Acetylcholinesterase Enzyme Activity Research Articles

GABA-gated chloride channel mutation (Rdl) induces cholinergic physiological compensation resulting in cross resistance in Drosophila melanogaster

The Drosophila melanogaster MD-RR strain contains an Rdl mutation (A301S) resulting in resistance to several insecticide classes viz. phenyl pyrazoles (e.g., fipronil), cyclodienes (e.g., dieldrin), and chlorinated aliphatic hydrocarbons (e.g., lindane). Fitness costs are commonly observed with resistant insect populations as side effects of the genetic change conferring the resistant phenotype. Because of fitness costs, reversion from the resistant to susceptible genotype and phenotype is common. However, the Rdl genotype in D. melanogaster appears to allow the flies to maintain the resistant genotype/phenotype without selective pressure and with minimal fitness costs. We provide evidence that compensation for the Rdl mutation influences the cholinergic system, where an increase in acetylcholinesterase gene expression and enzyme activity results in neurophysiological changes and cross resistance to a carbamate insecticide (propoxur oral resistance ratio (RR) of 63) and an organophosphate insecticide (dichlorvos oral RR of 7). Such cross resistance was not previously reported with the initial collection and testing of this strain. In addition to acetylcholinesterase, the Rdl mutation influences the expression of the muscarinic acetylcholine receptor subtype-B, resulting in resistance to non-selective muscarinic compounds (pilocarpine and atropine). Collectively, these results indicate that the Rdl mutation (A301S) at GABA-gated ionophore complex influences the physiology of the cholinergic system, leading to resistance to established insecticide classes. Additionally, this mutation may impact the effectiveness of insecticides targeting novel sites, like muscarinic receptors.

Biochemical changes and bioaccumulation of manganese in Astyanax lacustris (Teleostei: Characidae).

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris.

Bioactivities of essential oil extracted from Elsholtzia densa Benth. And its main components against Tribolium castaneum eggs and pupae

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, β-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of β-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of β-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of β-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of β-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, β-caryophyllene, and limonene.

Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity.

The identification of novel acetylcholinesterase inhibitors holds significant relevance in the treatment of Alzheimer's disease (AD), the prevailing form of dementia. The exploration of alternative inhibitors to the conventional acetylcholinesterase inhibitors is steadily gaining prominence. Quinones, categorized as plant metabolites, represent a specific class of compounds. In this study, the inhibitory effects of various naphthoquinone derivatives, along with anthraquinone and its derivatives, on the acetylcholinesterase (AChE) enzyme were investigated for this purpose. An in vitro investigation was conducted to examine the effects of these compounds in order to clarify the possible mechanism of inhibition in the interaction between the enzyme and chemicals. In addition, an in silico investigation was carried out to understand the conceivable inhibitor binding process to the enzyme's active site. The acquired outcomes corroborated the in vitro results. The AChE enzyme was found to be effectively inhibited by both naphthoquinones and anthraquinones, with inhibition constant (KI) values ranging from 0.014 to 0.123μM (micormolar). The AChE enzyme was inhibited differently by this quinone and its derivatives. Although derivatives of naphthoquinone and anthraquinone exhibited a competitive inhibitory effect, derivatives of anthraquinone exhibited a noncompetitive inhibition effect. Furthermore, because it had the lowest KI value of any of these substances, 1,5-dihydroxyanthraquinone (1c) was shown to be the most potent inhibitor. The findings will add to the body of knowledge on the creation of fresh, potent, and successful treatment approaches.

Assessing the impact of antiviral drugs commonly utilized during the COVID-19 pandemic on the embryonic development of Xenopus laevis

The antiviral drugs favipiravir and oseltamivir are widely used to treat viral infections, including coronavirus 2019 (COVID-19), and their levels are expected to increase in the aquatic environment. In this study, the potential toxic and teratogenic effects of these drugs were evaluated using the frog embryo teratogenesis assay Xenopus (FETAX). In addition, glutathione S-transferase (GST), glutathione reductase (GR), catalase, carboxylesterase (CaE), and acetylcholinesterase (AChE) enzyme activities and malondialdehyde levels were measured as biochemical markers in embryos and tadpoles for comparative assessment of the sublethal effects of the test compounds. Prior to embryo exposure, drug concentrations in the exposure medium were measured with high-performance liquid chromatography. The 96-h median lethal concentration (LC50) was 137.9 and 32.3 mg/L for favipiravir and oseltamivir, respectively. The teratogenic index for favipiravir was 4.67. Both favipiravir and oseltamivir inhibited GR, CaE, and AChE activities in embryos, while favipiravir increased the GST and CaE activities in tadpoles. In conclusion, favipiravir, for which teratogenicity data are available in mammalian test organisms and human teratogenicity is controversial, inhibited Xenopus laevis embryo development and was teratogenic. In addition, sublethal concentrations of both drugs altered the biochemical responses in embryos and tadpoles, with differences between the developmental stages.

Evaluation of Changes in Acetylcholinesterase Activity in Workers of Mehriz Elixir Pesticide Plant in Yazd

Background and Aims: Some pesticide chemical compounds, such as organophosphates and carbamates, interfere with or inhibit cholinesterase activity. Employees working in pesticide factories are one of the groups at risk of pesticide poisoning. This study aimed to evaluate the effect of work on exposure to toxins on the serum level of erythrocyte cholinesterase activity.
 Materials and Methods: This research was conducted on Mehriz Elixir Pesticide Factory workers. Blood samples were taken from 76 employees in 2 groups as a control group, and 38 workers were exposed to organophosphorus toxins three months after starting work in a factory. Cholinesterase activity was analyzed using the Elman method, and data were analyzed using SPSS software version 22.
 Results: The mean age of the subjects was 35.07 years, which was 35.26 in the exposure group (n = 38) and 34.89 in the control group (n = 38). The activity of acetylcholinesterase enzyme in the control group at 0, 10, and 20 minutes was 12.78 ku/l, 14.24 ku/l, and 15.45 ku/l, respectively. The acetylcholinesterase enzyme activity in the exposed group was 10.77 ku/l, 10.40 ku/l, and 10.36 ku/l at 0, 10, and 20 minutes, respectively. At all stages, the mean acetylcholinesterase activity in the control group was higher than the exposed group, but significant differences were observed at 10 and 20 minutes between the 2 groups.
 Conclusion: Exposure of workers to organophosphate inhibits acetylcholinesterase, which manifests by a decrease in the activity of this enzyme.

Acetylcholinesterase enzyme among cancer patients a potential diagnostic and prognostic indicator a multicenter case–control study

Acetylcholinesterase enzyme (AChE) activity is impaired by a variety of inhibitors including organophosphorus pesticides, leading to the accumulation of acetylcholine. In this study, we aimed to determine the association between cancer and the blood level of the (AChE). This is a multicenter hospital-based case–control study conducted in the Radiation and Isotopes Center Khartoum, and Institute of Nuclear Medicine and Molecular Biology and Oncology Gezira. One hundred and fifty participants, half of them cancer patients and half cancer free were recruited. All participants were screened for demographic, environmental, occupational, and clinical characteristics. Blood for the (AChE) activity test was drawn from participants in the two groups. The mean age of the participants was 40.6 ± 14.8 years. Geographical distribution showed the Central Region of Sudan had the highest rate of cancer, followed by North State, Khartoum State, West State, and East State. The most common tumor subtype was breast cancer, followed by leukemia, colon, esophageal, and prostate cancer. Inferential analysis revealed significantly impaired (AChE) activity among cancer patients compared to controls (53.4 ± 20.3% vs. 93.8 ± 8.8, p-value 0.001). There was a significant statistical association between impaired (AChE) activity and cancer. (AChE) activity might be applied in the future as a diagnostic biomarker and therapeutic target. Further large sample and molecular studies are recommended.

Ace-1 Target Site Status and Metabolic Detoxification Associated with Bendiocarb Resistance in the Field Populations of Main Malaria Vector, Anopheles stephensi in Iran.

Anopheles stephensi is the main vector of malaria in Iran. This study aimed to determine the susceptibility of An. stephensi from the south of Iran to bendiocarb and to investigate biochemical and molecular resistance mechanisms in this species. Wild An. stephensi were collected from Hormozgan Province and reared to the adult stage. The susceptibility test was conducted according to the WHO protocols using bendiocarb impregnated papers supplied by WHO. Also, field An. Stephensi specimens were collected from south of Kerman and Sistan and Baluchistan Provinces. To determine the G119S mutation in the acetylcholinesterase (Ace1) gene, PCR-RFLP using AluI restriction enzyme and PCR direct-sequencing were performed for the three field populations and compared with the available GenBank data. Also, biochemical assays were performed to measure alpha and beta esterases, insensitive acetylcholinesterase, and oxidases in the strains. The bioassay tests showed that the An. stephensi field strain was resistant to bendiocarb (mortality rate 89%). Ace1 gene analysis revealed no G119S in the three field populations. Blast search of sequences revealed 98-99% identity with the Ace1 gene from Pakistan and India respectively. Also, the results of biochemical tests revealed the high activity of non-sensitive acetylcholinesterase, alpha and beta-esterase in the resistant strain compared to the susceptible strain. No G119S was detected in this study additionally the enhanced enzyme activity of esterases and acetylcholinesterase suggesting that resistance was metabolic. The use of alternative malaria control methods and the implementation of resistance management strategies are suggested in the study area.

Brain acetylcholinesterase activity and the protective effect of Gac fruit on scopolamine-induced memory impairment in adult zebrafish

Gac fruit (Momordica cochinchinensis) belongs to the Cucurbitaceae family. This study aimed to investigate the anti-memory impairment effect of Gac fruit aril extract and brain acetylcholinesterase activity in adult zebrafish (Danio rerio). The behavioral test was performed using a color-biased appetite conditioning T-maze test and an inhibitory avoidance test to evaluate memory performance. The time spent in the green arm in the T-maze test was recorded, and latency time was recorded in the inhibitory avoidance test. Brain acetylcholinesterase (AChE) enzyme activity was measured using a 96-well microplate reader based on Ellman's method. Zebrafish that received rivastigmine and Gac extract had significantly increased time spent in the green arm and latency time when compared to the SCO group. Zebrafish that received rivastigmine and Gac fruit extract at 200 mg/kg had lower AChE activity than the SCO groups; however, there were no statistically significant differences between the groups. These findings suggest that Gac fruit extract has anti-memory impairment activity and may be beneficial for the development of health products to prevent Alzheimer’s disease.

Protective Effect of Ferulic Acid on Acetylcholinesterase and Amyloid Beta Peptide Plaque Formation in Alzheimer's Disease: An In Vitro Study.

Aim This study aims to comprehensively evaluate the effects of ferulic acid (FA) on acetylcholinesterase (AChE) enzyme activity and amyloid beta (Aβ) peptide plaque formation in an in vitro model of Alzheimer's disease (AD). Background ADis a progressive neurological condition marked by disrupted cholinergic signaling, accumulation of Aβ peptide, and tau protein hyperphosphorylation. Currently, no direct anti-Alzheimer drug that effectively prevents the cognitive decline from AD has been reported. To combat this, a multi-target drug addressing several molecular aspects would be ideal for AD. Natural compounds are preferred over synthetic drugs due to their accessibility, cost-efficiency, and lower toxicity The proven association between polyphenolconsumption and the prevention of AD has led to the investigation of the effect of FA, a polyphenolic compound, on acetylcholinesterase enzyme activity and Aβ peptide formation, the key targets of AD. Materials and method The free radical scavenging ability of FA was assessed by xanthine oxidase inhibitory activity. Furthermore, FA was also evaluated for its inhibitory activity against AChE enzyme and amyloid beta peptide formation to evaluate the neuroprotective potential of FA. Results The results showed that FA has the potential to be an AChE inhibitor, thus helping in blocking the activity of AChE and also reducing the incidence of amyloid beta plaque formation. Furthermore, the compound also exhibited a significant antioxidant property which was demonstrated by the xanthine oxidase enzyme inhibitory effect. Conclusion From the observed results, FA has significant antioxidant and neuroprotective effects which are compared with those of their respective standards. More research is required to determine the efficacy and safety of this compound as a treatment for neurodegenerative diseases like AD because the precise mechanism and degree of its AChE inhibitory effects in the brain are still elusive. A potent, selective, and effective drug is desperately needed to treat patients with AD and those at risk of developing the disease.

Ixodicidal effect of extracts from Cordia boissieri, Artemisia ludoviciana and Litchi chinensis on Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

The ixodicidal activity of the methanolic extracts of Artemisia ludoviciana (Astereceae), Cordia boissieri (Boraginaceae) and Litchi chinensis (Sapindaceae) against two field populations of Rhipicephalus (Boophilus) microplus from the state of Nuevo Leon (NL) and Veracruz (VER) was evaluated. The extract of L. chinensis in the concentration of 150 mg/ml showed efficacies of 100% and 99% against engorged females and mortalities of 98% and 99% against larvae. C. boissieri in the same concentration showed efficacies of 71% and 37% against engorged adults and mortalities of 33.04% and 10.33% against larvae and A. ludoviciana had efficacies of 94% and 83% in adults and mortalities of 89.39% and 89.21% against larvae in both populations respectively. The enzymatic activity of Acetylcholinesterase (AChE), Carboxylesterase (CaE), Glutathione-S-Transferase (GST) and Alkaline Phosphatase (ALP) was measured in both populations of ticks. As a result, a significant difference between both populations was shown, being the VER population the one that exhibited a higher enzymatic activity (p ≤ 0.05). It can be concluded that the methanolic extract of the seed of L. chinensis shows potential ixodicidal activity and can be used as an alternative source of tick control, however, prior characterization, toxicity and formulation studies are necessary.

Evaluation of the Ecotoxicology of Seaweed-Based Biopesticide Used in Combat of the Polyphagous Pest Using Eudrilus eugeniae Kinb.

Fundamental techniques for determining the toxicity of pesticides to soil organisms are ecotoxicological laboratory assays. Due to their expanding potential and rise in use as a sustainable agricultural strategy toward the biological pest management, we quantified the effects of the compounds from the active fraction of the green seaweed Chaetomorpha antennina (Chlorophyceae), which is found in abundance in coastal areas of India that was used for the control of the polyphagous lepidopteran Spodoptera litura. Since the seaweed compounds were able to affect the morphology, physiology, and biochemical aspects of the pest, it is essential to perform an ecotoxicological assessment against the bioindicator organism Eudrilus eugeniae Kinb. This comprehensive assessment includes a morphological assay as well as the possible effects of the compounds on the earthworm's physiological and biochemical aspects such as acetylcholinesterase, catalase, and superoxide dismutase enzyme activities. The benignity of the compounds should also be confirmed by analyzing the gut histology of the earthworms treated with the compounds.

Protective effects of Embelin in Benzo[α]pyrene induced cognitive and memory impairment in experimental model of mice

Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.

A supercritical fluid co-extract of turmeric powder and dried coconut shreds shows neuroprotection against AlCl3-induced Alzheimer’s disease in rats through nose to brain delivery

This study was aimed at investigating the neuroprotective potential of a co-extract obtained by supercritical fluid extraction (SFE) of turmeric powder and dried coconut shreds against aluminium chloride (AlCl3)-induced Alzheimer's disease (AD) in male Wistar rats. Fifty animals were allocated to five groups, which received saline (vehicle control, group 1), a combination of saline and aluminium chloride (AlCl3) (disease control, group 2), coconut oil (COO) (SFE extracted, treatment group 3), turmeric oleoresin (Cur) (SFE extracted, treatment group 4) and SFE co-extract of turmeric powder and coconut shreds (CurCOO) (treatment group 5). Animals were subjected to behavioural evaluation. In addition, the hippocampal section of the brain from all groups was subjected to biochemical, molecular and histopathological evaluations. The results showed CurCOO administered intranasally improved cognitive abilities, reversed histological alterations in the brain, reduced hippocampus inflammation studied through proinflammatory cytokine markers like TNF-α and IL-6 as compared to the disease control group. The impact of CurCOO on preventive neurodegeneration was also observed through a reduction in protein transcription factor NF-kB in the treated group 5 as compared to a disease control group. The effect of intranasal delivery of CurCOO on the neurons responsible for memory consolidation was evident from low acetylcholinesterase (AChE) enzyme activity in the treated groups with respect to AlCl3 induced group. Summarily, the results demonstrated intranasal delivery of CurCOO to show better efficacy than Cur and COO in preventing neurodegeneration associated with AlCl3 induced Alzheimer’s disease.

Entomopathogenic fungi based microbial insecticides and their physiological and biochemical effects on Spodoptera frugiperda (J.E. Smith).

'The fall armyworm, Spodoptera frugiperda', represents a significant threat to maize production, a major staple crop in Asian countries. In pursuit of more effective control of this insect pest, our study assessed the physiological and biochemical effects of the entomopathogenic fungus Metarhizium anisopliae against the larvae of S. frugiperda. Results revealed that, following nine days of treatment, a high concentration of conidia (1.5x107 conidia/mL-1) was toxic to all stages of larvae (second to fifth instar), resulting in 97% mortality of the second instar, 89% mortality of the third instar, 77% mortality of the fourth instar, and 72% mortality of fifth instar. All larval instars were found to have dose-dependent mortality effects. Treated S. frugiperda larvae further displayed significant physiological, morphological, and behavioral changes. Here, treated larvae displayed significantly lower levels of acetylcholinesterase, α-carboxylesterase, and β-carboxylesterase enzyme activity when compared to control groups. Treated larvae underwent an outward morphological change as the result of a decrease in the exterior cuticle of the anal papillae and a demelanization of the interior cuticle. Treated larvae also exhibited abnormal feeding behaviors as a consequence of the negative impact of conidia treatment on the neuromuscular system. Investigation into the effect of M. anisopliae on the non-target organism, the earthworm Eudrilus eugeniae, revealed that M. anisopliae conidia did not produce significant pathogenicity following three days of treatment. Furthermore, histological analysis revealed no significant effect of the entomopathogenic fungi on the gut tissue of the non-target organism. This study highlights the potential of M. anisopliae in the control of S. frugiperda.

Tangeretin confers neuroprotection, cognitive and memory enhancement in global cerebral ischemia in rats.

Global cerebral ischemia is commonly associated with neurological deficits, including cognitive and memory impairments. The present study aims to investigate the neuroprotective, cognitive, and memory enhancement effects of Tangeretin, a flavonoid against global cerebral ischemia in rats. Bilateral common carotid artery occlusion (BCCAO) and reperfusion injury method was used to induce global cerebral ischemia in rats. Motor, cognitive, and memory functions were evaluated using rotarod, grip strength, Y-maze, and Morris water maze. Further, acetylcholine esterase (AchE) enzyme activity, acetylcholine (Ach), oxidative stress markers (ROS, SOD, MDA, and CAT), inflammation (IL-6 and TNF-α), and apoptotic markers (cytochrome C, caspase 9, and caspase 3) in BCCAO rats were measured following Tangeretin (5,10, and 20mg/kg, oral) treatment. Our findings show that Tangeretin treatment significantly improved cognition and memory by enhancing Ach levels through the amelioration of AchE enzyme activity in BCCAO rats. Moreover, Tangeretin exhibited neuroprotective effects through the mitigation of oxidative stress, inflammation, and apoptosis in the BCCAO rats. In summary, the current findings suggested that Tangeretin exhibited neuroprotection, cognitive and memory enhancement against global cerebral ischemia.

Using underwater currents as an occupational enrichment method to improve the stress status in rainbow trout.

This study investigated the effects of occupational enrichment, specifically underwater currents, on the stress status of rainbow trout (Oncorhynchus mykiss). A total of 540 fish were divided into three groups: control tanks without artificial currents (CO), tanks with randomly fired underwater currents (RFC), and tanks with continuous current throughout the day (CT). After 30days, half of the fish in each group underwent a 5-day pre-slaughter fasting (5D), while the others were fed until the day before slaughter (0D). Fish in the RFC group exhibited lower levels of plasma cortisol and acetylcholinesterase enzyme activity in hypothalamus and optic tract than other groups, suggesting an improved stress status. RFC group also showed higher levels of non-esterified fatty acids (NEFA) in 5D fish and higher liver glycogen stores, suggesting improved energy reserves. In comparison, the CT group had higher LDH levels, possibly due to their increased swimming activity. The CO group had significantly lower NEFA levels at 5D compared to the RFC group, suggesting lower energy reserves. The RFC fish had darker and yellow-reddish skin and liver color, suggesting an improved stress status and lower lipid reserves, respectively. Overall, although a significant stress response was not observed in fasted individuals, possibly due to the relatively short fasting period, the study suggests that providing occupational enrichment using randomly fired underwater currents for 1month helped to improve stress status in rainbow trout, indicating that occupational enrichment during the grow-out phase can positively impact the welfare of rainbow trout during routine handling procedures.

Low-dose exposure to malathion and radiation results in the dysregulation of multiple neuronal processes, inducing neurotoxicity and neurodegeneration in mouse

Neurodegenerative disorders are a debilitating and persistent threat to the global elderly population, carrying grim outcomes. Their genesis is often multifactorial, with a history of prior exposure to xenobiotics such as pesticides, heavy metals, enviornmental pollutants, ionizing radiation etc,. A holistic molecular insight into their mechanistic induction upon single or combinatorial exposure to different toxicants is still unclear. In the present study, one-month-old C57BL/6 male mice were administered orally with malathion (50 mg/kg body wt. for 14 days) and single whole-body radiation (0.5 Gy) on the 8th day. Post-treatment, behavioural assays for exploratory behaviour, memory, and learning were performed. After sacrifice, brains were collected for histology, biochemical assays, and transcriptomic analysis. Transcriptomic analysis revealed several altered processes like synaptic transmission and plasticity, neuronal survival, proliferation, and death. Signalling pathways like MAPK, PI3K-Akt, Apelin, NF-κB, cAMP, Notch etc., and pathways related to neurodegenerative diseases were altered. Increased astrogliosis was observed in the radiation and coexposure groups, with significant neuronal cell death and a reduction in the expression of NeuN. Sholl analysis, dendritic arborization and spine density studies revealed decreased total apical neuronal path length and dendritic spine density. Reduced levels of the antioxidants GST and GSH and acetylcholinesterase enzyme activity were also detected. However, no changes were seen in exploratory behaviour or learning and memory post-treatment. Thus, explicating the molecular mechanisms behind malathion and radiation can provide novel insights into external factor-driven neurotoxicity and neurodegenerative pathogenesis.

α-bisabolol β-d-fucopyranoside (ABFP) ameliorates scopolamine-induced memory deficits through cholinesterase inhibition and attenuation of oxidative stress in zebrafish (Danio rerio).

Alzheimer's disease (AD) is one of the major devastating neurodegenerative disorders associated with the gradual decline of an individual's memory, cognition, and ability to carry out day-to-day activities. In the present study, the neuroprotective ability of α-bisabolol β-d-fucopyranoside (ABFP) was assessed via measurement of antioxidant parameters like lipid peroxidation, glutathione peroxidation, glutathione, protein carbonyl content assays, and caspase-3 activity estimation. Moreover, the acute toxicity of ABFP was estimated in the zebrafish larval model. The results showed that ABFP exhibits little to no toxicity at lower concentrations in the acute toxicity test. ABFP-pretreated and scopolamine-exposed fish exhibited more exploratory behavior in the behavior assay than scopolamine-only induced groups. Additionally, the results of antioxidant enzyme assays revealed reduced oxidative stress and damage in ABFP-treated fish, while enzyme activity experiments carried out with brain homogenate from ABFP-treated fish showed decreased acetylcholinesterase enzyme activity. Overall, it can be concluded that ABFP has the potential to be a promising agent for the treatment of ADin the future.

Comprehensive Analysis of Titanium Oxide Nanoparticle Size and Surface Properties on Neuronal PC-12 Cells: Unraveling Cytotoxicity, Dopaminergic Gene Expression, and Acetylcholinesterase Inhibition.

Titanium oxide nanoparticles can penetrate the blood-brain barrier, infiltrate the central nervous system, and induce neurotoxicity. One of the most often utilized nanoparticles has been investigated for their neurotoxicity in many studies. Nonetheless, there remains an unexplored aspect regarding the comparative analysis of particles varying in size and nanoparticles of identical dimensions, both with and devoid of surface coating. In the current study, we synthesized two differently sized nanoparticles, TiO2-10 (10 nm) and TiO2-22 (22 nm), and nanoparticles of the same size but with a polyvinylpyrrolidone surface coating (TiO2-PVP, 22 nm) and studied their toxic effects on neural PC-12 cells. The results highlighted significant dose- and time-dependent cytotoxicity at concentrations ≥10 μg/mL. The exposure of TiO2 nanoparticles significantly elevated reactive oxygen and nitrogen species levels, IL-6 and TNF-α levels, altered the mitochondrial membrane potential, and enhanced apoptosis-related caspase-3 activity, irrespective of size and surface coating. The interaction of the nanoparticles with acetylcholinesterase enzyme activity was also investigated, and the results revealed a dose-dependent suppression of enzymatic activity. However, the gene expression studies indicated no effect on the expression of all six genes associated with the dopaminergic system upon exposure to 10 μg/mL for any nanoparticle. The results demonstrated no significant difference between the outcomes of TiO2-10 and TiO2-22 NPs. However, the polyvinylpyrrolidone surface coating was able to attenuate the neurotoxic effects. These findings suggest that as the TiO2 nanoparticles get smaller (towards 0 nm), they might promote apoptosis and inflammatory reactions in neural cells via oxidative stress, irrespective of their size.