Step-through Passive Avoidance Test Research Articles

Tooth loss in young mice is associated with cognitive decline and femur-bone mineral density.

Osteoporosis is a prevalent disease that is associated with increased hip fractures which cause significant decline in quality of life. Tooth loss affects systemic condition such as cognitive function through various mechanism, but the link between tooth loss and femoral bone mineral density is still uncertain. This study aims to investigate whether tooth loss in young mice affects memory function and femoral bone mineral density. Eight-week-old male C57BL/6J mice were allocated randomly into the control group with sham operation and the tooth-loss group extracted all maxillary molar. Step-through passive avoidance test as cognitive function test, micro-CT analysis and western blotting analysis were performed after 1- and 2-month observation period. Step-through passive avoidance test revealed that the tooth-loss group in 2-month observation period impaired cognitive function. Additionally, micro-CT analysis revealed a significant decrease in both the length of the mandible and bone mineral density in the femur of the tooth-loss group compared to the control group. Claudin-5 level in the hippocampus, which is one of the tight junction markers in blood-brain-barrier, was significantly decreased in the tooth-loss group. The findings of our present study suggested that tooth loss impair cognitive function accompanied by reduced tight-junction marker, mandibular growth and bone mineral density of femur.

Corilagin improves cognitive impairment in APP/PS1 mice by reducing Aβ generation and enhancing synaptic plasticity

Alzheimer's disease (AD) is closely associated with the neurotoxic effects of amyloid-β (Aβ), leading to synaptic damage, neuronal loss and cognitive dysfunction. Previous in vitro studies have demonstrated the potential of corilagin to counteract Aβ-induced oxidative stress, inflammatory injury, and β-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity in Aβ production. However, the in vivo protective effects of corilagin on Alzheimer's disease remain unexplored. The purpose of this study was to investigate the protective effects of corilagin on APP/PS1 mice and the underlying mechanisms. The cognitive function of the mice was assessed by step-through passive avoidance and Morris water maze tests. Nissl staining was used to evaluate neuronal damage in the hippocampus. ELISA and Western blotting analyses were used to determine the associated protein expression. Transmission electron microscopy was utilized to observe the synaptic ultrastructure of hippocampal neurons. Golgi staining was applied to assess dendritic morphology and dendritic spine density in hippocampal pyramidal neurons. Immunohistochemistry and Western blotting were performed to examine the expression of synaptic-associated proteins. The results showed that corilagin improves learning and memory in APP/PS1 mice, reduces hippocampal neuron damage, inhibits BACE1 and reduces Aβ generation. It also improves synaptic plasticity and the expression of synaptic-associated proteins. Corilagin effectively reduces Aβ generation by inhibiting BACE1, ultimately reducing neuronal loss and enhancing synaptic plasticity to improve synaptic transmission. This study sheds light on the potential therapeutic role of corilagin in Alzheimer's disease.

Co-administration of sub-effective doses of the constituents of Crocus sativus L. crocins with those of the antipsychotics clozapine and risperidone counteract memory deficits caused by blockade of the NMDA receptor in rats.

Experimental evidence indicates that the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists ketamine and MK-801 induce schizophrenia-like symptoms in rodents, including cognitive deficits. Crocins are among the active components of the plant Crocus sativus L. and were found to be effective in different models of psychiatric disorders comprising schizophrenia. The present study was designed to evaluate the efficacy of the joint administration of sub-effective doses of crocins with those of the atypical antipsychotics clozapine and risperidone in alleviating nonspatial recognition and emotional memory deficits induced either by ketamine (3 mg/kg) or MK-801 (0.1 mg/kg) in the rat. To this end, the object recognition and the step-through passive avoidance tests were used. Co-administration of sub-effective doses of crocins (5 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) counteracted nonspatial recognition and emotional memory deficits induced by NMDA receptor antagonists. The current findings suggest that this combinatorial treatment was efficacious in attenuating cognitive impairments related to the blockade of the NMDA receptor. In addition, the present results support the potential of crocins as an adjunctive drug for the therapy of schizophrenia.

Effect of woohwangchungsimwon and donepezil co-treatment on cognitive function and serum metabolic profiles in a scopolamine-induced model of Alzheimer's disease

Ethnopharmacological relevanceWoohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). Aim of the studyThe study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. Materials and methodsCell viability and reactive oxygen species (ROS) levels were measured in amyloid β-peptide25–35 (Aβ25–35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy. ResultsCo-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aβ25–35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment. ConclusionsCo-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.

Mouse maternal odontogenic infection with Porphyromonas gingivalis induces cognitive decline in offspring.

Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, causes intrauterine infection/inflammation. Offspring exposed to intrauterine infection/inflammation have an increased risk of neurological disorders, regardless of gestational age. However, the relationship between maternal periodontitis and offspring functional/histological changes in the brain has not yet been elucidated. In this study, we used a gestational mouse model to investigate the effects of maternal odontogenic infection of P. gingivalis on offspring behavior and brain tissue. The step-through passive avoidance test showed that the latency of the acquisition trial was significantly shorter in the P. gingivalis group (p < 0.05), but no difference in spontaneous motor/exploratory parameters by open-field test. P. gingivalis was diffusely distributed throughout the brain, especially in the hippocampus. In the hippocampus and amygdala, the numbers of neuron cells and cyclic adenosine monophosphate response element binding protein-positive cells were significantly reduced (p < 0.05), whereas the number of ionized calcium binding adapter protein 1-positive microglia was significantly increased (p < 0.05). In the hippocampus, the number of glial fibrillary acidic protein-positive astrocytes was also significantly increased (p < 0.05). The offspring of P. gingivalis-infected mothers have reduced cognitive function. Neurodegeneration/neuroinflammation in the hippocampus and amygdala may be caused by P. gingivalis infection, which is maternally transmitted. The importance of eliminating maternal P. gingivalis-odontogenic infection before or during gestation in maintenance healthy brain function in offspring should be addressed in near future.

Effects of 3R, 16S-2-hydroxyethyl apovincaminate (HEAPO), donepezil and galantamine on learning and memory retention in naïve Wistar rats.

The effects of 3R,16S-2-hydroxyethyl apovincaminate (HEAPO, RGH-10885) compared with those of two cholinesterase inhibitors, donepezil and galantamine, were examined in naïve Wistar rats using standard active and passive avoidance tests. The active avoidance test (shuttle box) and two passive avoidance tests (step-through and step-down) were performed according to the experimental design. There were 10 groups of rats (n = 8) and the substances studied were applied orally before each testing session. In the active avoidance test, the number of conditioned stimuli (avoidances), unconditioned stimuli (escapes) and intertrial crossings were observed. In step-down and step-through passive avoidance tests, the latencies of reactions were observed. All the studied compounds showed positive effects in the learning and memory tests, compared to the controls. It was concluded that HEAPO, donepezil and galantamine had a memory-enhancing effect in active and passive avoidance tests.

Exercise by Shaking Alleviates the Decline in Memory due to Aging: A Study in Mice

Introduction: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking. This study examined the possibility to prevent the decline in memory through regular and long-term shaking exercise using a senescence-accelerated mouse (SAM) model. Behavioral analysis was conducted, and histological changes in the mouse brain were examined to evaluate whether this stimulation method could become a novel exercise method. Materials and Methods: The shaking exercise was applied to SAMP10 mice for 30 min 3 times per week for 25 continuous weeks. Behavioral analysis included a step-through passive avoidance test, whereas the histological analysis involved immunohistochemical staining using the anti-glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors [AMPAR]) antibody in the hippocampus. The number and area of nerve cells in the hippocampal regions were measured and compared between groups. Results: Behavioral analysis revealed that the shaking group retained memory longer than the control group, and memory capacity decline was suppressed. Additionally, histological examination showed that the shaking group had a higher number of AMPAR receptor-positive neurons per area in the hippocampal CA1 and CA3 regions than the control group, suggesting that degeneration and shedding of neurons due to aging was suppressed. Discussion/Conclusion: We believe that shaking could become an exercise therapy that can reduce the decline in memory with aging and expect its human application in the future.

A Comparative Study of Two Models of Intraluminal Filament Middle Cerebral Artery Occlusion in Rats: Long-Lasting Accumulation of Corticosterone and Interleukins in the Hippocampus and Frontal Cortex in Koizumi Model.

Recently, we have shown the differences in the early response of corticosterone and inflammatory cytokines in the hippocampus and frontal cortex (FC) of rats with middle cerebral artery occlusion (MCAO), according to the methods of Longa et al. (LM) and Koizumi et al. (KM) which were used as alternatives in preclinical studies to induce stroke in rodents. In the present study, corticosterone and proinflammatory cytokines were assessed 3 months after MCAO. The most relevant changes detected during the first days after MCAO became even more obvious after 3 months. In particular, the MCAO-KM (but not the MCAO-LM) group showed significant accumulation of corticosterone and IL1β in both the ipsilateral and contralateral hippocampus and FC. An accumulation of TNFα was detected in the ipsilateral hippocampus and FC in the MCAO-KM group. Thus, unlike the MCAO-LM, the MCAO-KM may predispose the hippocampus and FC of rats to long-lasting bilateral corticosterone-dependent distant neuroinflammatory damage. Unexpectedly, only the MCAO-LM rats demonstrated some memory deficit in a one-trial step-through passive avoidance test. The differences between the two MCAO models, particularly associated with the long-lasting increase in glucocorticoid and proinflammatory cytokine accumulation in the limbic structures in the MCAO-KM, should be considered in the planning of preclinical experiments, and the interpretation and translation of received results.

Anti-Alzheimer’s Activity of Methanolic Tender Green Pod Extract of Cyamopsis Tetragonoloba (L.) Taub. on Scopolamine Induced Amnesia in Mice

Background: Alzheimer’s disease (AD) is a chronic and prevalent neurodegenerative disease that leads to memory loss, especially in the elderly. AD is caused by a lack of acetylcholine in the brain and oxidative stress. The Cyamopsis tetragonoloba, also known as Guar or cluster bean, is a legume that belongs to the family Fabaceae. It is cheap, widely consumed as a seasoned vegetable, and reported to counteract chronic diseases linked to oxidative stress, such as diabetes, dyslipidemia, inflammation, and ulcer. Objective: The present study was undertaken to assess the anti-alzheimer’s activity of a tender green pod extract of Cyamopsis tetragonoloba on learning and memory impairment induced by scopolamine. Methods: The extract's total phenolic and flavonoid content was determined using a UV-visible spectrophotometer. The Cyamopsis tetragonoloba methanolic pod extract (CTMPE) at a dose of 100 and 200 mg/kg and donepezil 2.5 mg/kg was administered orally for 7 successive days. On the seventh day, a single intraperitoneal injection of scopolamine was used to induce dementia. The behavioral experiments included an elevated plus maze, step-through passive avoidance, radial arm maze, and Y-maze tests were conducted. The mice were sacrificed and acetylcholine, acetylcholinesterase, and oxidative stress markers were measured in brain homogenate. Results: The total phenolic and flavonoid content was found as 12.9 mg of GAE/g and 1.71 mg of QE/g, respectively. Scopolamine caused memory deterioration, as well as changes in acetylcholine, acetylcholinesterase, and increased oxidative stress in the brain. Mice pretreatment with CTMPE at both doses attenuated scopolamine-induced behavioral, neurochemical, and oxidative changes in a similar way to donepezil. Conclusion: The CTMPE showed an anti-amnesic effect that makes it a promising candidate targeting multiple events as a potential strategy to curb the progression of cognitive impairment.

Tenuifolin ameliorates chronic restraint stress-induced cognitive impairment in C57BL/6J mice.

The general consensus is that stress affects the central nervous system and can lead to cognitive problems. The root of Polygala tenuifolia (P. tenuifolia) is a well-known traditional Chinese medicine used for improving brain function. Tenuifolin (TEN) is the major constituent of P. tenuifolia and has a promising neuroprotective property. The purpose of this study was to investigate the alleviating effect of TEN on cognitive impairment induced by chronic restraint stress (CRS) and its mechanism. Our results showed that CRS exposure resulted in impaired cognitive performance in C57BL/6J mice, as indicated by decreased responses in Y-maze, novel objects recognition, and step-through passive avoidance tests. TEN treated daily orally (10 and 20 mg/kg) for 30 days reversed these behavior changes. Meanwhile, TEN could significantly regulate interleukin (IL)-6 and IL-10 levels in the hippocampus. TEN inhibited the toll-like receptor 4/nuclear factor-kappa B-mediated inflammation, as well as adrenocorticotropic hormone and corticosterone levels in serum. Most importantly, we found that TEN also upregulated the expressions of brain-derived neurotrophic factor, tropomyosin kinase B, glucocorticoid receptor, glutamate receptor 1, and synapse-associated proteins. Collectively, these data suggest that TEN has a potential improvement effect on memory loss caused by CRS.

Chronic exposure to metam sodium causes cognitive impairment in adult mice: evidence of hippocampal neuroinflammation

Neuroinflammation is a significant pathological feature contributing to cognitive deficits that can arise from exposure to environmental toxicants such as pesticides. Metam sodium (MS) is one of the emergent pesticides largely used in the agriculture and public health sectors. In the present study, we verified whether exposure to this compound would affect cognitive performance, and induce neuroinflammation as an underlying mechanism. In this context, mice received chronic treatment with different doses of MS and were submitted to novel object recognition and step-through passive avoidance tests. Hippocampal regions from treated animals underwent an immunohistochemical evaluation of the expression of GFAP and Iba-1 as markers of astrocytes and microglia respectively. The main findings showed that chronic exposure to MS resulted in a decrease in the ratio of time spent beside the novel object and strep-through latency indicating alterations in recognition memory as well as short- and long-term memory respectively. Moreover, treated animals exhibited a significant rise in immunostaining of neuroinflammatory markers GFAP and Iba-1 in the dentate gyrus as well as in the CA1 and CA3 areas of the hippocampus. The present work demonstrates that MS diminished cognitive performance in tasks relying on hippocampal-dependent memory closely associated with high expression of neuroinflammatory markers.&#x0D; Keywords: Metam sodium; cognitive performance; neuroinflammation; hippocampus; GFAP; Iba-1.

The bidirectional effect of prelimbic 5-hydroxytryptamine type-4 (5-HT4) receptors on ACPA-mediated aversive memory impairment in adult male Sprague-Dawley rats.

Objective(s):This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. Materials and Methods: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 μl/rat into the PL area (0.3 μl per side).Results:The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 μg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 μg/rat with ineffective (0.001 μg/rat) or effective (0.1 μg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 μg/rat); but its concomitant use with an effective dose of ACPA (0.1 μg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity.Conclusion:This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors.

P53 and clock genes play an important role in memory and learning ability depression due to long-term ultraviolet A eye irradiation.

Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear. In this study, ICR mice were used to study the effects of long-term UVA eye irradiation. The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD+), and sirtuin 1 (Sirt1) in the brains of treated and control animals. The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD+, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability. These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD+ constructional system, resulting in reduced memory and learning ability.

Ginsenoside Re protects against chronic restraint stress-induced cognitive deficits through regulation of NLRP3 and Nrf2 pathways in mice.

Exposure to chronic stress negatively affects the development of cognition, characterized by learning and memory decline. Ginsenoside Re (GRe), an active compound derived from Panax ginseng, exhibited neuroprotective activity in various neurological diseases. In this study, the protective effect of GRe on chronic restraint stress (CRS)-induced memory deficit was investigated. The mice were experienced 35 days of the CRS induction. The GRe was administered daily orally (10, 20, or 40 mg/kg) during the next 3 weeks stress session and the behavior test period. The CRS-induced memory impairment mice were subjected to behavioral tasks, such as the Y-maze, novel objects recognition, and step-through passive avoidance tests. Nissl staining was used to examine the neuron numbers. The levels of antioxidant enzymes, malondialdehyde, and proinflammatory factor were determined by kits and ELISA assays. The expressions of brain-derived neurotrophic factor (BDNF), NOD-like receptor protein 3 (NLRP3), nuclear factor erythroid-2 related factor 2 (Nrf2) and synapse-associated proteins (synaptophysin, SYP, and postsynaptic density 95, PSD95) were measured by Western blotting. Behavioral assessments indicated that GRe could ameliorate the cognitive impairment of CRS-induced mice, as indicated by increased responses in Y-maze (p < .05), novel objects recognition (p < .01), and step-through passive avoidance tests (p < .01). In addition, GRe treatment significantly decreased the neuronal loss in CRS mice in histological examination. Moreover, chronic GRe treatment significantly ameliorated the down-regulated the expressions of BDNF, Nrf2, heme oxygenase (HO)-1, SYP, and PSD95, as well as up-regulated NLRP3, the adaptor protein ASC, and Caspase-1 protein expression in the hippocampus of CRS-treated mice. Taken together, these findings suggest that GRe has a potential therapeutic effect on memory impairment in C57BL/6J mice exposed to CRS paradigm.

Exercise and pharmacological inhibition of histone deacetylase improves cognitive function accompanied by an increase of gene expressions crucial for neuronal plasticity in the hippocampus

Exercise is recognized to increase the expression of neurotrophic genes in the hippocampus and prevent cognitive impairment. Histone deacetylase (HDAC) inhibitor acetylate histones and enhance gene transcription in epigenetic regulation. HDAC inhibitors are expected to be an efficacious pharmacological treatment for cognitive function. This study aimed to examine the effect of HDAC inhibitors and exercise on epigenetic markers and neurotrophic gene expression in the hippocampus to find a more enriched brain conditioning for cognitive function based on the synergic effects of pharmacological treatment and behavioral therapy.Thirteen-week-old male mice were divided into four groups. Intraperitoneal administration of an HDAC inhibitor (1.2 g/kg sodium butyrate, NaB) and treadmill exercise (approximately 10 m/min for 60 min) were performed 5 days a week for 4 weeks.NaB administration increased the expression of an immediate-early gene, a neurotrophin, and a neurotrophin receptor in the hippocampus. These results indicate that HDAC inhibition could present an enriched platform for neuronal plasticity in the hippocampus and cognitive function. The novel object recognition test showed that NaB administration increased the score. Notably, the step-through passive avoidance test showed improved learning and memory in the presence of exercise and exercise, indicating that the mice acquired fear memory, specifically in the presence of NaB administration plus exercise.This study found that repetitive administration of HDAC inhibitors improved cognitive function and HDAC inhibitor administration plus exercise has a synergic effect on learning and memory, accompanying the enhancement of crucial gene transcriptions for neuronal plasticity in the hippocampus.

Environmental enrichment combined with fasudil treatment inhibits neuronal death in the hippocampal CA1 region and ameliorates memory deficits.

Currently, no specific treatment exists to promote recovery from cognitive impairment after a stroke. Dysfunction of the actin cytoskeleton correlates well with poststroke cognitive declines, and its reorganization requires proper regulation of Rho-associated kinase (ROCK) proteins. Fasudil downregulates ROCK activation and protects neurons against cytoskeleton collapse in the acute phase after stroke. An enriched environment can reduce poststroke cognitive impairment. However, the efficacy of environmental enrichment combined with fasudil treatment remains poorly understood. A photothrombotic stroke model was established in 6-week-old male C57BL/6 mice. Twenty-four hours after modeling, these animals were intraperitoneally administered fasudil (10 mg/kg) once daily for 14 successive days and/or provided with environmental enrichment for 21 successive days. After exposure to environmental enrichment combined with fasudil treatment, the number of neurons in the hippocampal CA1 region increased significantly, the expression and proportion of p-cofilin in the hippocampus decreased, and the distribution of F-actin in the hippocampal CA1 region increased significantly. Furthermore, the performance of mouse stroke models in the tail suspension test and step-through passive avoidance test improved significantly. These findings suggest that environmental enrichment combined with fasudil treatment can ameliorate memory dysfunction through inhibition of the hippocampal ROCK/cofilin pathway, alteration of the dynamic distribution of F-actin, and inhibition of neuronal death in the hippocampal CA1 region. The efficacy of environmental enrichment combined with fasudil treatment was superior to that of fasudil treatment alone. This study was approved by the Animal Ethics Committee of Fudan University of China (approval No. 2019-Huashan Hospital JS-139) on February 20, 2019.

Efficacy of long term administration of curcuma longa linn. on learning and retention memory in albino mice

There is an increase in non-degenerative memory-related disorders in elderly people. Curcuma Longa linn. can induce cognitive improvement by reducing oxidative stress and antioxidant property. This study evaluated the effect of chronic administration of Curcuma Longa linn. on learning and memory in mice. Twenty four male swiss albino mice aged 6 to 8 weeks, weighing 25-30 g were randomized into control, standard, and test groups. Control group received 0.5% Carboxymethylcellulose; the standard group received piracetam and test group received Curcuma Longa linn. orally for 42 days (6 weeks). Water maze test and step-through passive avoidance test were used to evaluate the effect of Curcuma Longa linn. on learning and memory. 1 week of water maze training done (day 40 to 46). On day 47, spatial memory assessment was done. On day 49 retention memory assessment was done. In control, tandard, and test groups, the mean escape latency (EL) was observed to be 42.7, 30.7, and 31.3 seconds on day 43 which decreased to 11.3, 11.6, and 9.8 seconds on 46th day, respectively. The EL in all the three groups decreased from day 43 to Day 46 (p&lt;0.01). The time spent in the northeast target quadrant was more in the test group (21.6 seconds) compared to control (19.9 seconds) and standard group (19.6 seconds) (p=0.768). Test group showed a trend towards improvement in retention memory (p=0.293) in passive avoidance test. In conclusion, Curcuma Longa linn. demonstrated that long term administration may be useful in enhancing the learning in albino mice but there was no improvement in retention of memory in test group mice as compared to the standard and controlled animals.

The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts cognitive deficits induced by the D1/D2 dopaminergic receptor agonist apomorphine in rats.

Schizophrenia is a devastating mental disease that affects nearly 1% of the population worldwide. It is well documented that the dopaminergic (DAergic) system is compromised in schizophrenia. It is of note that the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induces schizophrenia-like symptoms in rodents, including disruption of memory abilities. Neuroactive steroids, comprising dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS), were shown to affect brain DAergic system and to be involved in schizophrenia. BNN27 is a novel DHEA derivative, which is devoid of steroidogenic activity. It has recently been reported that BNN27 counteracted schizophrenia-like behavioural deficits produced by glutamate hypofunction in rats. The aim of the present study was to investigate the ability of BNN27 to attenuate non-spatial, spatial recognition and discrete memory deficits induced by apomorphine in rats. To this end, the object recognition task (ORT), the object location task (OLT) and the step-through passive avoidance test (STPAT) were used. BNN27 (3 and 6mg/kg, i.p.) attenuated apomorphine (0.5mg/kg, i.p.)-induced non-spatial, spatial recognition and discrete memory deficits. Interestingly, the effects of compounds on memory cannot be ascribed to changes in locomotor activity. Our findings suggest that BNN27 is effective to DA dysfunction caused by apomorphine, attenuating cognitive impairments induced by this D1/D2 receptor agonist in rats. Additionally, our findings illustrate a functional interaction between BNN27 and the DAergic system that may be of relevance for schizophrenia-like behavioural symptoms.

Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: Emphasis on the modulation of oxidative stress and neuroinflammation

Chemotherapy-induced cognitive dysfunction (chemobrain) is one of the major complaints for cancer patients treated with chemotherapy such as Doxorubicin (DOX). The induction of oxidative stress and neuroinflammation were identified as major contributors to such adverse effect. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound, that exhibits unique context-dependent antioxidant activity. It exhibits pro-oxidant effects in cancer cells, while it is a potent antioxidant and cytoprotective in normal cells. The present study was designed to investigate the potential neuroprotective effects of CAPE against DOX-induced cognitive impairment. Chemobrain was induced in Sprague Dawley rats via systemic DOX administration once per week for 4 weeks (2 mg/kg/week, i.p.). CAPE was administered at 10 or 20 μmol/kg/day, i.p., 5 days per week for 4 weeks. Morris water maze (MWM) and passive avoidance tests were used to assess learning and memory functions. Oxidative stress was evaluated via the colorimetric determination of GSH and MDA levels in both hippocampal and prefrontal cortex brain regions. However, inflammatory markers, acetylcholine levels, and neuronal cell apoptosis were assessed in the same brain areas using immunoassays including either ELISA, western blotting or immunohistochemistry. DOX produced significant impairment in learning and memory as indicated by the data generated from MWM and step-through passive avoidance tests. Additionally DOX-triggered oxidative stress as evidenced from the reduction in GSH levels and increased lipid peroxidation. Treatment with DOX resulted in neuroinflammation as indicated by the increase in NF-kB (p65) nuclear translocation in addition to boosting the levels of pro-inflammatory mediators (COX-II/TNF-α) along with the increased levels of glial fibrillary acid protein (GFAP) in the tested tissues. Moreover, DOX reduced acetylcholine levels and augmented neuronal cell apoptosis as supported by the increased active caspase-3 levels. Co-treatment with CAPE significantly counteracted DOX-induced behavioral and molecular abnormalities in rat brain tissues. Our results provide the first preclinical evidence for CAPE promising neuroprotective activity against DOX-induced neurodegeneration and memory deficits.

Effects of estrogen deprivation on memory and expression of related proteins in ovariectomized mice.

BackgroundThe ovariectomized (OVX) rodent model is most widely used for studying the influence of estrogen deprivation on memory. However, the results of these studies are inconsistent, in that the memory of OVX rodents shows either impairment or no change. These inconsistent outcomes increase the difficulty of researching neurochemical mechanisms and evaluating drug efficacy. One possible explanation for these discrepancies might be that the time point for memory examination after OVX varies considerably among studies. The aim of our study was to investigate the effects of estrogen deprivation on memory and the expression of memory-related proteins at different times after OVX.MethodsNovel object recognition (NOR), step-through passive avoidance (STPA) and the Morris water maze (MWM) were performed to evaluate the memory performance of mice at different times after OVX. The expressions of BDNF, TrkB, ULK1 and LC3II/LC3I in the hippocampus were also assessed to explore the relevant mechanisms.ResultsAfter OVX, a significant memory impairment was found in the STPA test at 4 weeks. In the NOR and MWM tests, however, memory deficits were not observed until 8 weeks post-OVX. Interestingly, at 8 weeks, a memory rebound was found in the STPA test. In the hippocampus, the levels of BDNF and TrkB in OVX mice were markedly decreased at 4 and 8 weeks. Subsequently, a significant decrease in the ULK1 and LC3II/LC3I level in OVX mice was observed at 8 weeks.ConclusionsMemory impairment in mice was observed as early as 4 weeks after OVX, although there was a possibility of memory rebound with the prolongation of estrogen deprivation. Eight weeks of estrogen deprivation would be more likely to induce hippocampus-dependent memory impairment. This progressive impairment of memory might be due to the downregulation of the BDNF/TrkB signaling pathway at the early post-OVX stage, while the decrease of autophagy level in the later stage might also contribute to these progressive alterations. The underlying relationship between the BDNF/TrkB signaling pathway and autophagy in this progressive impairment of memory requires further study.