippocampal injection. Behavioral tests (e.g. shuttle box test and open-field test) were then performed. Finally, ROS, MDA, GSH, TNF-α, IL-6, and IL-1β concentrations in the left CA1 area, as well as using western-blot analysis, p-p38, p-JNK, p-AKT, p-ERK1/2, p-NMDA, p-AMPA, p-CREB, and BDNF proteins in the right CA1 region evaluated. The EtB injection increased ROS, MDA, TNF-α, IL-6, and IL-1β levels, as well as p-JNK and p-P38, except all other proteins, while decreasing GSH content, as well as step-through latency and locomotor activity in sham groups compared to the control group. Conversely, NEP (0.5 and 1 mg/kg, particularly at the dose of 1 mg/kg) counterbalanced all the alterations mentioned above in comparison to the sham groups. The EtB induced learning and memory impairment; however, NEP dose-dependently restored these impairments to normal levels.

A Standardized Extract of Microalgae Phaeodactylum tricornutum (Mi136) Inhibit D-Gal Induced Cognitive Dysfunction in Mice.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhyt™) with different human equivalent doses to evaluate potential dose-response effects. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

Intracerebroventricular Injection of MHY1485 Blocked the Beneficial Effect of Adiponectin on Aversive Memory in the STZ Model of Dementia.

The most prominent adipokine, adiponectin (APN), has an adverse relationship with the malfunction of adipose tissue. Obesity causes a decrease in plasma APN levels, which eventually results in insulin resistance and diabetes. In this study, we assessed how the effects of APN on memory are influenced by the insulin receptor substrate-1 (IRS-1) and the mammalian target of rapamycin (mTOR) pathways. Streptozotocin (STZ) 3 mg/kg intracerebroventricular injections on days 1 and 3 following cannulation were used to create an animal model of Alzheimer's disease. The acquisition phase was preceded by injections of MHY and adiponectin. For the passive avoidance task, the stepthrough latency and total duration in the dark compartment were recorded and evaluated, and the preference index was calculated for the novel object identification test. IRS-1 protein expression in the hippocampus was assessed by western blotting. STZ reduced the step-through latency (STL), which rose significantly (P≤0.001) in the APN+STZ group. The memory-improving effects of APN were reversed when MHY was administered first (P≤0.001). The STZ and APN+STZ+MHY groups both had a substantial decline in the preference index (P≤0.01). Compared to the control group, the STZ group's expression of the IRS- 1 protein was dramatically reduced (P≤0.0001). In contrast to the APN+STZ group, the MHYtreated group likewise showed decreased IRS-1 protein expression (P≤0.0001), but APN+STZ was able to enhance IRS-1 expression rate (P≤0.0001). In a rat model of AD, we found that adiponectin improved aversive and cognitive memory, which is at least partially mediated by the mTOR signaling cascade.

Potential neuroprotective effect of nanomicellar curcumin on learning and memory functions following subacute exposure to bisphenol A in adult male rats.

Bisphenol A (BPA) is an endocrine-disrupting chemical commonly utilized in the manufacture of plastics, which may cause damage to brain tissue. Curcumin is a phytochemical with protective effects against neurological and mental diseases. The purpose of this research was to evaluate whether nanomicellar curcumin (NmCur) might protect rats against BPA-induced learning and memory deficits. After determining the proper dose of BPA, the animals were randomly divided into 8 groups (8 rats in each group) receiving dextrose 5% (as vehicle of NmCur) (Dex), sesame oil (as vehicle of BPA) (Sea), Sea plus Dex, NmCur (50mg/kg), BPA (50mg/kg), and 50mg/kg BPA plus 10, 25, and 50mg/kg NmCur groups, respectively. Behavioral tests performed using passive avoidance training (PAT), open-field (OF), and Morris water maze (MWM) tests. The expression of oxidative stress markers, proinflammatory cytokines, oxidative stress-scavenging enzymes, glutamate receptors, and MAPK and memory-related proteins was measured in rat hippocampus and cortical tissues. BPA up-regulated ROS, MDA, TNF-α, IL-6, IL-1β, SOD, GST, p-P38, and p-JNK levels; however, it down-regulated GSH, GPx, GR, CAT, p-AKT, p-ERK1/2, p-NR1, p-NR2A, p-NR2B, p-GluA1, p-CREB, and BDNF levels. BPA decreased step-through latency (STL) and peripheral and total, but not central, locomotor activity. It increased the time to find the hidden platform, the mean of escape latency time,and the traveled distance in the target quadrant, but decreased the time spent in the target quadrant. The combination of BPA (50mg/kg) and NmCur (25 and 50mg/kg) reversed all of BPA's adverse effects. Therefore, NmCur exhibited neuroprotective effects against subacute BPA-caused learning and memory impairment.

Berberine improves inhibitory avoidance memory impairment of Toxoplasma gondii-infected rat model of ketamine-induced schizophrenia

BackgroundMemory impairment caused by Toxoplasma gondii infection has been documented. Berberine (BRB) is well known for its enhancing effects on memory and has shown promising results. However, the impact of BRB on T. gondii infection and schizophrenia-induced consolidation and reconsolidation memory impairment is still unclear. Here; we examined the effect of BRB on the inhibitory avoidance (IA) memory consolidation and reconsolidation impairment induced by T. gondii infection, and ketamine (Ket) as a pharmacological model of schizophrenia. Also; the brain-derived neurotrophic factor (BDNF) levels in the medial prefrontal cortex (mPFC) and hippocampus were analyzed.MethodsRats were infected with T. gondii RH strain or received Ket (30 mg/kg/day) intraperitoneally (i.p) for at least five consecutive days (as the model of schizophrenia). Then followed by oral administration with BRB (25 mg/kg/day) for five days. Finally, the IA memory retention test was examined 48 post-conditioning, and BDNF was measured.ResultsResults indicated IA memory impairment in T. gondii-infected animals since lower step-through latency (STL) was observed than in control animals. We found significant (P = 0.01, P = 0.001) elevations in STL and a significant decrease (P = 0.001) in total time spent in the dark area following BRB administration in infected and Ket-treated rats, indicating improvement (increased STL) in consolidation and reconsolidation memory. Moreover, BDNF levels were reduced (P = 0.01) in the hippocampus and mPFC regions of both T. gondii- infected and Ket-induced groups, which remarkably enhanced after BRB treatment. Furthermore; we found that BRB administration notably increased the mPFC BDNF levels in mPFC (P < 0.01) and hippocampus (P = 0.001) in the Ket-treated and rats infected with T. gondii.ConclusionTaken together; BRB may be a valuable preclinical treatment for improving memory impairment through BDNF expression in PFC and hippocampus, therefore; BRB is suggested for memory disturbances induced by T. gondii infection.

Rosmarinic acid-rich ethanolic extract of Orthosiphon stamineus ameliorates cognitive and hippocampal long-term potentiation in chronic cerebral hypoperfusion rat model

Chronic cerebral hypoperfusion (CCH) is one of the main causes of vascular dementia caused by the reduced blood flow to the brain. Orthosiphon stamineus (OS) is a medicinal herb exhibiting pronounced neuroprotective, anti-oxidant and anti-inflammatory activities due to its high rosmarinic acid content. This study investigated the nootropic effect of OS ethanolic extract on cognitive functions in CCH rats. CCH was developed by permanent bilateral occlusion of the common carotid artery (PBOCCA). Passive avoidance task (PAT) and Morris water maze (MWM) test were conducted to evaluate cognitive functions followed by in vivo long-term potentiation (LTP) for assessing neuroplasticity. The rosmarinic acid content of OS ethanolic extract was quantified using a validated HPLC-PDA. Treatment with OS ethanolic extract significantly increased step-through latency in the PAT, decreased escape latency at a low dose of OS extract in the MWM and rescued the LTP impairment at the highest dose in CCH rats. These results strongly support the effectiveness of rosmarinic acid-rich OS extract (5.088 % w/w) in treating pathological vascular dementia caused by CCH.

Nicotinamide mononucleotide (NMN) ameliorated Nonylphenol-induced learning and memory impairment in rats via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway.

Nonylphenol (NP) exposure can trigger neurotoxicity and cause learning and memory impairment. Nicotinamide mononucleotide (NMN) has a therapeutic effect on neurodegenerative diseases, but the role of NMN on NP-induced learning and memory impairment is not known. Here, we examined the mitigative effect of NMN on the impaired learning and memory ability of rats exposed to NP. The NP impaired learning and memory in rats, while the low-dose intervention with NMN significantly prolonged the step-through latency of the PAT and improved the NAMPT and NMNAT1 content in brain tissue. At the same time, the NMN intervention also increased the content of 5-HTR1A, 5-HTR4, and 5-HTR6 related to learning and memory in the hippocampus. In line with this, we found that the NMN intervention activated the SIRT1/MAO-A pathway in brain tissue. NMN intervention, especially at 125 mg/kg doses, may improve rats' NP-induced learning and memory impairment via the central 5-HT system and the NAD+/SIRT1/MAO-A pathway in the brain.