Alzheimer's disease (AD), a neurodegenerative disease, is diagnosed by impaired learning and memory in elderly individuals. Tectochrysin (TEC) is a flavonoid compound isolated from Alpinia Oxyphylla ...Miq., which has been traditionally used for the treatment of diarrhea, salivation, diuresis and dementia. In our study, model mice with AD induced by intracerebroventricular injection of Aβ1–42 were used to determine the role of TEC on memory retrieval. The results revealed that AD mice received intracerebroventricular injection of TEC (140 µg/kg) showed improved spatial memory performance and down-regulated expressions of β-secretase and accumulation of Aβ1–42 in brain tissues. TEC also decreased the concentration of malondialdehyde and total cholinesterase, and increased activities of both antioxidant superoxide dismutase and glutathione peroxidase in hippocampal and cortex. In addition, Aβ1–42 induced injury of neurons in hippocampal CA1 layer was rehabilitated in TEC treated mice. These findings highlight the beneficial role of TEC in amnestic mice induced by Aβ1–42 through the down-regulation of Aβ1–42 accumulation, oxidative stress, and total cholinesterase. Our study indicated a therapeutic potential of TEC in the treatment of AD.
Highlights • The zebrafish is a popular novel model in pharmacogenetics and neuropharmacology. • Both larval and adult zebrafish models contribute to studying complex brain disorders. • Zebrafish are ...highly sensitive to major classes of clinically active neurotropic drugs. • Zebrafish models emerge as a useful tool for genetic screening and drug discovery.
•Ethological approach helps to understand the housing effects on rodent behaviors.•Effect of isolation rearing depends on social relationships with cagemates when isolated.•Isolation rearing during ...critical developmental period induces behavioral agitation.•Short-term isolation rearing disrupts social transmission of information between cagemates.
The aim of the present review is to discuss how housing conditions affect behavioral performance in laboratory rodents from an ethological view. Commonly used laboratory rodents such as rats and mice, are originally captured animals that largely retain species-typical natural behaviors, while have fully adapted to a laboratory setting after long-term domestication. Laboratory settings including caging and artificial group housing are a considerable ethological factor influencing rodents’ behaviors in commonly employed behavioral test paradigms, including emotional and defensive behaviors, learning and memory, and attention-related behaviors. Particularly, isolation rearing, single-housed in a cage, is referred to a deprivation of social relationships with cagemates, has a substantial impact on behavioral performance in laboratory rodents. In this review, we will fully examine the importance of caging related ethological factors, e.g., social relationships and its deprivation, which are essential for unraveling the nature of housing effect in laboratory rodents. These discussions regarding the housing conditions will provide valuable information for appropriately conducting behavioral studies and interpreting data of rodents’ behaviors in neuroscience.
Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural ...regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl-d-aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.
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•α2δ-1 is involved in regulating depression like behaviors induced by CUMS, which may be an important target for CLD exert to antidepressant effects.
•Mango seed kernel waste is not a problem, it is an economic resource.•Kernels extract improved memory and cognitive performance in amnesic mice.•Isolation and quantification of the major phenolics ...that significantly reduced amyloid β−42 and acetylcholinesterase levels.
The seed kernel wastes generated during the consumption and processing of Mangifera indica L. are generally discarded although their remarkable nutritional phytoconstituents. Aqueous methanol kernel extract was subjected to chromatographic and spectroscopic analyses for the isolation of predominant phenolic compounds. In addition, they were quantitatively estimated through HPLC. The isolates were characterized as gallic acid, mangiferin, isomangiferin, and 1,2,3,4,6-penta-O-galloyl-β-glucose and quantified as 37.48, 40.41, 33.29, and 69.07 mg/g extract, respectively. For the first time, the extract, as well as isomangiferin and pentagalloyl glucose were orally administered for 7 consecutive days in a lipopolysaccharide-induced-neuroinflammatory Alzheimer's disease mouse model for assessment of memory and cognitive performance. Isomangiferin (50 mg/kg) and pentagalloyl glucose (30 mg/kg) increased spatial recognition in the object recognition test by 45.34% and 47.62%, respectively, compared to Alzheimer's mice. Besides, they significantly improved the working memory (% alteration in the Y-maze test). Assessment of the mean amyloid β-42 concentrations revealed a significant reduction in animals treated with 50 & 100 mg/kg kernel extract (40.3 & 65.8%), 50 mg/kg isomangiferin (67.5%), and 30 mg/kg pentagalloyl glucose (57.25%) compared to the amnesic mice (increased by 276% compared to control). Also, a significant decrease for the same samples in acetylcholinesterase levels by 32.28%, 53.14%, 62.41%, and 57.9%, respectively, were detected compared to the Alzheimer's mice (increased by 88.75% compared to control). The neuroprotective effect of mango kernel extract and the isolates support their beneficial effects in restoring cognitive capabilities through anti-amyloid and anticholinesterase activities.
•Behavioral testing is indispensable for deepening our understanding of brain plasticity and in developing restorative therapies for stroke.•Here we review the most common behavioral tests used to ...assess sensorimotor impairment and recovery, cognition and mood in stroke animals.•Guidance is provided to help select the most appropriate behavioral tests to further improve translational success of experimental studies.
Functional recovery after an experimental stroke can be assessed by multiple behavioral tests, however, there is no consensus about which test to use in long-term stroke recovery studies or whether the tests are affected by stroke surgery, post-operative care or behavioral compensation due to repeated testing. This review describes the tests most commonly used to assess motor and sensorimotor function, cognition and mood in stroke animals. Although it is difficult to predict the direction of future research, it may be possible to prevent false-positive results by selecting an appropriate task or a battery of tasks. It is also expected that the upcoming stroke recovery recommendations and the improved dialogue between academy, industry and healthcare professionals will further promote translational success.
Intracerebral hemorrhage (ICH) is the second most common type of stroke and has one of the highest fatality rates of any disease. There are many clinical signs and symptoms after ICH due to brain ...cell injury and network disruption resulted from the rupture of a tiny artery and activation of inflammatory cells, such as motor dysfunction, sensory impairment, cognitive impairment, and emotional disturbance, etc. Thus, researchers have established many tests to evaluate behavioral changes in rodent ICH models, in order to achieve a better understanding and thus improvements in the prognosis for the clinical treatment of stroke. This review summarizes existing protocols that have been applied to assess neurologic function outcomes in the rodent ICH models such as pain, motor, cognition, and emotion tests. Pain tests include mechanical, hot, and cold pain tests; motor tests include the following 12 types: neurologic deficit scale test, staircase test, rotarod test, cylinder test, grid walk test, forelimb placing test, wire hanging test, modified neurologic severity score, beam walking test, horizontal ladder test, and adhesive removal test; learning and memory tests include Morris water maze, Y-maze, and novel object recognition test; emotion tests include elevated plus maze, sucrose preference test, tail suspension test, open field test, and forced swim test. This review discusses these assessments by examining their rationale, setup, duration, baseline, procedures as well as comparing their pros and cons, thus guiding researchers to select the most appropriate behavioral tests for preclinical ICH research.
Neurobehavioral toxicity of triclosan in mice Tabari, Shaghayegh Alizadeh; Esfahani, Mahsa Loran; Hosseini, Seyed Mohammad ...
Food and chemical toxicology,
08/2019, Letnik:
130
Journal Article
Recenzirano
Triclosan (TCS) is a broad-spectrum antibacterial compound which is used in many cosmetic products, medical devices and house hold products. Toxicity attributed to TCS has recently become a focus of ...research. Recent studies showed that TCS can easily migrate into the human brain and animal tissues and cause adverse changes in various target organs. Our knowledge of the neurotoxicity of TCS is largely based on very limited data. In this regard, adult male NMRI mice were administered TCS (1000, 2000, and 4000 mg/kg) by gavage for 14 consecutive days, whereas the control animals were given corn oil. At the end of the exposure, all mice were evaluated for locomotor activity, motor coordination and anxiety behaviors through the use of an open-field test, rotarod test, and elevated-plus maze (EPM) test, and for muscle strength in a grip strength test. A significant change in locomotor activity and coordination was observed in TCS treated mice. In parallel anxiety-like behaviors and muscle strength were affected by TCS. Haematoxylin-eosin staining also showed significant adverse effects in brain tissue of the TCS exposed mice. Based on these results, we conclude that a 14-day TCS exposure resulting in some behavioral disturbances in mice.
•Triclosan causes neurotoxic effect on mice brain.•Triclosan could induce anxiety like behaviors in mice.•Locomotor activity and motor coordination disturbed by Triclosan administration.•Significant adverse effects were observed in brain tissue of the Triclosan exposed mice.
Alzheimer's disease is becoming a growing problem increasing at a tremendous rate. Serotonin 5-HT6 receptors appear to be a particularly attractive target from a therapeutic perspective, due to their ...involvement not only in cognitive processes, but also in depression and psychosis. In this work, we present the synthesis and broad biological characterization of a new series of 18 compounds with a unique 1,3,5-triazine backbone, as potent 5-HT6 receptor ligands. The main aim of this research is to compare the biological activity of the newly synthesized sulfur derivatives with their oxygen analogues and their N-demethylated O- and S-metabolites obtained for the first time. Most of the new triazines displayed high affinity (Ki < 200 nM) and selectivity towards 5-HT6R, with respect to 5-HT2AR, 5-HT7R, and D2R, in the radioligand binding assays. For selected, active compounds crystallographic studies, functional bioassays, and ADME-Tox profile in vitro were performed. The exciting novelty is that the sulfur derivatives exhibit an agonistic mode of action contrary to all other compounds obtained to date in this chemical class herein and previously reported. Advanced computational studies indicated that this intriguing functional shift might be caused by presence of chalcogen bonds formed only by the sulfur atom. In addition, the N-demethylated derivatives have emerged highly potent antioxidants and, moreover, show a significant improvement in metabolic stability compared to the parent structures. The cholinesterase study present micromolar inhibitory AChE and BChE activity for both 5-HT6 agonist 19 and potent antagonist 5. Finally, the behavioral experiments of compound 19 demonstrated its antidepressant-like properties and slight ability to improve cognitive deficits, without inducing memory impairments by itself. Described pharmacological properties of both compounds (5 and 19) allow to give a design clue for the development of multitarget compounds with 5-HT6 (both agonist and antagonist)/AChE and/or BChE mechanism in the group of 1,3,5-triazine derivatives.
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•Synthesis of (thio)ether-1,3,5-triazine derivatives and their metabolites.•Radioligand binding assays for 5-HT6R, off-targets and enzymatic assays for ChEs.•X-ray crystallography and molecular modelling with emphasis on molecular dynamics.•Functional cAMP studies and drug-like profile in vitro.•Behavioral NOR, EPM, FST tests for the most active agent 19 in rats.
Uncertainty persists regarding the specific chemical causal factors and their corresponding behavioral effects in anxiety disorders. Commonly employed first-line treatments for anxiety target G ...protein-coupled receptors (GPCRs), including inhibitors of monoaminergic systems. Alternatively, emerging natural bioactive strategies offer potential for mitigating adverse effects. Recent investigations have implicated adenosine in anxiety-triggering mechanisms, while eritadenine, an adenosine analog derived from Shiitake mushroom, has displayed promising attributes. This study explores eritadenine's potential as a bioactive substance for anxiety disorders in mice, employing behavioral tests, pentobarbital-sleep induction, and molecular docking. Behavioral test results reveal a pronounced anxiolytic and sedative-hypnotic pharmacological effect of eritadenine. Our findings suggest that eritadenine may modulate locomotor functions mediated by adenosine receptors, with a stronger affinity for binding to A
AR over A
AR, thus eliciting these effects.
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