Spontaneous Alternation Behavior Research Articles

Exploring animal protein sources against prevent age-related short-term memory decline in mice: Dietary fish (Alaska Pollock) protein exhibits superior protective effects.

Dietary factors, particularly proteins, have been extensively explored to combat cognitive impairment. We have previously reported that dietary fish (Alaska Pollock) protein (APP) is more effective than casein (CAS) or fish oil in maintaining short-term memory in senescence-accelerated mice prone 10 (SAMP10). To examine the specificity of the protective effect of APP intakes against short-term memory decline, we assessed the impact of various dietary animal proteins, including APP, CAS, chicken breast protein (CP), and whey protein (WP), against age-related cognitive function in SAMP10 mice. After feeding the experimental diets for 5 months, memory was assessed using the Y-maze. The APP group exhibited a significant increase in spontaneous alternation behavior as an indicator of working memory when group compared with groups fed with other protein source. Additionally, the APP group displayed significantly higher neurofilament heavy chain positivity than the CAS and CP groups, as evidenced immunohistochemical analysis. Gut microbiota analysis indicated that dietary APP significantly enhanced the relative abundance of Lactobacillus, which positively correlated with spontaneous alternation behavior. Collectively, these findings suggest that dietary APP is more effective than CAS, CP, or WP in preventing age-related short-term memory decline and morphological abnormalities in the hippocampal axons of SAMP10 mice. Moreover, APP-mediated improvements in cognitive deficits may be associated with changes in microbiota diversity. PRACTICAL APPLICATION: This research suggests that dietary fish protein from Alaska Pollock may be more efficient in prevention short-term memory decline in mice, compared to other animal proteins. This finding has practical implications for nutritional optimization, developing the new health food products, and elucidating the relationship between the impact of specific proteins on gut microbiota and prevention of age-related cognitive decline.

Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

The effects of chronic morphine administration on spatial memory and microtubule dynamicity in male mice's brain

The examination of the influence of morphine on behavioral processes, specifically learning and memory, holds significant importance. Additionally, microtubule proteins play a pivotal role in cellular functions, and the dynamics of microtubules contribute to neural network connectivity, information processing, and memory storage. however, the molecular mechanism of morphine on microtubule dynamics, learning, and memory remains uncovered. In the present study, we examined the effects of chronic morphine administration on memory formation impairment and the kinetic alterations in microtubule proteins induced by morphine in mice. Chronic morphine administration at doses of 5 and 10 mg/kg dose-dependently decreased subjects' performance in spatial memory tasks, such as the Morris Water Maze and Y-maze spontaneous alternation behavior. Furthermore, morphine was found to stabilize microtubule structure, and increase polymerization, and total polymer mass. However, it simultaneously impaired microtubule dynamicity, stemming from structural changes in tubulin dimer structure. These findings emphasize the need for careful consideration of different doses when using morphine, urging a more cautious approach in the administration of this opioid medication.

Cajanus cajan (L) Millsp seeds extract prevents rotenone-induced motor- and non-motor features of Parkinson disease in mice: Insight into mechanisms of neuroprotection

Ethnopharmacological relevanceCajanus cajan (L) Millsp (Fabaceae) seed decoction is used by traditional healers in Nigeria as nerve tonic, hence, could be beneficial in the treatment of Parkinson's disease (PD), a progressive and debilitating neurodegenerative disease that imposes great burden on the healthcare system globally. Aim of the studyThis study aimed at investigating the neuroprotective effect of ethanol seed extract of Cajanus cajan (CC) in the treatment of rotenone-induced motor symptoms and non-motor symptoms associated with PD. Materials and methodsTo assess the protective action of CC on rotenone-induced motor- and non-motor symptoms of PD, mice were first pretreated with CC (50, 100 or 200 mg/kg, p.o.) an hour before oral administration of rotenone (1 mg/kg, p.o, 0.5% in carboxyl-methylcellulose) for 28 consecutive days and weekly behavioural tests including motor assessment (open field test (OFT), rotarod, pole and cylinder tests) and non-motor assessment (novel object recognition (NOR), Y-maze test (YM), forced swim and tail suspension, gastric emptying and intestinal fluid accumulation tests) were carried out. The animals were euthanized on day 28 followed by the collection of brain for assessment of oxidative stress, inflammatory markers and immunohistochemical analysis of the striatum (STR) and substantia nigra (SN). Phytochemicals earlier isolated from CC were docked with protein targets linked with PD pathology such as; catechol-O-methyltransferase (COMT), tyrosine hydroxylase (TH) and Leucine rich receptor kinase (LRRK).Results: this study showed that CC significantly reduced rotenone-induced spontaneous motor impairment in OFT, pole, cylinder and rotarod tests in mice as well as significant improvement in non-motor features (significant reversal of rotenone-induced deficits discrimination index and spontaneous alternation behaviour in NORT and YM test, respectively, reduction in immobility time in forced swim/tail suspension test, gastrointestinal disturbance in intestinal transit time in mice. Moreso, rotenone-induced neurodegeneration, oxidative stress and neuroinflammation were significantly attenuated by CC administration. In addition, docking analysis showed significant binding affinity of CC phytochemicals with COMT, TH and LRRK2 receptors. ConclusionCajanus cajan seeds extract prevented both motor and non-motor features of Parkinson disease in mice through its antioxidant and anti-inflammatory effects. Hence, could be a potential phytotherapeutic adjunct in the management of Parkinson disease.

Betula pendula Leaf Extract Targets the Interplay between Brain Oxidative Stress, Inflammation, and NFkB Pathways in Amyloid Aβ1-42-Treated Rats.

Alzheimer's disease (AD) is known as the primary and most common cause of dementia in the middle-aged and elderly population worldwide. Chemical analyses of B. pendula leaf extract (BPE), performed using spectrophotometric and chromatographic methods (LC/MS), revealed high amounts of polyphenol carboxylic acids (gallic, chlorogenic, caffeic, trans-p-coumaric, ferulic, and salicylic acids), as well as flavonoids (apigenin, luteolin, luteolin-7-O-glucoside, naringenin, hyperoside, quercetin, and quercitrin). Four groups of Wistar rats were used in this experiment (n = 7/group): control (untreated), Aβ1-42 (2 μg/rat intracerebroventricular (i.c.v.), Aβ1-42 + BPE (200 mg/Kg b.w.), and DMSO (10 μL/rat). On the first day, one dose of Aβ1-42 was intracerebroventricularly administered to animals in groups 2 and 3. Subsequently, BPE was orally administered for the next 15 days to group 3. On the 16th day, behavioral tests were performed. Biomarkers of brain oxidative stress Malondialdehyde (MDA), (Peroxidase (PRx), Catalase (CAT), and Superoxid dismutase (SOD) and inflammation (cytokines: tumor necrosis factor -α (TNF-α), Interleukin 1β (IL-1β), and cyclooxygenase-2 (COX 2)) in plasma and hippocampus homogenates were assessed. Various protein expressions (Phospho-Tau (Ser404) (pTau Ser 404), Phospho-Tau (Ser396) (pTau Ser 396), synaptophysin, and the Nuclear factor kappa B (NFkB) signaling pathway) were analyzed using Western blot and immunohistochemistry in the hippocampus. The results show that BPE diminished lipid peroxidation and neuroinflammation, modulated specific protein expression, enhanced the antioxidant capacity, and improved spontaneous alternation behavior, suggesting that it has beneficial effects in AD.

Baclofen and 4-Phenylpyrrolidone Derivative GIZH-290 Attenuates Compulsive-Like Behavior in Mice

Obsessive-compulsive disorder (OCD) is a mental disease characterized by the obsessions which cause marked distress or anxiety and/or compulsions intended to alleviate this distress. The results of experimental and clinical studies suggest a possible role of GABAB receptors in the pathogenesis of OCD, making it relevant to study the effect of ligands of these receptors on the behavior of rodents. Objectives: Studying the effects of GIZH-290 and baclofen in animal models of OCD. Methods. The effects of GIZH-290 (0.01, 0.1, 1 mg/kg, i.p.) and baclofen (0.1, 1, and 5 mg/kg, i.p.) were studied in the marble burying test and the rotarod test, as well as in the 8-OH-DPAT-induced decrease in spontaneous alternation in mice. Results. Baclofen and GIZH-290 attenuated compulsive-like behavior in mice by reducing the number of buried marbles in the marble burying test at all tested doses. However, the effect of baclofen at a dose of 5 mg/kg was accompanied by a disruption of the animals’ motor coordination in the rotarod test. At the same time, neither baclofen nor GIZH-290 attenuated 8-OH-DPAT-induced (2 mg/kg, i.p.) decrease in spontaneous alternation behavior in mice. On the contrary, baclofen at a dose of 1 mg/kg exacerbated this disruption. Conclusion. Baclofen and GIZH-290 have anticompulsive activity in the marble burying test, but not in the 8-OH-DPAT-induced decrease in spontaneous alternation behavior in mice.

Curcumin alleviates Alzheimer’s disease by inhibiting inflammatory response, oxidative stress and activating the AMPK pathway

BackgroundAlzheimer’s disease (AD) is a common degenerative brain disorder with limited therapeutic options. Curcumin (Cur) exhibits neuroprotective function in many diseases. We aimed to explore the role and mechanism of Cur in AD. Materials and MethodsFirstly, we established AD mice by injecting amyloid-β1–42 (Aβ1–42) solution into the hippocampus. Then, the AD mice received 150 mg/kg/d Cur for 10 consecutive days. The Morris water maze test was conducted to evaluate the cognitive function of the mice by hidden platform training and probe trials. To assess the spatial memory of the mice, spontaneous alternation behavior, the number of crossing the novel arm and the time spent in the novel arm during the Y-maze test was recorded. Hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNAL) assay were performed to assess the pathological damage and apoptosis of brain tissues. The number of damaged neurons was inspected by Nissl staining. Immunohistochemical staining was then performed to detect Aβ1–42 deposition. The levels of tumor necrosis factor-α (TNF-a), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum and hippocampus, the contents of super oxide dismutase (SOD) and malondialdehyde (MDA) in brain tissues were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), RelA (p65) protein expressions and Adenosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation were tested using Western blot. ResultsCur not only improved cognitive function and spatial memory, but also alleviated the pathological damage and apoptosis of brain tissues for AD mice. Meanwhile, upon Cur treatment, the number of damaged neurons in AD mice was decreased, the level of Aβ1–42 in AD mice was significantly decreased. Furthermore, the AD mice treated with Cur exhibited lower TNF-a, IL-6, IL-1β and MDA levels and a higher SOD content. Besides, Cur also downregulated p65 expression and upregulated AMPK phosphorylation. ConclusionCur may improve AD via suppressing the inflammatory response, oxidative stress and activating the AMPK pathway, suggesting that Cur may be a potential drug for AD.

A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy.

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague-Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

A quantitative analysis of spontaneous alternation behaviors on a Y-maze reveals adverse effects of acute social isolation on spatial working memory

Animals tend to alternate between different choices, which requires the ability to remember recent choices. The Y-maze spontaneous alternation test is widely used in various animal models for assessing short-term memory, and its precise evaluation depends upon the accurate determination of the arm visit sequence. However, an objective method for defining arm visits is lacking owing to uncertainty regarding the extent to which an animal must go into the arm to be considered visited. Here, we conducted quantitative analyses on mice behavior in the Y-maze while systematically varying the arm visit threshold and assessed the effect of acute social isolation on spatial working memory. Our results revealed that 24-h social isolation significantly reduced spontaneous alternation rate when the arm threshold was set at the distal part of the arm. Furthermore, the memory of the recently visited arms faded away faster in the socially isolated mice. However, other behavioral factors were comparable to those of the group-housed mice, indicating a specific impairment of short-term memory. Our findings suggest that the location of arm visit threshold is critical for the precise evaluation of short-term memory, and our study provides a method for comprehensively and systematically assessing spontaneous alternation behavior in the Y-maze.

Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine-induced cognitive impairment.

Chronic exposure to methamphetamine (METH) causes severe and persistent cognitive impairment. The present study aimed to investigate the role of dynorphin/κ opioid receptor (KOR) system in the development of METH-induced cognitive impairment. We found that mice showed significant cognitive impairment in the novel object recognition test (NOR) following daily injections of METH (10mg/kg) for seven consecutive days. Systemic blockade of KOR prevented METH-induced cognitive impairment by pretreatment of the selective KOR antagonist norBNI (10mg/kg, i.p.) or KOR deletion. Then, significant increased dynorphin and KOR mRNA were observed exclusively in prelimbic cortex (PL) other than infralimbic cortex. Finally, microinjection with norBNI into PL also improved cognitive memory in METH-treated mice using NOR and spontaneous alternation behaviour test. Our results demonstrated that dynorphin/KOR system activation in PL may be a possible mechanism for METH-induced cognitive impairment and shed light on KOR antagonists as a potential neuroprotective agent against the cognitive deficits induced by drug abuse.

Systemic Administration of Porphyromonas Gingivalis Lipopolysaccharide Induces Glial Activation and Depressive-Like Behavior in Rats.

Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions. Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) injection protocols. The rats received an intraperitoneal injection of saline or Pg-LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas. The FST immobility time in the Pg-LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the Pg-LPS group compared to the sham group. The peripheral administration of Pg-LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. Pg-LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3. The major result of this study is that a repeated systemic administration of Pg-LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.

Chronic corticosterone improves perseverative behavior in mice during sequential reversal learning

BackgroundStressful life events can both trigger development of psychiatric disorders and promote positive behavioral changes in response to adversities. The relationship between stress and cognitive flexibility is complex, and conflicting effects of stress manifest in both humans and laboratory animals. ObjectiveTo mirror the clinical situation where stressful life events impair mental health or promote behavioral change, we examined the post-exposure effects of stress on cognitive flexibility in mice. MethodsWe tested female C57BL/6JOlaHsd mice in the touchscreen-based sequential reversal learning test. Corticosterone (CORT) was used as a model of stress and was administered in the drinking water for two weeks before reversal learning. Control animals received drinking water without CORT. Behaviors in supplementary tests were included to exclude non-specific confounding effects of CORT and improve interpretation of the results. ResultsCORT-treated mice were similar to controls on all touchscreen parameters before reversal. During the low accuracy phase of reversal learning, CORT reduced perseveration index, a measure of perseverative responding, but did not affect acquisition of the new reward contingency. This effect was not related to non-specific deficits in chamber activity. CORT increased anxiety-like behavior in the elevated zero maze test and repetitive digging in the marble burying test, reduced locomotor activity, but did not affect spontaneous alternation behavior. ConclusionCORT improved cognitive flexibility in the reversal learning test by extinguishing prepotent responses that were no longer rewarded, an effect possibly related to a stress-mediated increase in sensitivity to negative feedback that should be confirmed in a larger study.

Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.

The effect of 5-HT1A receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior. 8-OH-DPAT-induced decrease in spontaneous alternation behavior in Y-maze in mice with habituation and food reward is the most suitable procedure for experimental modeling of the perseverative behavior and studying the anticompulsive activity of new substances.

Differential binding of CREB and REST/NRSF to NMDAR1 promoter is associated with the sex-selective cognitive deficit following postnatal PBDE-209 exposure in mice.

Neonatal exposure to decabromodiphenyl ether (PBDE-209), a widely used flame retardant, affects cognitive performances in the later stage of life in a sex-dependent manner. PBDE-209 interferes with glutamatergic signaling and N-methyl-D-aspartate receptor (NMDAR) subunits with unresolved regulatory mechanisms. This study exposed male and female mice pups through postnatal day (PND) 3-10 to PBDE-209 (oral dose: 0, 6, or 20mg/kg body weight). The frontal cortex and hippocampus, collected from neonate (PND 11) and young (PND 60) mice, were analyzed for cAMP response element-binding protein (CREB) and RE1-silencing transcription factor/ Neuron-restrictive silencer factor (REST/NRSF) binding to NMDAR1 promoter and expression of NMDAR1 gene by electrophoretic mobility shift assay and semi-quantitative RT-PCR respectively. Behavioral changes were assessed using spontaneous alternation behavior and novel object recognition tests in young mice. In neonates, the binding of CREB was increased, while REST/NRSF was decreased significantly to their cognate NMDAR1 promoter sequences at the high dose of PBDE-209 in both the sexes. This reciprocal pattern of CREB and REST/NRSF interactions correlates with the up-regulation of NMDAR1 expression. Young males followed a similar pattern of CREB and REST/NRSF binding and NMDAR1 expression as in neonates. Surprisingly, young females did not show any alteration when compared to age-matched controls. Also, we found that only young males showed working and recognition memory deficits. These results indicate that early exposure to PBDE-209 interferes with CREB- and REST/NRSF-dependent regulation of the NMDAR1 gene in an acute setting. However, long-term effects persist only in young males that could be associated with cognitive impairment.

A high‐salt diet induces synaptic loss and memory impairment via gut microbiota and butyrate in mice

A high‐salt diet induces synaptic loss and memory impairment via gut microbiota and butyrate in mice

RETRACTED ARTICLE: Evaluating the neuroprotective effect of Spirulina platensis–loaded niosomes against Alzheimer’s disease induced in rats

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss, changes in behavior, and avoidance of social bonds. Aluminum is one of the main risk factors in the development of AD. Spirulina platensis (SP) is a microalga that improves motor and cognitive skills and prevents cerebral endothelial damage. SP could be delivered in a more controlled and targeted manner using nanoparticles like niosomes. The purpose of this research was to develop a SP-loaded niosome (SPLN) formulation as a drug delivery system to investigate the effectiveness and toxicity of SP as an AD therapy using the AlCl3-induced AD rat model. A niosomal formulation that consists of Tween 60, cholesterol, and dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation. AD was induced in rats by orally administering AlCl3. Compared with the AlCl3 control, the group treated with the SPLN formulation showed enhancement of the recognition and working memories by increasing the difference score, the discrimination ratio, and the spontaneous alternation behavior. Additionally, it revealed a significant increase in AchE genes, restored the reduced brain neurotransmitters, and improved brain oxidative status. In conclusion, SPLN formulation could be considered an effective AD therapy.

Influence of Murraya koenigii extract on diabetes induced rat brain aging

Food supplements are used to improve cognitive functions in age-related dementia. This study was designed to determine the Murraya koenigii leaves' effect on Alloxan-induced cognitive impairment in diabetic rats and the contents of oxidative stress biomarkers, catalase, reduced glutathione, and glutathione reductase in brain tissue homogenates. Wistar rats were divided into seven groups (six rats per group). Group I received saline water (1 ml, p.o.), Diabetes was induced in Groups II-VII with Alloxan (120 mg/kg/p.o). Group III was provided with Donepezil HCl (2.5 mg/kg/p.o.), Group IV, V, VI, and VII with Murraya koenigii ethanol extract (200 and 400 mg/kg/p.o.) and aqueous extract (200 and 400 mg/kg/p.o.), respectively, for 30 days. Behavior, acetylcholinesterase (AChE) activity, oxidative stress status, and histopathological features were determined in the hippocampus and cerebral cortex. Administration of Murraya koenigii ethanolic and aqueous extracts significantly (P<0.05, P<0.001) increased the number of holes crossed by rats from one chamber to another. There was an increase in the (1) latency to reach the solid platform, (2) number of squares traveled by rats on the 30th day, and (3) percentage of spontaneous alternation behavior compared to the control group. Administration for successive days markedly decreased AChE activity (P<0.05), decreased TBARS level, and increased catalase, GSH, and GR levels. Murayya koenigii could be a promising food supplement for people with dementia. However, more research into sub-chronic toxicity and pharmacokinetic and pharmacodynamics interactions is essential.

Ameliorative effect of the oil components derived from sweet potato shochu on impaired short-term memory in mice after amyloid β25-35 injection

Sweet potato shochu oil is a by-product of shochu production and usually discarded although some physiological functions are considered. In this study, we investigated the effects of shochu oil on short-term memory using a murine model of spontaneous alternating behavior induced by the intracerebroventricular (ICV) administration of amyloid β25-35 (Aβ25-35). Mice were orally administered shochu oil for 15 days. Experiments with a Y-maze model revealed that the Aβ25-35 caused a significant decrease in spontaneous alternation behavior, and supplementation with shochu oil significantly improved this behavior. DNA microarray analysis revealed that the administration of shochu oil downregulated the expression of S100a9 and Ptgs2, which reportedly exacerbate amyloid β deposition in Alzheimer's disease. The administration of shochu oil upregulated the expression of Dnaja1 and PP2A, which is typically downregulated in Alzheimer's disease. These data suggest that shochu oil possible ameliorates on impaired short-term memory in mice after amyloid β25-35 injection, as indicated by its effects on improving spontaneous alternation behavior and modulating the expressions of related genes.

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aβ load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.