Memory Function In Rats Research Articles

Genetic patterning in hippocampus of rat undergoing impaired spatial memory induced by long-term heat stress

The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of Arhgap36 in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of Arhgap36 in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.

Influences of quality of maternal care and environmental enrichment on associative memory function in rats with early life lead exposure.

Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure. Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From postnatal days (PNDs) 2-9, maternal care behaviors were observed, and dams were classified as low or high maternal care based on amounts of licking/grooming and arched back nursing. At weaning, pups were randomly assigned to enriched or non-enriched environments. At PND 55, animals began trace fear conditioning and associative memory was tested on days 1, 2, and 10 postconditioning. Control offspring showed no significant effects of maternal care or enrichment on task performance. Females with EPN-Pb exposure and males with PERI-Pb exposure living in the non-enriched environment and having an LMC mother had significant memory impairments at days 2 and 10 that were not observed in comparably housed animals with HMC mothers. Enriched animals had no deficits, regardless of maternal care status. These results show the potential for modulatory influences of maternal care and housing environment on protecting against or reversing at least one aspect of Pb-induced cognitive/behavioral dysfunction.

Effects of simulated gas of thermobaric bomb charge explosion on Tau protein phosphorylation and cognitive function in rats

Objective: To explore the effect of simulated gas of thermobaric bomb charge explosion on cognitive function and the related mechanism of damage. Methods: In January 2022, thirty-two SPF rats were selected and randomly divided into control group, exposed group 1, 2 and 3 (the exposure time of the simulated gas of the explosion of the thermobaric bomb charge was 5 min, 10 min and 15 min, respectively) according to random number table method, with 8 rats in each group. The simulated gas of the explosion of the thermobaric bomb charge were CO 0.15%, CO(2) 3%, NO 0.1%, O(2) 15%, and the rest were N(2). After 30 days of exposure, water maze was used to detect the learning and memory function of rats. Golgi staining was used to observe the number distribution and morphological structure of hippocampal neurons in rats. Western blot was used to detect the expression of Tau-5, pSer262, pSer396, pThr181 and pThr231 proteins in rats. Repeated measure ANOVA was used to compare the design data of repeated measure, one-way ANOVA was used for multi-group mean comparison, and LSD method was used for pound-wise comparison. Results: There were significant differences in the results of repeated measurement ANOVA of the water maze localization navigation test (F=80.98, P<0.001), and there was an interaction between the group and the training days (F=2.16, P=0.022). There were significant differences in escape latency of rats at the 2nd, 3rd, 4th and 5th days among all groups (P<0.05). The results of spatial exploration showed that the frequency of rats crossing the platform was significantly different among all groups (F=4.49, P=0.011). The frequency of rats crossing the platform in exposed group 2 and exposed group 3 was lower than that in control group, and the frequency of rats crossing the platform in exposed group 3 was lower than that in exposed group 1 (P<0.05). With the increase of exposure time, the number of hippocampal neurons decreased, and the dendrite spine density of neurons in CA1 region decreased (P<0.05). Compared with the control group, there was no significant difference in the relative expression level of Tau-5 protein in all exposed groups (P>0.05), but the expression level of pSer262 protein was significantly increased (P<0.05). Compared with the control group, the protein expressions of pSer396, pThr181 and pThr231 in exposed group 2 and exposed group 3 were significantly increased (P<0.05) . Conclusion: The simulated gas of the explosion of the thermobaric bomb charge may contribute to the development of cognitive dysfunction by damaging hippocampal neurons with aberrant phosphorylation of Tau proteins.

The mechanism of miR-665 targeting GNB3 in aluminum-induced neuronal apoptosis

BackgroundAluminum exerts neurotoxic effects through various mechanisms, mainly manifested as impaired learning and memory function. MethodsForty SD rats were divided into 0, 10, 20, and 40 mM maltol aluminum [Al(mal)3] groups. Cell experiments are divided into 0, 100, 200, and 400 μM Al(mal)3 dose group and control, Al(mal)3, Al(mal)3+inhibitor NC, Al(mal)3+miR-665 inhibitor intervention group. Water maze was used to detect the learning and memory function of rats, HE staining was used to observe the morphology and number of neurons in the CA1 area of the rat hippocampus, Flow cytometry was used to detect the apoptosis of PC12 cells, PCR and Western blotting were used to detect the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins. The target binding relationship between miR-665 and GNB3 was verified by double luciferase reporter gene experiment. ResultsIn vivo experimental results showed that with the increase of Al(mal)3 concentration, the escape latency of rats was prolonged, the target quadrant dwell time was shortened, and the number of crossing platform was reduced. Moreover, the arrangement of neurons was loose and the number decreased; the expression of Caspase3 and miR-665 increased, while the expression of GNB3/PI3K/AKT proteins decreased. In vitro experiments, with the increase of Al(mal)3 concentration, apoptosis rate of PC12 cells increased, the expression of Caspase3, miR-665 and GNB3/PI3K/AKT proteins were consistent with rat results. After inhibiting miR-665 in the intervention group experiment, apoptosis rate of PC12 cells in the aluminum exposure group decreased, the expression of Caspase3 and miR-665 decreased, and the expression of GNB3/PI3K/AKT proteins increased. ConclusionMiR-665 plays an important role in aluminum induced neuronal apoptosis by targeting GNB3 and regulating the PI3K/AKT pathway.

Artesunate improves learning and memory impairment in rats with vascular cognitive impairment by down-regulating the level of autophagy in cerebral cortex neurons

BackgroundVascular cognitive impairment (VCI) is the second leading cause of dementia. Cognitive impairment is a common consequence of VCI. However, there is no effective treatment for VCI and the underlying mechanism of its pathogenesis remains unclear. This study to investigate whether artesunate (ART) can improve the learning and memory function in rats with VCI by down-regulating he level of autophagy in cerebral cortex neurons. MethodsThe models for VCI were the rat bilateral common carotid artery occlusion (BACCO), which were randomized into three groups including the sham operation group (Sham), model + vehicle group (Model) and model + ART group (ART). Then the animal behaviors were recorded, as well as staining the results of cortical neurons. Western blot was performed to determine the protein expressions of LC3BⅡ/Ⅰ, p-AMPK, p-mTOR, and Beclin-1. ResultsBehavioral outcomes and the protein expressions in Model group were supposedly affected by the induction of autophagy in cerebral cortex neurons. Compared to the Model group, ART improved memory impairment in VCI rats. And the expression of LC3BⅡ/Ⅰ, p-AMPK/AMPK, Beclin-1 is significant decreased in the ART group, while significant increases of p-mTOR/mTOR were showed. These results suggest that ART improved learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons. ConclusionThe results suggest that autophagy occurs in cerebral cortex neurons in rats with VCI. It is speculated that ART can improve learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats

ABSTRACT Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer’s (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented β-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms

IntroductionEpilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms.MethodsLithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group.ResultsFirst, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced.Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses.Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2.ConclusionThe current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.

Comparison of the effect of postweaning social isolation, enriched environment, and exercise training on learning and memory functions in rats.

To assess the effects of postweaning social isolation, an enriched environment, and exercise training on learning and memory functions in rats, as well as their relation with the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations in the hippocampus. Randomly assigned into 4 groups were 35 female postweaning rats (25 day old), as the control (C), social isolation (SI), enriched environment (EE), and exercise training (E) groups. The SI and the EE groups were housed under their specific conditions and the E and the C groups were housed under standard conditions for 6 weeks. The rats in the E group swam for 60 min/day, 5 days a week, for 6 weeks. After 6 weeks, the rats were evaluated in the Morris water maze (MWM). Following MWM assessment, hippocampal tissue and blood samples were taken to measure the BDNF and NGF. According to the results of the MWM probe trial session, the thigmotaxis behavior was higher in the SI group compared to the C group (p < 0,05). Furthermore, the time spent in the target quadrant (quadrant with an escape platform) was lower in the SI group compared to the EE group (p < 0.05). The BDNF and NGF levels in the hippocampus and plasma were not different between the groups (p < 0.05). Postweaning social isolation may increase thigmotaxis behaviors. Postweaning social isolation, enriched environment, and exercise training did not affect the spatial learning, memory function, hippocampal BDNF or NGF levels in female rats.

Photobiomodulation Promotes Hippocampal Neurogenesis and Improves Cognitive Function and Anti-Inflammatory Injury in Rats With Chronic Cerebral Hypoperfusion

To investigate the effect of photobiomodulation (PBM) on hippocampal neurogenesis, cognitive function, and inflammatory injury in rats with chronic cerebral hypoperfusion. Bilateral ovariectomy (OVX) was performed on female Sprague-Dawley (SD) rats. One week later, the rats were randomly assigned to three groups, Sham surgery (or Sham) group, bilateral common carotid artery occlusion (BCCAO) group, and PBM intervention (or BCCAO+PBM) group. There were 8 rats in each group. In the BCCAO group, chronic cerebral hyporeperfusion was induced by permanent ligation of bilateral common carotid arteries and no PBM was given. Rats in the Sham group underwent the same surgical procedure except for the occlusion of the two carotids arteries and no PBM was given. In addition to the BCCAO surgery, rats in the BCCAO+PBM group received 808 nm laser therapy (5 min each time at a laser dose of 20 mW/cm 2) of the frontal cortex every other day for 1 month. Between 86 and 90 days after BCCAO, Morris water maze (MWM) was used to observe the spatial learning and memory function of the rats. The rats were sacrificed on day 90 and immunofluorescence staining and Western blot were performed thereafter. Immunofluorescence staining was used to determine the expression of 5-bromodeoxyuracil nucleoside (BrdU), a cell proliferation marker, glial fibrillary acidic protein (GFAP), an astrocyte marker, doublecortin (DCX), a specific marker of newborn neuron precursor cells, NeuN, a marker of mature neurons, and Iba1, a microglia marker, in the hippocampal dentate gyrus (DG) region. Western blot was performed to analyze the protein expressions of inflammasome components, NLRP3, ASC, cleaved caspase-1, and Iba1 in the hippocampus. In the latency trial of MWM test, BCCAO+PBM rats spent shorter periods of time finding the underwater platform than the BCCAO rats did. In the probe trial, after the platform that was original placed in a quadrant was removed, the BCCAO+PBM rats spent longer periods of time exploring the quadrant than the BCCAO animals did ( P<0.05). Compared with BCCAO rats, BCCAO+PBM rats showed significant decrease in the immunofluorescence intensities of GFAP and Iba1 ( P<0.01). PBM intervention significantly increased the number of BrdU-positive cells in the hippocampal DG region compared with those of Sham and BCCAO groups ( P<0.05). Furthermore, the number of NeuN positive cells showed no significant difference among the three groups, while in BCCAO+PBM group, the number of DCX-positive cells was significantly increased ( P<0.001) and the number of DCX +/NeuN + co-located cells was significantly increased compared to that of the BCCAO group ( P<0.001). Compared with those of the BCCAO group, Western blot results showed that the protein expression levels of Iba1, NLRP3, and cleaved caspase-1 in the BCCAO+PBM group were significantly decreased ( P<0.05), while the ASC protein expression level showed no significant difference. PBM can effectively improve the spatial learning and memory function in rats with chronic cerebral hypoperfusion, inhibit the activation of glial cells, reduce inflammatory damage mediated by NLRP3 inflammasome, and promote the regeneration of endogenous neural stem cells in the hippocampal DG region of rats.

New findings about comparing the effects of antibiotic therapy and phage therapy on memory and hippocampal pyramidal cells in rats.

Pseudomonas aeruginosa is a significant cause of infection in burn wounds. Antibiotics are widely used to treat infectious diseases, and alongside their therapeutic benefits, they can damage host cells. Significant side effects, such as nephrotoxicity and neurotoxicity, are observed in 60% of patients treated with colistin. Therefore, using a suitable alternative instead of antibiotics is paramount. This study aimed to investigate the effects of phage therapy and antibiotic therapy on memory function in rats with P. aeruginosa infected burn wounds. Adult male rats were divided into three groups: (1) infected without treatment (control), (2) infected and treated with colistin antibiotic (3,000,000 international units/kg/day), and (3) infected and treated with 100 μL of phage suspension (approximately 109 PFU/mL). In all animals, after anesthesia, a third-degree burn was created in the back area. One hour later, treatment was performed for seven consecutive days. Passive avoidance test, novel object recognition test, locomotion activity, hippocampal neuron count, and oxidative stress measurement in blood serum were performed. In antibiotic-treated group memory recall, recognition index, number of healthy neurons in CA1, CA2, and CA3 hippocampus areas and the amounts of MDA, and FRAP significantly decreased compared with the control group. The phage-treated group was not shown any harmful effect on the memory process, number of healthy hippocampal neurons, and showed more positive effects in blood serum examinations compared with the antibiotic group. Phage therapy could be a safe and effective alternative to antibiotics in the treatment of burn-related infections.

Chrysophanol exerts a protective effect against Aβ25-35-induced Alzheimer's disease model through regulating the ROS/TXNIP/NLRP3 pathway.

The primary pathogenic factors of Alzheimer's disease (AD) have been identified as oxidative stress, inflammatory damage, and apoptosis. Chrysophanol (CHR) has a good neuroprotective effect on AD, however, the potential mechanism of CHR remains unclear. In this study, we focused on the ROS/TXNIP/NLRP3 pathway to determine whether CHR regulates oxidative stress and neuroinflammation. D-galactose and Aβ25-35 combination were used to build an in vivo model of AD, and the Y-maze test was used to evaluate the learning and memory function of rats. Morphological changes of neurons in the rat hippocampus were observed using hematoxylin and eosin (HE) staining. AD cell model was established by Aβ25-35 in PC12 cells. The DCFH-DA test identified reactive oxygen species (ROS). The apoptosis rate was determined using Hoechst33258 and flow cytometry. In addition, the levels of MDA, LDH, T-SOD, CAT, and GSH in serum, cell, and cell culture supernatant were detected by colorimetric method. The protein and mRNA expressions of the targets were detected by Western blot and RT-PCR. Finally, molecular docking was used to further verify the in vivo and in vitro experimental results. CHR could significantly improve learning and memory impairment, reduce hippocampal neuron damage, and reduce ROS production and apoptosis in AD rats. CHR could improve the survival rate, and reduce the oxidative stress and apoptosis in the AD cell model. Moreover, CHR significantly decreased the levels of MDA and LDH, and increased the activities of T-SOD, CAT, and GSH in the AD model. Mechanically, CHR significantly reduced the protein and mRNA expression of TXNIP, NLRP3, Caspase-1, IL-1β, and IL-18, and increase TRX. CHR exerts neuroprotective effects on the Aβ25-35-induced AD model mainly by reducing oxidative stress and neuroinflammation, and the mechanism may be related to ROS/TXNIP/NLRP3 signaling pathway.

Modulatory Role of Curcumin on Cobalt-Induced Memory Deficit, Hippocampal Oxidative Damage, Astrocytosis, and Nrf2 Expression.

Chemical overexposure is a growing environmental risk factor for many medical issues. Cobalt toxicity from environmental, industrial, and medical exposure has previously been linked to neurological impairment. Hence, the current study looked into the neuroprotective potential of curcumin, a natural polyphenol contained in the spice turmeric, against cobalt-induced neurotoxicity. Adult rats were randomly divided into six groups as follows: control, 40mg/kg cobalt chloride (CoCl2) only, 240mg/kg curcumin only, 120mg/kg or 240mg/kg curcumin, or 100mg/kg vitamin C co-administered with CoCl2. The administration was via oral route daily for 4weeks. After that, neurobehavioral tests were undertaken to evaluate short-term spatial memory. Biochemical investigation was performed to determine the hippocampal levels of status via measures of SOD, CAT, GST, and LPO. Furthermore, immunohistochemical assessment of the expression of GFAP and Nrf2 in the hippocampus was carried out. In the CoCl2 group, the results showed altered behavioral responses, a decrease in antioxidant activities, increased expression of GFAP and the number of activated astrocytes, and decreased immunoexpression of Nrf2. These effects were mitigated in the curcumin- and vitamin C-treated groups. These results collectively imply that curcumin enhances memory functions in rats exposed to cobalt possibly by attenuating oxidative responses, mitigating astrocytosis, and modulating Nrf2 signaling.

Electroacupuncture improves cognitive impairment in diabetic cognitive dysfunction rats by regulating the mitochondrial autophagy pathway

BackgroundDiabetes-associated cognitive dysfunction has become a major public health concern. However, the mechanisms driving this disease are elusive. Herein, we explored how electroacupuncture improves learning and memory function in diabetic rats.MethodsThe diabetic model was established by intraperitoneal injection of streptozotocin (STZ) in adult Sprague–Dawley rats. Rats were fed on high-fat and high-sugar diets. Learning and memory functions were assessed using behavioral tests. The hematoxylin and eosin (H&E) staining, Western blotting, real-time PCR, ELISA, immunohistochemistry, and transmission electronic microscopy (TEM) was performed to test related indicators.ResultsHigh-fat and high-sugar diets impaired learning and memory function in rats, while electroacupuncture treatment reversed these changes. The model group presented highly prolonged escape latency compared to the control group, indicating impaired learning and memory functions. The TEM examination showed that electroacupuncture enhanced Aβ clearance and mitochondrial autophagy in hippocampal neuronal cells by increasing DISC1 expression.ConclusionsElectroacupuncture improves learning and memory function in diabetic rats by increasing DISC1 expression to promote mitophagy. This enhanced Aβ clearance, alleviating cytotoxicity in hippocampal neuronal cells.

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats.

Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region-specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.

Silver nanoparticles synthesized using Tualang honey ameliorate seizures, locomotor activity, and memory function in KA-induced status epilepticus in male rats

Introduction: In recent years, green synthesis of silver nanoparticles using natural products has been increasingly utilized in the biomedical field as a therapeutic approach for managing neurodegenerative diseases. This study aimed to determine the effects of silver nanoparticles synthesized using Tualang honey (THSN) on seizure activity and locomotor and memory functions in rats after kainic acid (KA) induction. Methods: Male Sprague Dawley rats were randomly divided into six groups (n = 6/group), and each group was pre-treated orally with either distilled water or THSN (10 mg/kg or 50 mg/kg), according to their respective groups. Each rat was injected subcutaneously with KA (15 mg/kg) or saline after the last pre-treatment, and the onset of the first generalized seizure was recorded. After 24 hours and five days of KA induction, an open field test (OFT) and a novel object recognition test (NORT) were performed before they were sacrificed. Results: THSN pre-treatment of KA-induced status epilepticus groups demonstrated an increment in latencies to the onset of the first generalized seizure and the number of line crossings in OFT, with a higher recognition index of NORT compared to the untreated KA-induced status epilepticus group. Conclusion: THSN could have neuroprotective effects in ameliorating seizures, locomotor activity, and memory function after KA-induced status epilepticus in male rats.

Mechanism of Dexmedetomidine Intervention on Neurogenic Inflammation in Cognitive Impairment Rats after Partial Hepatectomy.

Objective To study the effect of dexmedetomidine on cognitive function in rats with cognitive impairment after partial hepatectomy and its mechanism. Methods 60 SD rats were randomly divided into 4 groups (n = 15): blank control group (CG group), sham operation group (Sham group), cognitive impairment model group (POCD group), and dexmedetomidine + cognitive impairment model group (DEX group). Rats in the POCD group underwent left lobe hepatectomy and intraperitoneal injection of the same amount of normal saline after resuscitation. Rats in the DEX group underwent left lobe hepatectomy and intraperitoneal injection of dexmedetomidine 50 μg/kg. Group CG was not operated on and the same amount of normal saline was injected intraperitoneally. In the Sham group, liver resection was not allowed after the abdominal incision, and normal saline was injected intraperitoneally. Rats were injected every 24 hours for 5 consecutive days. Morris water maze (MWM) were used to evaluate the effects of dexmedetomidine on learning and memory ability of POCD rats. TUNEL method was used to detect apoptotic neurons in the hippocampus. INOS, Arg-1, IL-6, and TNF-αexpression levels were detected. Western blot detects the expression level of TNF-α, Bcl-2, and NF-κB protein. Result Compared with the CG group, the escape latency of the other three groups was prolonged on the 5th day after the operation, and the number of crossing the platform was reduced. Compared with the Sham group, the escape latency of the POCD group and DEX group was significantly prolonged, and the number of crossing the platform was significantly reduced on day 5 (P < 0.05). Compared with the POCD group, the DEX group shortened the escape latency and increased the number of crossing the platform on the 5th day (P < 0.05). It shows that the spatial learning and memory function of rats has been restored to a certain extent.The number of iNOS and Arg-1 positive cells in the POCD group and DEX group was higher than that in the control group, and the number of Arg-1 positive cells in the DEX group was higher than that in the POCD group (P < 0.05). Western blot results the expression of Bcl-2 and NF-κB protein in POCD group, and DEX group was higher than that of the sham group (P < 0.05). The expression of Bcl-2 and NF-κB protein was the most in POCD group. The expression of Bcl-2 and NF-κB protein in DEX group was lower than that in POCD group (P < 0.05). Conclusion Behavioral results showed that the learning and cognitive ability of POCD model rats after hepatectomy was impaired, and inflammatory factors and activated microglia were found in the hippocampus of POCD rats. Dexmedetomidine may improve the brain function of POCD rats by inhibiting neuronal apoptosis,partly through NF-κB apoptosis pathway.

JAK2/STAT3 Signaling Pathway and Klotho Gene in Cadmium-induced Neurotoxicity In Vitro and In Vivo.

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction.

Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways

Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system.

Effects of Cathepsin K on spatial learning and memory in rats

To investigate the effects of Cathepsin K(CatK) on spatial learning and memory in rat hippocampus and its mechanisms. Twenty male SD rats were randomly divided into Control group and CatK inhibitor group(CatKⅡ group), which were microinjected with Cathepsin K specific inhibitor(0.5 μg/μl) and artificial cerebrospinal fluid in hippocampal DG area respectively with 5 days. The cultured hippocampal neuron cells were divided into control group (CON group), negative control group(NC group), siRNA interference group(siCatK group). Three re-wells were set for each group, and samples were collected 18～20 h after siRNA transfection. Morris water maze was used to evaluate spatial learning and memory function of rats. Meanwhile, dynamic changes of glutamate(Glu) content in extracellular fluid of DG region during learning and memory were observed by microdialysis and high performance liquid chromatography in conscious rats. Western blot was used to detect CatK-mediated Notch1 activation and other signal molecules. Animal experiments showed that compared with the control group, the spatial learning and memory ability were decreased significantly in CatKII group, and the hippocampus protein expressions of c-Notch1, p-Akt, p-CREB and BDNF were also decreased significantly(P＜0.05); the levels of Glu in DG area of control group and CatK II group were increased significantly with Morris water maze training days, but the increase of CatK II group was significantly weaker than that of control group(P＜ 0.05). The results of cell experiment showed that the expressions of CatK, c-Notch1, p-CREB and BDNF in siCatK group were significantly lower than other groups (P＜0.05). CatK can affect the spatial learning and memory function of rats by activating Notch1 and its memory related signal protein in hippocampus.

Sevoflurane exposure during the second trimester induces neurotoxicity in offspring rats by hyperactivation of PARP-1.

Fetal exposure to general anesthesia may cause noteworthy neurocognitive impairment, but the mechanisms are unclear. Our study designed to explore the potential mechanism of neurotoxicity in offspring rats after sevoflurane exposure to the pregnant rats during the second trimester. Pregnant rats (G14 day) were administrated with or without 3.5% sevoflurane, 40mg/kg 3-aminobenzamide (3-AB), inhibitor of poly ADP ribose polymerase 1 (PARP-1), or 10mg/kg TC-2153, inhibitor of striatal-enriched phosphatase 61 (STEP61). Afterwards, the effects on expression of β-tubulin (TUJ1), neurite outgrowth inhibitor A (Nogo-A), parthanatos-related and STEP61/proline-rich tyrosine kinase 2 (Pyk2) pathway-associated proteins, and reactive oxygen species (ROS) levels were examined by immunofluorescence staining, Western blot, and dihydroethidium (DHE) staining, respectively. Moreover, morphological changes in the hippocampal CA3 region and neuronal cell death were tested by glycine silver staining and TUNEL and immunofluorescence double staining, respectively. Furthermore, spatial learning and memory functions of rats on postnatal 28-33days (PND 28-33) were evaluated by morris water maze (MWM). Mid-pregnancy exposure to sevoflurane led to excessive PARP-1 activation, poly (ADP-ribose) (PAR) polymer accumulation, apoptosis-inducing factor (AIF) nuclear translocation, and Nogo-A accumulation. Besides, sevoflurane significantly inhibited neurite growth and increased cell death in the fetal rat brain. Additionally, sevoflurane activated STEP61/Pyk2 pathway and increased ROS levels. However, 3-AB or TC-2153 significantly alleviated cell death, promoted neurites growth, and improved sevoflurane-induced spatial learning and memory impairment. This study proposes that sevoflurane exposure during the second trimester incudes neurotoxicity in offspring rats by hyperactivation of PARP-1 via STEP61/Pyk2 pathway.