Neurotoxic Effects Research Articles

Sensitive analysis of some detrimental volatile organic compounds in fabric, carpet and air freshener using solid phase extraction and gas chromatography–mass spectrometry

Benzene, toluene, ethylbenzene and xylene are known to be lethal environmental contaminants that have carcinogenic and mutagenic influences in human being while styrene and benzaldehyde have a neurotoxic effect. In other hand, the constituents of air freshener considered as a probable source of volatile organic compound. In the present work, a solid phase extraction and gas chromatography–mass spectrometry (GC-MS) technique has been optimized and applied to the fabric, carpet and air freshener samples to determine the trace amounts of benzene, toluene, ethylbenzene, xylene, styrene and benzaldehyde. The SupelcleanTM ENVITM - 18 cartridge with dichloromethane extracting solvent were found to be the optimal procedures. The system presented excellent performance in terms of limit of detection (0.08-0.61 ng/mL), coefficient of determination (0.994-0.997), precision with the relative standard deviation values ranging from 0.05-2.57%. According to the results, the concentration of benzene, toluene, ethylbenzene, xylene, styrene and benzaldehyde in fresheners’ samples was found in the range 0.03-53.27, 0.03-7.12, 0.02-6.51, 0.05-96.44, 0.04-7.06 and 0.22-23.02, respectively. The excellent recovery values were also obtained up to 99.93%. The SupelcleanTM ENVITM - 18 GC-MS system was found to appropriate for the monitoring of analytes in fabric, carpet, air freshener samples, and other samples of the similar constituents. KEY WORDS: BTEX, Styrene, Benzaldehyde, Air freshener, Solid phase extraction, Gas chromatography–mass spectrometry Bull. Chem. Soc. Ethiop. 2024, 38(6), 1543-1556. DOI: https://dx.doi.org/10.4314/bcse.v38i6.4

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

Activation of astrocytic NMDA receptors counteracted Aβ-induced reduction of BDNF and elevation of GFAP and complement 3 in the hippocampal astrocytes

N-methyl-D-aspartate receptors (NMDARs) play a crucial role in mediating Amyloid-β (Aβ) synaptotoxicity. Our previous studies have demonstrated an opposite (neuroprotection and neurotoxicity) effect of activating astrocytic and neuronal NMDARs with higher dose (10 μM) of NMDA, an agonist of NMDARs. By contrast, activating neuronal or astrocyitc NMDARs with lower dose (1 μM) of NMDA both exerts neuroprotective effect in Aβ-induced neurotoxicity. However, the underlying mechanism of activating astrocytic NMDARs with lower dose of NMDA to protect against Aβ neurotoxicity remains unclear. Based on our previous related work, in this study, using a co-cultured cell model of primary hippocampal neurons and astrocytes, we further investigated the possible factors involved in 1 μM of NMDA activating astrocytic NMDARs to oppose Aβ-induced synaptotoxicity. Our results showed that activation of astrocytic NMDARs by 1 μM NMDA rescued Aβ-induced reduction of brain-derived neurotrophic factor (BDNF), and inhibited Aβ-induced increase of GFAP, complement 3 (C3) and activation of NF-κB. Furthermore, blockade of astrocytic GluN2A with TCN201 abrogated the ability of 1 μM NMDA to counteract the effects of Aβ decreasing BDNF, and increasing GFAP, C3 and activation of NF-κB. These findings suggest that activation of astrocytic NMDARs protect against Aβ-induced synaptotoxicity probably through elevating BDNF and suppressing GFAP and C3. Our present research provides valuable insights for elucidating the underlying mechanism of astrocytic NMDARs activation resisting the toxic effects of Aβ.

Neurotoxic effects of perinatal exposure to Bisphenol F on offspring mice

Bisphenols constitute a diverse group of endocrine-disrupting chemicals (EDCs) that impact hormone activity. Bisphenol F (BPF) is commonly used as a substitute for Bisphenol A (BPA). The disruption of the immune system by EDCs during embryonic brain development has been suggested as a plausible factor to neurodevelopmental disorders. We investigated the neurotoxic effects of perinatal exposure to BPF on offspring mice. Female mice were exposed to BPF through their drinking water on day 0.5 of pregnancy, and this exposure continued until the offspring mice were weaned, throughout the perinatal period. Our findings revealed that exposure to BPF hindered both growth and neurodevelopment in offspring mice, with a more pronounced effect observed in males. Additionally, transcriptomic analysis was conducted on the brains of male offspring mice exposed to high doses of BPF. In summary, our study indicates that perinatal exposure to BPF results in neurodevelopmental impairments in male offspring mice, linked to oxidative stress, inflammatory responses, and immune dysregulation. These findings underscore that BPF may not be a safe substitute for BPA. Thus, there is a pressing need to reevaluate the current regulation of BPF.

Neurotoxicity, Neuroprotection, In Vitro MAOA/MAOB Inhibitory Activity Assessment, Molecular Docking, and Permeability Assay Studies of Newly Synthesized Hydrazones Containing a Pyrrole Ring.

Neurodegenerative diseases such as Parkinson's and Alzheimer's continue to be some of the most significant challenges in modern medicine. Recent research related to the molecular mechanisms of parkinsonism has opened up new approaches to antiparkinsonian therapy. In response to this, we present the evaluation of the potential neuroprotective and MAOA/MAOB inhibitory effects of newly synthesized hydrazones, containing a pyrrole moiety in the carboxyl fragment of the structure. The substances were studied on different brain subcellular fractions, including rat brain synaptosomes, mitochondria, and microsomes. The single application of 50 µM of each compound to the subcellular fractions showed that all substances exhibit a weak neurotoxic effect, with 7b, 7d, and 8d being the least neurotoxic representatives. The corresponding neuroprotective and antioxidant effects were also evaluated in different injury models on subcellular fractions, single out 7b, 7d, and 8d as the most prominent derivatives. A 1 µM concentration of each molecule from the series was also studied for potential hMAOA/hMAOB inhibitory effects. The results revealed a lack of hMAOA activity for all evaluated structures and the appearance of hMAOB effects, with compounds 7b, 7d, and 8d showing effects similar to those of selegiline. The best hMAOB selectivity index (>204) was determined for 7d and 8d, distinguishing these two representatives as the most promising molecules for further studies as potential selective MAOB inhibitors. The performed molecular docking simulations defined the appearance of selective MAOB inhibitory effects based on the interaction of the tested molecules with Tyr398, which is one of the components of the aromatic cage of MAOB and participated in π-π stabilization with the aromatic pyrrole ring. The preliminary PAMPA testing indicated that in relation to the blood-brain barrier (BBB) permeability, the tested pyrrole-based hydrazones may be considered as high permeable, except for 8a and 8e, which were established to be permeable in the medium range with -logP of 5.268 and 5.714, respectively, compared to the applied references.

Neurotoxic Effects of Mixtures of Perfluoroalkyl Substances (PFAS) at Environmental and Human Blood Concentrations.

Per- and polyfluoroalkyl substances (PFAS) may cause various deleterious health effects. Epidemiological studies have demonstrated associations between PFAS exposure and adverse neurodevelopmental outcomes. The cytotoxicity, neurotoxicity, and mitochondrial toxicity of up to 12 PFAS including perfluoroalkyl carboxylates, perfluoroalkyl sulfonates, 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and hexafluoropropylene oxide-dimer acid (HPFO-DA) were tested at concentrations typically observed in the environment (e.g., wastewater, biosolids) and in human blood using high-throughput in vitro assays. The cytotoxicity of all individual PFAS was classified as baseline toxicity, for which prediction models based on partition constants of PFAS between biomembrane lipids and water exist. No inhibition of the mitochondrial membrane potential and activation of oxidative stress response were observed below the cytotoxic concentrations of any PFAS tested. All mixture components and the designed mixtures inhibited the neurite outgrowth in differentiated neuronal cells derived from the SH-SY5Y cell line at concentrations around or below cytotoxicity. All designed mixtures acted according to concentration addition at low effect and concentration levels for cytotoxicity and neurotoxicity. The mixture effects were predictable from the experimental single compounds' concentration-response curves. These findings have important implications for the mixture risk assessment of PFAS.

Resolving Coffee Waste and Water Pollution-A Study on KOH-Activated Coffee Grounds for Organophosphorus Xenobiotics Remediation.

This study investigates using KOH-activated coffee grounds (KACGs) as an effective adsorbent for removing organophosphorus xenobiotics malathion and chlorpyrifos from water. Malathion and chlorpyrifos, widely used as pesticides, pose significant health risks due to their neurotoxic effects and environmental persistence. Spent coffee grounds, abundant biowaste from coffee production, are chemically activated with KOH to enhance their adsorptive capacity without thermal treatment. This offers a sustainable solution for biowaste management and water remediation. Adsorption kinetics indicating rapid initial adsorption with high affinity were observed, particularly for chlorpyrifos. Isotherm studies confirmed favorable adsorption conditions, with higher maximum adsorption capacities for chlorpyrifos compared to malathion (15.0 ± 0.1 mg g-1 for malathion and 22.3 ± 0.1 mg g-1 for chlorpyrifos), highlighting its potential in mitigating water pollution. Thermodynamic analysis suggested the adsorption process was spontaneous but with the opposite behavior for the investigated pesticides. Malathion interacts with KACGs via dipole-dipole and dispersion forces, while chlorpyrifos through π-π stacking with aromatic groups. The reduction in neurotoxic risks associated with pesticide exposure is also shown, indicating that no more toxic products were formed during the remediation. This research contributes to sustainable development goals by repurposing biowaste and addressing water pollution challenges through innovative adsorbent materials.

Brain and Serum Membrane Vesicle (Exosome) Profiles in Experimental Alcohol-Related Brain Degeneration: Forging the Path to Non-Invasive Liquid Biopsy Diagnostics

Background: Alcohol-related brain degeneration (ARBD) is associated with cognitive–motor impairments that can progress to disability and dementia. White matter (WM) is prominently targeted in ARBD due to chronic neurotoxic and degenerative effects on oligodendrocytes and myelin. Early detection and monitoring of WM pathology in ARBD could lead to therapeutic interventions. Objective: This study examines the potential utility of a non-invasive strategy for detecting WM ARBD using exosomes isolated from serum. Comparative analyses were made with paired tissue (Tx) and membrane vesicles (MVs) from the temporal lobe (TL). Methods: Long Evans rats were fed for 8 weeks with isocaloric liquid diets containing 37% or 0% caloric ethanol (n = 8/group). TL-Tx, TL-MVs, and serum exosomes (S-EVs) were used to examine ethanol’s effects on oligodendrocyte glycoprotein, astrocyte, and oxidative stress markers. Results: Ethanol significantly decreased the TL-Tx expression of platelet-derived growth factor receptor alpha (PDGFRA), 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNPase), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), glial fibrillary acidic protein (GFAP), and 8-OHdG, whereas in the TL-MVs, ethanol increased CNPase, PDGFRA, and 8-OHdG, but decreased MOG and GFAP concordantly with TL-Tx. Ethanol modulated the S-EV expression by reducing PLP, nestin, GFAP, and 4-hydroxynonenal (HNE). Conclusion: Chronic ethanol exposures differentially alter the expression of oligodendrocyte/myelin, astrocyte, and oxidative stress markers in the brain, brain MVs, and S-EVs. However, directionally concordant effects across all three compartments were limited. Future studies should advance these efforts by characterizing the relationship between ABRD and molecular pathological changes in brain WM-specific exosomes in serum.

Characteristics and Transcriptomic Analysis of Cholinergic Neurons Derived from Induced Pluripotent Stem Cells with APP Mutation in Alzheimer's Disease.

The cholinergic hypothesis is one of the main theories that describe the pathogenesis of Alzheimer's disease (AD). Cholinergic neurons degenerate early and are severely damaged in AD. Despite extensive research, the causes of cholinergic neuron damage and the underlying molecular changes remain unclear. This study aimed to explore the characteristics and transcriptomic changes in cholinergic neurons derived from human induced pluripotent stem cells (iPSCs) with APP mutation. Peripheral blood mononuclear cells from patients with AD and healthy individuals were reprogrammed into iPSCs. The iPSCs were differentiated into cholinergic neurons. Cholinergic neurons were stained, neurotoxically tested, and electrophysiologically and transcriptomically analyzed. The iPSCs-derived cholinergic neurons from a patient with AD carrying a mutation in APP displayed enhanced susceptibility to Aβ1-42-induced neurotoxicity, characterized by severe neurotoxic effects, such as cell body coagulation and neurite fragmentation. Cholinergic neurons exhibited electrophysiological impairments and neuronal death after 21 days of culture in the AD group. Transcriptome analysis disclosed 883 differentially expressed genes (DEGs, 420 upregulated and 463 downregulated) participating in several signaling pathways implicated in AD pathogenesis. To assess the reliability of RNA sequencing, the expression of 16 target DEGs was validated using qPCR. Finally, the expression of the 8 core genes in different cell types of brain was analyzed by the AlzData database. In this study, iPSCs-derived cholinergic neurons from AD patients with APP mutations exhibit characteristics reminiscent of neurodegenerative disease. Transcriptome analysis revealed the corresponding DEGs and pathways, providing potential biomarkers and therapeutic targets for advancing AD research.

Evaluating Health Risks Associated With Fluoride and Nitrate Contaminants in Drinking Water to Residents Living in the Chikkaballapur Taluk of Karnataka, India

ABSTRACTAddressing fluoride and nitrate contamination in groundwater is crucial for safeguarding public health. Fluoride contamination in groundwater can cause dental and skeletal fluorosis, along with potential neurotoxic effects. Nitrate contamination can lead to methemoglobinemia in infants and increase cancer risk due to the formation of nitrosamines. The major goal of this study was to examine groundwater quality in the Chickkaballapur urban (CBU) and Chikkaballapur rural (CBR) parts of the Chikkaballapur taluk (CBT), Karnataka, and to investigate the potential health hazards associated with the presence of fluoride and nitrate contaminants. Hazard quotient and total hazard index (THI) calculation methods, as suggested by the United States Environmental Protection Agency, were used in the present study to evaluate non‐carcinogenic risks for individuals of various age categories, including men, women, and children (MWC). A total of 112 samples from rural areas and 41 samples from urban areas of Chikkaballapur taluk were collected during the post‐monsoon season. According to the study's findings, groundwater samples from CBU and CBR surpassed acceptable fluoride concentration limits by 41% and 40%, respectively, while samples from CBR exceeded acceptable nitrate limits by 17%, set by the Bureau of Indian Standards (1 mg/L for fluoride and 45 mg/L for nitrate). All CBU samples remained within the acceptable nitrate limits. The total non‐carcinogenic health risks for MWC ranged from 0.34 to 2.18, 0.40 to 2.58, and 0.46 to 2.95, respectively, for CBU, and from 0.16 to 6.51, 0.19 to 7.69, and 0.21 to 8.80, respectively, for CBR. Furthermore, a significant percentage of the groundwater samples that were collected in CBU (60.98%, 68.29%, and 75.61%) and CBR (48.21%, 62.50%, and 73.21%) exceeded the THI limit for MWC (THI = 1). Hence, based on the health risk assessment, it is evident that children in the study area have greater health risks than men and women.

Changes in S100 calcium-binding protein β (S100β) and cognitive function from pre- to post-chemotherapy among women with breast cancer

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Evaluation of developmental milestones and of brain measurements in rats exposed to the pesticide pyriproxyfen in prenatal period.

Pyriproxyfen is a pesticide used in Brazil to control the Aedes aegypti mosquito, vector of arboviruses like Zika and dengue. However, this pesticide is structurally similar to retinoic acid, a metabolite of vitamin A that regulates neuronal differentiation and hindbrain development during the embryonic period. Due to the similarity between pyriproxyfen and retinoic acid, studies indicate that this pesticide may have cross-reactivity with retinoid receptors. Thus, pregnant exposure to pyriproxyfen could interfere in the nervous system development of the fetal. In this context, the present study evaluated whether prenatal exposure to pyriproxyfen affects neonatal development and brain structure in rats. Wistar rat pups were divided in three experimental groups: (1) negative control (CT-)-offspring of rats that drink potable water during pregnancy; (2) pyriproxyfen (PIR)-offspring of rats exposed to Sumilarv® prenatally, a pesticide that has pyriproxyfen as active ingredient; and (3) positive control (CT+)-offspring of rats exposed to an excess of vitamin A prenatally. Only vitamin A treated-pregnant showed lower weight gain, but gestation length was similar among pregnant that received potable water, water containing vitamin A and water containing Sumilarv. In relation to the offspring, PIR group exhibits a delayed front-limb suspension response but performed early the negative geotaxis reflex. On the other hand, CT+ group exhibited lower body weight in the 1st postnatal day, delayed audio startle response, but performed early the eyelids opening and hindlimb placing response. A reduction in the maximum brain width was observed both in PIR and CT+ groups, but a reduction in the number of neurons in the M1 cortex was showed only in CT+ group. The number of glial cells in this brain area was similar between the three experimental groups studied. Although prenatal exposure to pyriproxyfen did not alter neonatal milestones in the same way as vitamin A in excess, both substances caused a reduction in the maximum width of the brain, suggesting that this pesticide can produce neurotoxic effects during the embryonic period.

Curcumin's Neuroprotective Effects on the Neurons of the Rat Cerebrum's Motor Cortex against Tartrazine's Neurotoxic Effects

Curcumin's Neuroprotective Effects on the Neurons of the Rat Cerebrum's Motor Cortex against Tartrazine's Neurotoxic Effects

Analyzing the neurotoxic effects of anatoxin-a and saxitoxin in zebrafish larvae

Global warming due to climate change, as well as freshwater eutrophication caused by anthropogenic activities are responsible, among other factors, for an increasing occurrence of harmful algal blooms (HABs) in aquatic systems. These can lead to the generation of cyanotoxins, secondary metabolites coming from cyanobacteria, producing adverse effects in living organisms including death. This research aims to study the effects that two neurotoxins, anatoxin-a (ATX-a) and saxitoxin (STX), have on living organisms. Once the stability of both compounds in water was determined for a 24 h period using ultra-high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer (UPLC-MS/MS), zebrafish larvae were exposed to different levels of toxins (1 ng L−1, 10 ng L−1, 100 ng L−1 and 1 μg L−1) during 24 h. Behavioral studies including vibrational startle response (VSR), habituation to vibrational stimuli, basal locomotor activity (BLM) and visual motor response (VMR) were performed using Danio Vision system, and neurotransmitters (NTs) from 15-head pools of control and exposed zebrafish larvae were extracted and analyzed by UPLC-MS/MS. Both compounds induced hypolocomotion in the individuals, while 10 and 100 ng L−1 of ATX-a significantly increased methionine (120 % and 126 %, respectively) and glutamate levels (118 % and 129 %, respectively). Saxitoxin enhanced 3-metoxytyramine (3-MT) levels at 1 ng L−1 by 185 %. The findings of this study show that both studied cyanotoxins influence the behavior of zebrafish larvae as well as their metabolism.

Challenges and Opportunities for Consideration of Efavirenz Drug Repurposing for Alzheimer's Disease Therapeutics.

Therapeutic research and development for Alzheimer's disease (AD) has been an area of intense research to alleviate memory loss and neurodegeneration. There is growing interest in drug repositioning and repurposing strategies for FDA-approved medications as potential candidates that may further advance AD therapeutics. The FDA drug efavirenz has been investigated as a candidate drug for repurposing as an AD medication. The proposed mechanism of action of efavirenz (at low doses) is the activation of the neuron-specific enzyme CYP46A1 that converts excess brain cholesterol into 24-hydroxycholesterol (24-HC) that is exported to the periphery. Efavirenz at a low dose was found to improve memory deficit in the 5XFAD model of AD that was accompanied by elevated 24-HC and reduction in Aβ; furthermore, efavirenz reduced pTau and excess cholesterol levels in human iPSC-derived Alzheimer's neurons. The low dose of efavirenz used in the AD mouse model to increase 24-HC contrasts with the use of more than 100-fold higher doses of efavirenz for clinical treatment of human immunodeficiency virus (HIV) through inhibition of reverse transcriptase. Low doses of efavirenz may avoid neurotoxic adverse effects that occur at high efavirenz doses used for HIV treatment. This review evaluates the drug properties of efavirenz with respect to its preclinical data on regulating memory deficit, pharmacokinetics, pharmacodynamics, metabolites, and genetic variabilities in drug metabolism as well as its potential adverse effects. These analyses discuss the challenges and questions that should be addressed in future studies to consider the opportunity for low dose efavirenz as a candidate for AD drug development.

Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish (Danio rerio).

This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish (Danio rerio) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming.

Melatonin attenuates affective disorders and cognitive deficits induced by perinatal exposure to a glyphosate-based herbicide via antioxidant pathway in adult male and female rats.

The massive use of herbicides, particularly glyphosate-based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4mg/kg) from postnatal days 30-58. Our results show that GBH increases anxiety-like behavior levels in offspring, as well as depression-like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate-based pesticides. It will then be interesting to further our work to fully understand the sex-dependent effect of melatonin.

The Neuroprotective Effects of Agmatine on Parkinson's Disease: Focus on Oxidative Stress, Inflammation and Molecular Mechanisms.

Agmatine (AGM), a naturally occurring polyamine derived from L-arginine, has shown significant potential for neuroprotection in Parkinson's Disease (PD) due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. This review explores the therapeutic potential of AGM in treating PD, focusing on its neuroprotective mechanisms and evidence from preclinical studies. AGM has been demonstrated to mitigate the neurotoxic effects of rotenone (ROT) by improving motor function, reducing oxidative stress markers, and decreasing levels of pro-inflammatory cytokines in animal models. Additionally, AGM protects against the loss of TH + neurons, crucial for dopamine synthesis. The neuroprotective properties of AGM are attributed to its ability to modulate several key pathways implicated in PD pathogenesis, such as inhibition of NMDA receptors, activation of Nrf2, and suppression of the HMGB1/ RAGE/ TLR4/ MyD88/ NF-κB signaling cascade. Furthermore, the potential of agmatine to promote neurorestoration is highlighted by its role in enhancing neuroplasticity elements such as CREB, BDNF, and ERK1/2. This review highlights agmatine's promising therapeutic potential in PD management, suggesting that it could offer both symptomatic relief and neuroprotective benefits, thereby modifying the disease course and improving the quality of life for patients. Further research is warranted to translate these preclinical findings into clinical applications.

Microplastics in the Olfactory Bulb of the Human Brain

Microplastic (MP) pollution is an emerging environmental and health concern. While MPs have been detected in various human tissues, their presence in the human brain has not been documented, raising important questions about potential neurotoxic effects and the mechanisms by which MPs might reach brain tissues. To determine the presence of MPs in the human olfactory bulb and to analyze their characteristics such as size, morphology, color, and polymeric composition. This case series study used a cross-sectional design involving the analysis of olfactory bulb tissues obtained from deceased individuals during routine coroner autopsies. The sampling procedures were conducted at São Paulo City Death Verification Service, with laboratory analysis carried out at the Brazilian Synchrotron Light Laboratory (LNLS). Participants included 15 adult individuals who had been residents of São Paulo for more than 5 years and underwent coroner autopsies. Exclusion criteria included previous neurosurgical interventions. Data analysis was performed in April 2024. The primary exposure assessed was the presence of MPs in the olfactory bulb, analyzed through direct tissue examination and digested tissue filtration followed by micro-Fourier transform infrared spectroscopy. The main outcomes were the identification and characterization of MPs within the olfactory bulb, including their size, morphology, color, and polymeric composition. The median age of the 15 deceased individuals was 69.5 years, ranging from 33 to 100 years, with 12 males and 3 females. MPs were detected in the olfactory bulbs of 8 out of 15 individuals. A total of 16 synthetic polymer particles and fibers were identified, with 75% being particles and 25% being fibers. The most common polymer detected was polypropylene (43.8%). Sizes of MPs ranged from 5.5 μm to 26.4 μm for particles, and the mean fiber length was 21.4 μm. Polymeric materials were absent in procedural blank and negative control filters, indicating minimal contamination risk. This case series provides evidence of MPs found in the human olfactory bulb, suggesting a potential pathway for the translocation of MPs to the brain. The findings underscore the need for further research on the health implications of MP exposure, particularly concerning neurotoxicity and the potential for MPs to bypass the blood-brain barrier.

Neurotoxic effects associated with chronic inhalation and oral exposure to glyphosate-based herbicide IN adult rats.

The use of glyphosate-based herbicides (GBHs) for agricultural production has increased substantially around the world, as have their residues in the environment. Its effects on the central nervous system and neurotoxicity pathways are still not fully understood. The aim of this study was to evaluate the neurotoxic effect of chronic exposure to a GBH in adult rats. Sixty adult male albino Wistar rats were allocated into 6 groups, 2 control groups, and four GBH exposure groups (n=10/group). The animals were exposed to two concentrations of GBH, orally and by inhalation: 2.99 × 10-3grams of active ingredient per hectare (g.a.i./ha) and 7.48 × 10-3g.a.i./ha. The animals were exposed for six months. Behavioral studies were performed. Brain tissue was collected for histopathological, immunohistochemical, and oxidative stress analyses. Animals exposed by inhalation to GBH spent more time in the central area of the open field test, whereas animals exposed to a high oral concentration of GBH spent less time in the open arms in the elevated plus-maze test. Tissue hyperemia occurred only in animals exposed to high concentrations of GBH. There was a greater thickness of the cerebral cortex and an increase in the expression of the BCL-2 in the animals exposed by inhalation to GBH. There was no difference in the doses of malonaldehyde and protein carbonylation between exposed and unexposed groups. The exposure to GBH caused increased levels of anxiety, regardless of the route, high concentrations caused hyperemia and inhalation exposure cause increased cortex thickness and increased BCl-2 expression.