EXPLORE THE IMPACT OF NOISE STRESS INDUCED BRAIN WAVE PATTERN AND BEHAVIOUR ALTERATIONS IN WISTAR ALBINO RATS

Objective: The aim of the study is to investigate the impact of noise-induced stress and electroencephalogram (EEG) with behavioral alteration in male Wistar albino Rats. Methods: Adult albino rats were randomly divided into three groups. Each group contains six animals. Rats exposed to acute and sub-acute noise, stress (100 dB/4 h) were compared with control animals and assessed for learning and memory using an Eight-arm radial maze, Y-maze, T-maze and also monitoring of brain electrical activity showed by the electro encephalography. Results: The reference memory and working memory error increases, in acute and sub-acute noise stress. The amplitude and frequency also increase in frontal and occipital lobar when compared to control animals. Conclusion: Animals were exposed to noise stress showed learning and memory impairment and also changes in EEG wave pattern.

Metacognition, cortical thickness, and tauopathy in aging

We investigated two aspects of metacognition and their relationship with cortical thickness and Alzheimer's Disease (AD) biomarkers, amyloid and tau, in cognitively healthy older adults (N=151). The two metacognition measures were self-appraisal rating of task performance and the difference between self-appraisal rating and actual task performance (appraisal discrepancy). All participants underwent neuropsychological testing and 1.5T structural MRI. A subset (N=66) received amyloid-PET with [11C] PiB and tau-PET with [18F] Flortaucipir. We found that worse performers had lower self-appraisal ratings, but still overestimated their performance, consistent with the Dunning-Kruger effect. Self-appraisal rating and appraisal discrepancy revealed distinct relationships with cortical thickness and AD pathology. Greater appraisal discrepancy, indicating overestimation, was related to thinning of inferior-lateral temporal, fusiform, and rostral anterior cingulate cortices. Lower self-appraisal was associated with higher entorhinal and inferior temporal tau. These results suggest that overestimation could implicate structural atrophy beyond AD pathology, while lower self-appraisal could indicate early behavioral alteration due to AD pathology, supporting the notion of subjective cognitive decline prior to objective deficits.

Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease

Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

Pharmacological Activity of Pyrazole Derivatives as an Anticonvulsant for Benefit against Epilepsy

<b><i>Introduction:</i></b> Pediatric patients with epilepsy are prone to cognitive impairments during growth and long-term use of most antiepileptic drugs (AED). The affected children do not respond to conventional AED and may require novel drugs to manage the disease. Valproic acid, a first-line drug to treat epilepsy, is associated with serious side effects, which precludes its wider use. Thus, in the present study, we intended to develop novel substituted pyrazoles. <b><i>Methods:</i></b> The molecules were tested for anticonvulsive activity in Swiss albino mice via maximal electroshock seizure and subcutaneous pentylenetetrazole assays. The most potent molecule among the class was further assayed for its effect on behavioral and CNS depressant activity. The effect of the most potent compounds was also analyzed on various indices of oxidative stress and inflammation in mice. <b><i>Results:</i></b> The designed compounds showed significant anticonvulsive activity in mice revealing 7h as the most potent anticonvulsive agent. The most potent anticonvulsant molecule 7h further showed no behavioral alteration and considerable CNS depressant activity. It also reduces the level of oxidative stress and inflammation in the mice. <b><i>Conclusion:</i></b> Our study demonstrated utility of pyrazole derivatives as anticonvulsants against epilepsy.

Ameliorative Potential of Glycyrrhiza glabra extracts on Memory Impairments in Stress Triggered Rats

Background: Glycyrrhiza glabra Linn. (Family: Fabaceae) has been known to very useful medicinal plant in the Traditional Medicinal Systems from the centuries. With ethnopharmacological values, it is well-reported plant for their traditional uses for anti-inflammatory, antioxidant, anxiolytic, expectorant activities, and antidepressant activities. Objective: Although it is described for memory enhancing activity, the present study was focused to examine the comparative effect of Glycyrrhiza glabra extracts viz. flavonoid rich (GGFE) and glycyrrhizin rich (GGGE) in stress triggered rats and to provide future research insight for this herbal drug, for which no scientific justification has been reported till now. Methods: Male Wister rats divided into 7 different groups (n= 6 per group) were given chronic foot-shock stress for 21 successive days with scheduled administration of the extracts (50 and 100 mg/kg) and standard drug (10 mg/kg) for 28 days. Elevated Plus Maze, Rectangular Maze, Morris Water Maze, and Locomotor activity were performed to test behavioral alteration and learning ability of stressed rats. Further, rats were sacrificed to assay acetylcholinesterase activity and antioxidant activity in brain samples for the mechanistic role in learning and memory. Results: Extracts of Glycyrrhiza glabra were indicated a significant alteration in stress induced learning and memory deficiency in behavioral parameters studied. These extracts were also modulated significant changes in acetylcholinesterase and antioxidant enzyme activity to improve the learning and memory of stressed rats. Conclusions: It is concluded that both extracts of Glycyrrhiza glabra (GGFE and GGGE) possess memory enhancing property in stress triggered rats. Moreover, these comparative results provided information and confirmed the high potential of GGGE in comparison to GGFE might be due to rich glycyrrhizin content present in GGGE responsible for acetylcholinesterase and antioxidant enzyme modulatory activity. Therefore, GGGE could be used as a promising lead for further mechanistic and molecular study for defining the role of glycyrrhizin of Glycyrrhiza glabra.

Neurodevelopmental Toxic Effects of Food Additives Used in Energy Drinks on Developing Rats

Background: Food additives are widely used in energy drinks and when taken above acceptable daily intake leads to various neurodevelopmental toxic effects. The present study aimed to evaluate the neurodevelopmental toxic effects in rat pups after pre and postnatal administration of selected food additives in pregnant animals. Methods: Pregnant rats aged 160-180 days were divided into six groups with four animals per group. Group 1 treated with vehicle, group 2 standard (caffeine 25 mg/kg p.o.), groups 3-6 were treated with glucuronolactone (5 mg/kg p.o.), taurine (8 mg/kg p.o.), gluconolactone (84 mg/kg p.o.), and combination of food additives respectively till postnatal day (PND) 15. After PND 21, pups were evaluated for neurobehavioural parameters using the behavioral alteration test, Morris water maze test, locomotor activity test, Y-maze test, hot plate latency and neurobehavioural scoring. Neurotransmitters were estimated in brain tissue extract on PND 30, 45 and 60 and histological observations were examined in the brain cortex region. Results: Food additive treated groups showed an increase in behavioral activity, escape latency, immobility, percentage of alterations, hot plate latency and neurobehavioural scoring at selected dose and combination compared to control (p<0.001). The decrease in neurotransmitter levels in the brain and marked degeneration of neurons in the cortex were observed significantly in group6 pups. Conclusion: The present results corroborate that food additives in combination induced neurodevelopmental toxic effects further mechanistic studies are suggested to understand the synergistic effect.

Atypical image presentation of X-linked adrenoleukodystrophy

Introduction: X-linked adrenoleukodystrophy (X-linked ADL-X) is the most common peroxisomal disorder affecting central nervous system, adrenal cortex and testicular functions. Central nervous system manifestations in X-linked adrenoleukodystrophy can be divided into 2 subcategories: cerebral forms that are associated with rapidly progressive inflammatory myelopathy and adrenomyeloneuropathy which is a non-inflammatory distal axonopathy. In the last quarter of the 20th century, the underlying mechanisms were described, including causal mutations of the ABCD1 gene in the disease. Clinical case: six year old male patient with adequate neurodevelopment, history of seizure at 2 years, origin unclear. At the age of 5, he develops motor symptoms of rapid progression. First consultation for hemiparesis of the left hemicuerpus, ataxic gait, behavioral alteration. During the following year he presents symptoms of rapid progression of motor involvement; dysarthria and quadriparesis, initially asymmetric neuroimages show a progression of the lesion finally compatible with ADL-X, which is confirmed with very long chain acids and spectroscopy. Conclusion: Radiological findings of asymmetric demyelination have rarely been described as a typical X-ALD presentation. A case with atypical radiological presentation is described to document other possibilities of radiological findings in this syndrome with metabolic involvement and to consider this type of presentation in the child population, avoiding delays in diagnosis and increased possibilities for treatment.

Evaluation of the Adverse Effects of Chronic Exposure to Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.

Evaluation of the Adverse Effects of Chronic Exposure of Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases of reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that the chronic waterborne exposure of DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.