Passive Avoidance Memory Research Articles

Maternal Separation Exhibits a Sex Dimorphism in Memory Impairments in Adolescent Rats: Acute Methylphenidate Administration as a Treatment.

Rodents are highly dependent on maternal care after birth. Disturbing mother and pup interactions leads to detrimental alternations for the rat and the mother. Maternal separation (MS) is an accepted model for investigating disruption of mother and pup relationship. In addition to other detrimental effects, MS is a model known to induce permanent changes in learning and memory. Methylphenidate has been effective in memory enhancement in individuals suffering from memory deficits, attention-deficit hyperactive disorder (ADHD), as well as healthy subjects for better performance in exams. In this research, a 21-day separation for 3 h was implemented, and the effects of MS on spatial and passive avoidance learning, and memory were evaluated in the mid-adolescence period of rats, in both males and females. Also, a drug intervention of a high therapeutic dose of 5 mg per kg was used in a five-day period in different control and MS groups. Morris water maze was utilized for spatial learning and memory analysis, and a shuttle box paradigm was used for passive avoidance learning and memory. Through our behavioral tests, we have shown that MS can alter spatial learning and memory in males. On the other hand, females are protected from the detrimental effects of MS on spatial learning and memory. Furthermore, passive avoidance learning was not different among groups, be it male or female. However, in the case of memory evaluation in the passive avoidance test, the male did not exhibit a significant difference in step-through latency. However, maternally separated females had poor performance in the memory phase with shorter step-through latencies. Methylphenidate compensated for the deleterious effects of MS on learning and spatial memory for the male group and passive avoidance memory in the female group at the behavioral level.

Impact of Parental Ethanol Exposure on Offspring Memory: Sex Differences in Spatial and Passive Avoidance Tasks.

The impact of parental alcohol exposure on subsequent generations recently gained significant attention. Ethanol, widely consumed by humans, is known for its anxiolytic effects upon initial use. However, repeated ethanol consumption leads to cognitive dysfunction, dependence, and other physical abnormalities. In line with recent publications from our group, this study investigated the role of parental ethanol exposure-10 days prior to gestation-on learning and memory, which are critical cognitive abilities, in male and female offspring. Adult male and female Wistar rats (n=12) were exposed to ethanol (in drinking water) for 30 days, followed by a 10-day ethanol-free period. Each rat was then paired to mate with either an ethanol-naïve (control, n=12) or ethanol-exposed rat, resulting in four distinct groups: (1) control male and female, (2) ethanol-exposed male and control female (P.EE), (3) ethanol-exposed female and control male (M.EE), and (4) ethanol-exposed male and female (P+M.EE). Adult male and female offspring were tested for spatial learning and memory (Morris Water Maze) and passive avoidance memory. Additionally, brain-derived neurotrophic factor (BDNF) levels in the cerebrospinal fluid were evaluated. Results showed that spatial memory was negatively affected by parental ethanol consumption in both male and female offspring, while spatial learning was impaired only in female offspring of ethanol-exposed dams. In the passive avoidance paradigm, memory retrieval was impaired in ethanol-exposed male offspring, whereas in females, only the P+M.EE group showed a deficit in memory retention. While BDNF levels decreased in male offspring, an enhancement in BDNF was observed in female offspring of the P.EE group. In conclusion, our findings suggest that parental ethanol exposure before conception has differential impacts on learning and memory, depending on the offspring's sex and the type of memory tested. Spatial memory was affected in both sexes (except for females in the P.EE group), while memory retrieval in the passive avoidance task remained unaffected in female offspring of the P.EE and M.EE groups. Conversely, male offspring of ethanol-exposed sires and dams exhibited deficits in passive avoidance memory. This may suggest that in memory tasks involving inhibitory cues, such as passive avoidance, female offspring of ethanol-exposed dams or sires are more resilient to memory deficits compared to male offspring. This resilience could possibly be attributed to their higher anxiety levels relative to males.

Effects of cypermethrin exposure on learning and memory functions and anxiety-like behavior in rats

BackgroundCypermethrin (CYP), a synthetic pyrethroid widely used to control plant pests, has been associated with various diseases in humans exposed to pesticides, either directly or indirectly. This study aimed to examine the effects of CYP on learning and memory functions, as well as anxiety-like behavior.MethodsForty male Wistar rats (8 weeks old) were randomly assigned to 4 groups: The first group served as the control, while the other three groups received different doses of CYP (5, 20, and 80 mg/kg) via gavage once daily for one month. Passive avoidance learning (PAL) and memory were assessed using the shuttle box test, cognitive memory was evaluated using the novel object recognition (NOR) test, and spatial memory was measured with the Morris water maze (MWM) test. The elevated plus-maze (EPM) and open field tests were used to assess locomotor activity and anxiety levels.ResultsIn the PAL test, significant differences were observed in the time spent in the dark compartment (TDC) and step-through latency in the retention trial (STLr) in rats receiving 80 mg/kg of CYP. MWM results indicated memory impairment in rats treated with 20 and 80 mg/kg of CYP. Additionally, rats treated with the highest dose of CYP (80 mg/kg) showed a reduction in the number of entries into the open arms of the EPM compared to the control group.ConclusionThis study demonstrates that CYP negatively affects learning and memory retention. Further research is needed to explore the precise mechanisms by which this toxin impacts cognitive functions.

Beneficial effects of fenoprofen on cognitive impairment induced by the kindling model of epilepsy: interaction of oxidative stress and inflammation

Hippocampal-dependent cognitive impairments are consequences of temporal lobe epilepsy. This study aimed to assess the modulatory effects of fenoprofen on Pentylenetetrazol (PTZ)-induced cognitive dysfunction in the rat model of epilepsy. Male Wistar rats were randomly divided into five groups. Except for the control group, the kindling model was induced by intraperitoneal (IP) injection of PTZ (35mg/kg) every other day for a month. Three groups received fenoprofen (10, 20, and 40mg/kg) before each PTZ injection. One week after kindling development, rats were challenged with PTZ (70mg/kg). The Morris Water Maze, Shuttle Box, and Elevated Plus Maze tests were applied to assess cognitive functions. Rats’ serum and brain samples were prepared for biochemical, histological, and gene expression studies. Fenoprofen pretreatment effectively reduced the mean seizure score, and treated rats had better cognitive performance than the PTZ group in passive avoidance and spatial memory and learning tests; they also showed less anxiety-like behaviors. Its administration also showed anti-oxidative properties. So the serum level of Nitric oxide was significantly reduced while Glutathione and Catalase increased significantly. It also diminished the expression of inflammatory genes (Tumor Necrosis Factor alpha (TNF-α) and Nuclear Factor Kappa B (NF-kB)) in the hippocampus, these results were confirmed by histological observation from Hematoxylin & Eosin staining. These results show the ability of fenoprofen to reduce cognitive impairments caused by epilepsy induction. These effects seem to be through the modulation of inflammatory mediators and oxidative stress.

Acute Treatment with Fucoidan Ameliorates Traumatic Brain Injury-Induced Neurological Damages and Memory Deficits in Rats: Role of BBB Integrity, Microglial Activity, Neuroinflammation, and Oxidative Stress.

There is no acquiesced remedy for the treatment of traumatic brain injury (TBI)-associated impairment, especially cognitive decline. The first 24h after TBI is a golden time for preventing the progress of the impairments. The present study aimed to examine the acute effects of fucoidan on neurological outcomes and memory performance and investigate its potential mechanisms in rats with TBI. Fucoidan (25, 50, and 100mg/kg, i.p.) was injected immediately after TBI induction. Veterinary coma scale (VCS), brain edema, blood-brain barrier (BBB) integrity, passive avoidance memory and spatial memory, neuroplasticity, myeloperoxidase (MPO) activity, oxidative stress, and histological alteration were evaluated after TBI induction and fucoidan treatment. The findings revealed that TBI resulted in an enhancement in brain water content and BBB permeability and diminished the performance of passive avoidance memory and spatial memory. These were accompanied by long-term potentiation (LTP) suppression in the hippocampus and the prevention of activities of SOD, catalase, and GPx and enhancement of MPO activity, TNF-α, IL-6, and lipid peroxidation levels in the hippocampus as well as hippocampal neuronal loss. Fascinatingly, acute treatment of TBI rats with fucoidan especially in the higher doses (50 and 100mg/kg) significantly ameliorated (p < 0.05) neurological outcomes of VCS, cerebral edema, BBB integrity, passive avoidance memory, spatial memory, LTP impairment, and oxidative-antioxidative balance. Also, fucoidan significantly ameliorated hippocampal neuronal loss, TNF-α and IL-6 levels, and MPO activity as an indicator of microglial activation. These outcomes imply that fucoidan can be a hopeful remedy for TBI-associated neuronal impairments. However, further research is necessary to endorse this issue.

The Effect of Zeolite Zinc on Memory Performance and Hippocampal Cell Death in a Rat Model of Alzheimer's-like Disease Induced by Aβ1-42.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, characterized by the slow and progressive loss of brain structure and function, primarily affecting older individuals. Evidence has shown that disruption of zinc homeostasis in the brain contributes to synaptic dysfunction, as well as impairments in learning and memory. In this study, we evaluated the effect of zeolite zinc on memory performance and hippocampal cell death in a rat model of Alzheimer's disease (AD) induced by intracerebroventricular administration of Aβ1-42. We employed the Morris water maze, shuttle box, and open field tests to assess spatial memory, passive avoidance memory, and anxiety-like behavior, respectively. P-Tau and the amyloid precursor protein (APP) expression, along with hippocampal cell death, were also evaluated. Both Aβ1-42 and zeolite zinc were injected intracerebroventricularly. The results showed that zeolite zinc partially reversed Aβ1-42-induced impairments in memory performance and mitigated the effects of Aβ1-42 on locomotor activity, although it did not fully restore baseline levels. In addition, Aβ1-42 increased the expression of APP and P-Tau, as well as the number of dead cells, whereas zeolite zinc reduced these effects. In conclusion, our findings suggest that while zeolite zinc plays a role in modulating the pathophysiology of AD, its therapeutic effects only partially reverse the progression or symptoms of AD, indicating the need for further investigation into optimal dosing or combination therapies.

Theta band optogenetic stimulation of the septo‐hippocampal fibres in the fornix reduces interictal spikes and rescues memory performance in hAPP‐j20 mice

AbstractBackgroundAltered neuronal timing and synchrony are biomarkers for Alzheimer’s disease (AD) and correlate with memory impairments. Electrical stimulation of the fornix, the main fibre bundle connecting the hippocampus to the septum, has emerged as a potential intervention to restore network synchrony and memory performance in human AD and mouse models. However, electrical stimulation is non‐specific and may partially explain why fornix stimulation in AD patients has yielded mixed results. We hypothesize that driving the specific circuits underlying rhythmicity within the fornix via optogenetics at the biologically relevant theta rhythm (5Hz) will stabilize septo‐hippocampal network timing in an AD mouse model (hAPP‐j20) to alleviate hypersynchronous interictal spikes (IS) and restore memory performance.MethodsGABAergic neurons in the septum were transfected with the excitatory opsin ChETA (or eYFP controls) in J20+/+ or J20± littermate controls. An optical fibre was placed above the fornix to limit excitation to the projection fibres and recording electrodes were placed in CA1 to measure network oscillations. 5Hz stimulation was applied continuously for 4 hours following the encoding phase of either novel‐object‐location or passive contextual avoidance memory tasks. We also combined in vivo calcium imaging with electrical recordings in CA1 to monitor network activity to determine how IS shape hippocampal cell assemblies in J20+/+ mice without fornix stimulation.ResultsInterictal spikes were present in sleep in J20+/+ mice, and at a higher rate during REM (4.78/min) compared to slow‐wave (1.76/min; n = 11, p&lt;0.001, one‐way ANOVA). J20+eYFP controls displayed a strong negative correlation between the rate of IS and memory recall score (n = 9, r = ‐0.62, p = 0.015). 5Hz optical fornix stimulation reduced the occurrence of IS in REM both during stimulation and 4hrs post‐stimulation (n = 11, p = 0.024, repeated measures ANOVA). Continuous 4‐hour theta stimulation between the encoding and recall phases of both memory tasks rescued J20+ChETA performance to levels comparable with healthy controls while J20+eYFP mice performed at the chance level (n = 9‐10 per group, p = 0.017, two‐way mixed ANOVA).ConclusionThese data validate theta band optical stimulation as a viable method to pace the septo‐hippocampal network effectively reducing IS events and recovering memory performance in an APP mouse model.

Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation

Traumatic brain injury (TBI) frequently leads to cognitive impairments. The toll-like receptor 4 (TLR4) ligand, Monophosphoryl lipid A (MPL), has shown promise in modulating neuroinflammatory responses after TBI. We investigated the effects of MPL on spatial memory, passive avoidance memory, neuronal survival, and inflammatory/anti-inflammatory cytokines in rat brain following mild-to-moderate TBI. Rats underwent a learning period in the Morris water maze and shuttle box, followed by TBI induction by controlled cortical impact. MPL was administered into the cerebral ventricle 20 min after TBI. Spatial memory was assessed 7 and 28 days later. Passive avoidance memory was assessed 2 and 6 days after TBI. MPL significantly improved the spatial memory deficit at 7 days but not 28 days after TBI. It also improved impairment of the avoidance memory at both 2 and 6 days after TBI. MPL prohibited the TBI-induced TNF-α increase and IL-10 decrease in the injured region at 7 days post-TBI period. MPL prevented the neuronal loss induced by TBI in the hippocampus. A single administration of MPL shortly after TBI alleviates short-term memory deficits, through anti-inflammatory and anti-cell loss activities. Repeated MPL administration may also inhibit the long-term memory deficits after TBI.

Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic-Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress.

A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51-53 to PND 58-60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant properties.

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease

Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila’s impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 109 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.

Can L-Methionine and S-Adenosyl-L-Methionine effectively mitigate scopolamine-induced cognitive and motor deficits in mice?

Motor balance deficits often coincide with cognitive deficits in older adults. Current medications provide temporary relief with several potential side effects. Essential amino acids and their derivatives, such as S-Adenosyl-L-Methionine (SAMe), can improve nerve function, mood regulation, and neuroprotection against neurodegenerative diseases. This study investigated the protective effects of SAMe in scopolamine-degraded memory, and motor balance in an animal model. To evaluate the possible effects of SAMe on cognitive and motor balance improvement, both Shuttle box and rotarod methods were performed in seven groups of animals (n=7). The mice groups received the saline (control), scopolamine, scopolamine+rivastigmine, scopolamine +methionine, and scopolamine+ three different doses of SAMe daily and separately for two weeks. Data were analyzed independently by one-way ANOVA and P<0.05 was considered significant. SAMe 150 mg/kg worsened scopolamine-induced memory impairment (P<0.001), while methionine (100 mg/kg) or SAMe (only 100 mg/kg) together with scopolamine could reduce the duration of the animal's presence in the dark chamber (P<0.05). Daily administration of methionine and SAMe at the rate of 100 mg/kg daily could significantly improve the decrease in motor balance caused by scopolamine (P<0.05). Rivastigmine improved memory and motor balance impairment caused by scopolamine (P<0.05). No difference between SAMe and L-methionine for memory, and balance. The results suggest that while L-methionine and SAMe may not be effective in improving memory impairments (Even SAMe high doses can aggravate the destruction of passive avoidance memory), they may be beneficial in enhancing motor balance.

Ascending Vagal Sensory and Central Noradrenergic Pathways Modulate Retrieval of Passive Avoidance Memory in Male Rats.

Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTSNA-to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

Deregulation of Melatonin Receptors and Differential Modulation of After-Hyperpolarization and Ih Currents Using Melatonin Treatment Due to Amyloid-β-Induced Neurotoxicity in the Hippocampus.

Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive-promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline- and amyloid-β 1-42 (Aβ) peptide-injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aβ-induced deficit in passive-avoidance memory. Whole-cell patch-clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aβ-injected group. Interestingly, treatment with melatonin enhances after-hyperpolarization in control, but not Aβ-injected rats. In contrast, our voltage-clamp study showed that Ih current is significantly enhanced by Aβ injection, and this effect is further strengthened by treatment with melatonin in Aβ-injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aβ-injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after-hyperpolarization and Ih currents due to Aβ-induced neurotoxicity.

The Biochemical Effects of Hydroalcoholic Extract of Quercus brantii Fruit on Morphine-Induced Amnesia in the Presence and Absence of Cholinergic Muscarinic Receptors in Adult Male Mice

Background: In our previous study, we demonstrated that oak hydroalcoholic extract improves memory impairment in a postpartum depression model due to its antioxidant properties. The purpose of this study is to further investigate the effect of oak on another amnesia model and explore the mediating role of cholinergic muscarinic receptors. Objectives: This study investigated the effect of hydroalcoholic extract of oak fruit on amnesia induced by morphine in the presence and absence of cholinergic muscarinic receptors, as well as changes in serum biochemical factors. Methods: In this experimental study, adult male mice were divided into groups: Control and morphine-receiving (5 and 7.5 mg/kg) groups to induce amnesia after training. In the groups receiving 7.5 mg/kg morphine, oak extract (1 and 10 mg/kg) was administered one day after training and continued for one week. Atropine (0.1 and 1 mg/kg) was injected only on the first day after training and before the oak extract injection. Passive avoidance memory was evaluated 1, 3, and 7 days after training using a step-down device. Motor activity was assessed using the open field test. Blood biochemical factors, including triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total antioxidant capacity (TAC), were measured after one week of injections. Results: Morphine (7.5 mg/kg) impaired memory on days 1 and 7 (P &lt; 0.05), while oak extract (1 and 10 mg/kg) improved memory (P &lt; 0.001). Additionally, the oak extract maintained its enhancing effect even in the presence of atropine, a cholinergic muscarinic system antagonist. Oak extract significantly increased HDL and TAC levels but did not affect LDL, cholesterol, and triglyceride levels. Conclusions: These findings suggest that oak extract can improve morphine-induced amnesia due to its antioxidant effect, without involving the cholinergic system. Additionally, oak extract can increase beneficial lipids without affecting harmful lipids.

Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury.

The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.

Protective effects of L-carnitine against beta-amyloid-induced memory impairment and anxiety-like behavior in a rat model of Alzheimer's disease

Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of β-amyloid1-42 (Aβ1-42). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aβ1-42 resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aβ plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aβ1-42 through modulating oxidative-antioxidant status and preventing Aβ plaque accumulation and neuronal death.

Early-life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions.

Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiologicaland cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early-life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para-chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10-20, followed by sleep deprivation-induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain-derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aβ1-42). Oral administration of SEL at a dose of 0.5mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aβ through modulation of oxidative-antioxidant status.

Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.