Behavioural impairments after exposure of neonatal mice to propofol are accompanied by reductions in neuronal activity in cortical circuitry.

BACKGROUND: Both animal and retrospective human studies have linked extended and repeated general anaesthesia during early development with cognitive and behavioural deficits later in life. However, the neuronal circuit mechanisms underlying this anaesthesia-induced behavioural impairment are poorly understood. METHODS: Neonatal mice were administered one or three doses of propofol, a commonly used i.v. general anaesthetic, over Postnatal days 7-11. Control mice received Intralipid® vehicle injections. At 4 months of age, the mice were subjected to a series of behavioural tests, including motor learning. During the process of motor learning, calcium activity of pyramidal neurones and three classes of inhibitory interneurones in the primary motor cortex were examined in vivo using two-photon microscopy. RESULTS: Repeated, but not a single, exposure of neonatal mice to propofol i.p. caused motor learning impairment in adulthood, which was accompanied by a reduction of pyramidal neurone number and activity in the motor cortex. The activity of local inhibitory interneurone networks was also altered: somatostatin-expressing and parvalbumin-expressing interneurones were hypoactive, whereas vasoactive intestinal peptide-expressing interneurones were hyperactive when the mice were performing a motor learning task. Administration of low-dose pentylenetetrazol to attenuate γ-aminobutyric acid A receptor-mediated inhibition or CX546 to potentiate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-subtype glutamate receptor function during emergence from anaesthesia ameliorated neuronal dysfunction in the cortex and prevented long-term behavioural deficits. CONCLUSIONS: Repeated exposure of neonatal mice to propofol anaesthesia during early development causes cortical circuit dysfunction and behavioural impairments in later life. Potentiation of neuronal activity during recovery from anaesthesia reduces these adverse effects of early-life anaesthesia.

Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses.

For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes. Phytocannabinoids are a family of compounds that are found in the cannabis plant, which is known for its psychotogenic and euphoric effects; the main psychotropic constituent of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC). The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body. Cannabis is used as a therapeutic agent for treating pain and emesis. Some cannabinoids are clinically applied for treating chronic pain, particularly cancer and multiple sclerosis-associated pain, for appetite stimulation and anti-emesis in HIV/AIDS and cancer patients, and for spasticity treatment in multiple sclerosis and epilepsy patients. Medical cannabis varies from recreational cannabis in the chemical content of THC and cannabidiol (CBD), modes of administration, and safety. Despite the therapeutic effects of cannabis, exposure to high concentrations of THC, the main compound that is responsible for most of the intoxicating effects experienced by users, could lead to psychological events and adverse effects that affect almost all body systems, such as neurological (dizziness, drowsiness, seizures, coma, and others), ophthalmological (mydriasis and conjunctival hyperemia), cardiovascular (tachycardia and arterial hypertension), and gastrointestinal (nausea, vomiting, and thirst), mainly associated with recreational use. Cannabis toxicity in children is more concerning and can cause serious adverse effects such as acute neurological symptoms (stupor), lethargy, seizures, and even coma. More countries are legalizing the commercial production and sale of cannabis for medicinal use, and some for recreational use as well. Liberalization of cannabis laws has led to increased incidence of toxicity, hyperemesis syndrome, lung disease cardiovascular disease, reduced fertility, tolerance, and dependence with chronic prolonged use. This review focuses on the potential therapeutic effects of cannabis and cannabinoids, as well as the acute and chronic toxic effects of cannabis use on various body systems.

The REACH registration process: A case study of metallic aluminium, aluminium oxide and aluminium hydroxide.

The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.

Fluoroquinolone prophylaxis does not increase risk of neuropathy in children with acute lymphoblastic leukemia.

BACKGROUND: Fluoroquinolone antibiotics are frequently utilized in pediatric oncology patients as prophylaxis or step-down therapy following broad spectrum beta-lactam therapy for febrile neutropenia. Concerns regarding neurotoxicity limit the use of these agents. No studies have evaluated the association between fluoroquinolone use and neurotoxicity in pediatric oncology patients receiving other neurotoxic agents such as vincristine. METHODS: An observational cohort study comprising patients aged 0-18 at diagnosis enrolled on a prospective study for treatment of acute lymphoblastic leukemia (ALL) at a pediatric comprehensive cancer center between October 2007 and November 2018. Data for neuropathic pain and sensory or motor neuropathy were collected prospectively, and a Cox proportional hazards regression model was used to evaluate associations between administration of fluoroquinolone antibiotics during induction therapy and subsequent development of vincristine-induced peripheral neurotoxicity (VIPN). RESULTS: A total of 598 participants were enrolled, including 338 (57%) who received fluoroquinolones during induction therapy; of these 470 (79%) were diagnosed with VIPN and 139 (23%) were diagnosed with high-grade (Grade 3+) VIPN. On unadjusted analyses, and analyses adjusted for age and race, there was no evidence of an association between fluoroquinolone exposure and subsequent VIPN (hazard ratio [HR] 0.8, 95% CI 0.5-1.04, P = .08) or high-grade VIPN (HR 1.1, 95% CI 0.4-2.2, P = .87). CONCLUSIONS: The results of this observational study do not show an association between exposure to fluoroquinolone antibiotics during induction therapy for ALL and subsequent development of vincristine-induced peripheral neuropathies, and suggest that a large increase in VIPN is unlikely.

25C-NBF, a new psychoactive substance, has addictive and neurotoxic potential in rodents.

The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg-1]; SA [0.01, 0.03, 0.1 mg kg-1]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg-1]; repeated high dose [4 × 8, 15, 30 mg kg-1]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.

L-carnitine supplementation as a potential therapy for suspected hyperammonaemic encephalopathy.

A 44-year-old female, with a background of cerebral palsy, epilepsy and learning disabilities, presented with multiple seizures and a persistently reduced consciousness level secondary to valproate-induced hyperammonaemic encephalopathy (plasma levels >50 µg/dl). Withdrawal of valproate and subsequent infusion of L-carnitine led to full recovery. Nonhepatic hyperammonaemia has been shown to be effectively treated by intravenous L-carnitine therapy by a series of case reports. To date, no randomised controlled trials have demonstrated this. Hyperammonaemic encephalopathy is possibly a more common presentation than expected that is currently underdiagnosed and exacerbated by valproate.

Gestational and Lactational Exposure to Malathion Affects Antioxidant Status and Neurobehavior in Mice Pups and Offspring.

Environmental factors such as pesticides are considered key determinants of brain damage and brain dysfunction. In the present work, we investigated the effect of an organophosphate pesticide, i.e., malathion, administrated peri- and postnatally on the antioxidant system as well as on acetylcholine esterase (AChE) activity in the brains of mice pups during the three postnatal weeks. Furthermore, we analyzed the behavior of the offspring just after weaning to assess the eventual effect of the pesticide on anxiety traits and social interaction. Concerning the biochemical biomarkers, the continuous treatment with malathion given either at a low dose of 5 mg/kg or at a medium one, 15 mg/kg, causes alterations in the activities of catalase, superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, accompanied by high level of peroxidation of membrane lipids, indicating a disturbance in intracellular redox homeostasis with subsequent increased intracellular oxidative stress. The effect was more pronounced when the high dose was applied. This was also demonstrated for the activity of AChE, downregulated at all postnatal ages investigated (5, 15, and 21), whereas the low dose (5 mg/kg) did not alter this enzymatic activity which is in line with the absence of locomotor activity alteration as assessed by open field (OF). With regard to this last test, results obtained show also that the treated offspring mice develop an anxiogenic state as evidenced by open field as well as an impairment of social interaction. Altogether, these results provide an accurate characterization of the association between neurobehavioral outcomes and brain alterations following malathion administrated in gestational and lactational periods, even given at low dose, classified as safe, and indicate clearly that the developing brain is sensitively vulnerable to this organophosphate pesticide.

Krill oil protects PC12 cells against methamphetamine-induced neurotoxicity by inhibiting apoptotic response and oxidative stress.

Methamphetamine (METH) exposure can cause severe effects to the nervous system; however, the underlying molecular mechanism of neurotoxicity caused by METH is still unclear. Oxidative stress and apoptosis are linked in the pathophysiology of many neurodegenerative diseases. Krill oil (KO) benefits human health via its strong antioxidant ability. Therefore, we hypothesized that KO supplementation might effectively prevent METH-induced neurotoxicity via the inhibition of apoptotic responses and oxidative damages. In this study, PC12 cells were exposed to both METH (3 mmol/L) and KO (0.1, 0.2, 0.4, 0.8 µg/mL) in vitro for 24 h, and the following parameters were measured to detect apoptosis and oxidative stress responses that were triggered by METH: cell viability, the oxidative enzyme system, NO production, ROS production, apoptosis, mitochondrial membrane potential and protein expression of cleaved caspase-3. The results indicate that KO mitigates the apoptotic response post-METH exposure in PC 12 cells by increasing cell viability, decreasing protein expression of cleaved caspase-3, reducing apoptotic rates, and decreasing dissipation of mitochondrial membrane potential. In addition, the study revealed increases in SOD and GSH activity, and decreases in MDA content, NO and ROS production, suggesting that KO is beneficial in reducing oxidative stress, which may also play a role in the regulation of METH-triggered apoptotic response. Consequently, these data indicate that KO could potentially alleviate METH-induced neurotoxicity via the reduction of apoptotic responses and oxidative damages.

Reversal of behavioral decline and neuropathology by a complex vitamin supplement involves modulation of key neurochemical stressors.

Metal ions are crucial for normal neurochemical signaling and perturbations in their homeostasis have been associated with neurodegenerative processes. Hypothesizing that in vivo modulation of key neurochemical processes including metal ion regulation (by transferrin receptor-1: TfR-1) in cells can improve disease outcome, we investigated the efficacy of a complex vitamin supplement (CVS) containing B-vitamins and ascorbic acid in preventing/reversing behavioral decline and neuropathology in rats. Wistar rats (eight weeks-old) were assigned into five groups (n = 8), including controls and those administered CVS (400 mg/kg/day) for two weeks before or after AlCl3 (100 mg/kg)-induced neurotoxicity. Following behavioral assessments, prefrontal cortex (PFC) and hippocampus were prepared for biochemical analyses, histology and histochemistry. CVS significantly reversed reduction of exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety. These correlated with CVS-dependent modulation of TfP-1 expression that were accompanied by significant reversal of neural oxidative stress in expressed superoxide dismutase, nitric oxide, catalase, glutathione peroxidase and malondialdehyde. Furthermore, CVS inhibited neural bioenergetics dysfunction, with increased labelling of glucokinase within PFC and hippocampus correlating with increased glucose-6-phosphate dehydrogenase and decreased lactate dehydrogenase expressions. These relates to inhibition of over-expressed acetylcholinesterase and increased total protein synthesis. Histological and Nissl staining of thin sections corroborated roles of CVS in reversing AlCl3-induced neuropathology. Summarily, we showed the role of CVS in normalizing important neurochemical molecules linking concurrent progression of oxidative stress, bioenergetics deficits, synaptic dysfunction and cellular hypertrophy during neurodegeneration.

Comparing the Effects of Ferulic Acid and Sugarcane Aqueous Extract in In Vitro and In Vivo Neurotoxic Models.

Molecules exhibiting antioxidant, neuroprotective, and regulatory properties inherent to natural products consumed by humans are gaining attention in biomedical research. Ferulic acid (FA) is a phenolic compound possessing antioxidant and cytoprotective properties. It is found in several vegetables, including sugarcane, where it serves as the main antioxidant component. Here, we compared the antioxidant and cytoprotective effects of FA with those of the total sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers of cell dysfunction in rat cortical brain slices and markers of physiological stress in Caenorhabditis elegans upon exposure to toxins evoking different mechanisms of neurotoxicity, including direct oxidative stress and/or excitotoxicity. In rat cortical slices, FA (250 and 500 µM), but not SCAE (~ 270 µM of total polyphenols), prevented the loss of reductive capacity induced by the excitotoxin quinolinic acid (QUIN, 100 µM), the pro-oxidant agent ferrous sulfate (FeSO4, 25 µM), and the dopaminergic pro-oxidant 6-hydroxydopamine (6-OHDA, 100 µM). In wild-type (N2) C. elegans, FA (38 mM) exerted protective effects on decreased survival induced by FeSO4 (15 mM) and 6-OHDA (25 mM), and the motor alterations induced by QUIN (100 mM), FeSO4, and 6-OHDA. In contrast, SCAE (~ 13.5 mM of total polyphenols) evoked protective effects on the decreased survival induced by the three toxic agents, the motor alterations induced by FeSO4, and the reproductive deficit induced by FeSO4. In addition, FA was unable to reverse the decreased survival induced by all these toxins in the skn-1-/- strain (VC1772), which lacks the homolog of mammalian Nrf2, a master antioxidant gene. Altogether, our results suggest that (1) both FA and SCAE afford protection against toxic conditions, (2) not all the effects inherent to SCAE are due to FA, and (3) FA requires the skn-1 pathway to exert its protective effects in C. elegans.

Inflammatory and oxidative mechanisms potentiate bifenthrin-induced neurological alterations and anxiety-like behavior in adult rats.

Bifenthrin (BF) is a synthetic pyrethroid pesticide widely used in several countries to manage insect pests on diverse agricultural crops. Growing evidence indicates that BF exposure is associated with an increased risk of developing neurodegenerative disorders. However, the mechanisms by which BF induces neurological and anxiety alterations in the frontal cortex and striatum are not well known. The present in vivo study was carried out to determine whether reactive oxygen species (ROS)-mediated oxidative stress (OS) and neuroinflammation are involved in such alterations. Thirty-six Wistar rats were thus randomly divided into three groups and were orally administered with BF (0.6 and 2.1 mg/kg body weight, respectively) or the vehicle (corn oil), on a daily basis for 60 days. Results revealed that BF exposure in rats enhanced anxiety-like behavior after 60 days of treatment, as assessed with the elevated plus-maze test by decreases in the percentage of time spent in open arms and frequency of entries into these arms. BF-treated rats also exhibited increased oxidation of lipids and carbonylated proteins in the frontal cortex and striatum, and decreased glutathione levels and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase. Treatment with BF also increased protein synthesis and mRNA expression of the inflammatory mediators cyclooxygenase-2 (COX-2), microsomal prostaglandin synthase-1 (mPGES-1) and nuclear factor-kappaBp65 (NF-kBp65), as well as the production of tumor necrosis factor-α (TNF-α) and ROS. Moreover, BF exposure significantly decreased protein synthesis and mRNA expression of nuclear factor erythroid-2 (Nrf2) and acetylcholinesterase (AChE), as well as gene expression of muscarinic-cholinergic receptors (mAchR) and choline acetyltransferase (ChAT) in the frontal cortex and striatum. These data suggest that BF induced neurological alterations in the frontal cortex and striatum of rats, and that this may be associated with neuroinflammation and oxidative stress via the activation of Nrf2/NF-kBp65 pathways, which might promote anxiety-like behavior.

Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.

Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

Prolonged toxicity from Kambo cleansing ritual.

Context: Kambo cleanse is a purification, cleansing ritual traditionally performed by South American shaman to confer luck and health to hunters. Case details: We report a patient who presented to the emergency department with prolonged symptoms of vomiting, flushing, facial swelling, altered mental status, and agitation requiring chemical restraints, 22 h after a Kambo cleanse. The patient was found with four small, circular, superficial burns to the ankle at the site where the resin was introduced. Discussion: The cleanse consists of rubbing resin obtained from the secretions of the giant leaf frog (Phyllomedusa bicolor) into superficial wounds to produce intense gastrointestinal symptoms followed by a sensation of increased stamina and strength. The cleanse is now being increasingly performed in Europe and USA.

A review of neurologic complications of biologic therapy in plaque psoriasis.

The use of biologic medications has represented a great advancement in the treatment of moderate to severe plaque psoriasis and has improved patients' quality of life. Despite the increasing popularity of biologics, their neurological side effects have been a constant concern. Reports of demyelinating diseases associated with tumor necrosis factor α (TNF-α) inhibitors continue to accumulate. Additionally, efalizumab was withdrawn from the market in 2009 for causing progressive multifocal leukoencephalopathy (PML). These reports highlight the need for dermatologists to inform patients of the risks and promote informed decision-making with patients prior to starting a biologic agent. Dermatologists also need to recognize early manifestations of neurologic side effects. This review provides an overview of the literature on neurologic diseases that have been found to be associated with biologic agents used for plaque psoriasis. Clinical presentations and diagnostic workups of such diseases are given to aid dermatologists in their early diagnosis and referral.

Development of the Adverse Outcome Pathway (AOP): Chronic binding of antagonist to N-methyl-d-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities of children.

The Adverse Outcome Pathways (AOPs) are designed to provide mechanistic understanding of complex biological systems and pathways of toxicity that result in adverse outcomes (AOs) relevant to regulatory endpoints. AOP concept captures in a structured way the causal relationships resulting from initial chemical interaction with biological target(s) (molecular initiating event) to an AO manifested in individual organisms and/or populations through a sequential series of key events (KEs), which are cellular, anatomical and/or functional changes in biological processes. An AOP provides the mechanistic detail required to support chemical safety assessment, the development of alternative methods and the implementation of an integrated testing strategy. An example of the AOP relevant to developmental neurotoxicity (DNT) is described here following the requirements of information defined by the OECD Users' Handbook Supplement to the Guidance Document for developing and assessing AOPs. In this AOP, the binding of an antagonist to glutamate receptor N-methyl-d-aspartate (NMDAR) receptor is defined as MIE. This MIE triggers a cascade of cellular KEs including reduction of intracellular calcium levels, reduction of brain derived neurotrophic factor release, neuronal cell death, decreased glutamate presynaptic release and aberrant dendritic morphology. At organ level, the above mentioned KEs lead to decreased synaptogenesis and decreased neuronal network formation and function causing learning and memory deficit at organism level, which is defined as the AO. There are in vitro, in vivo and epidemiological data that support the described KEs and their causative relationships rendering this AOP relevant to DNT evaluation in the context of regulatory purposes.

Comparative neurotoxicity study of mercury-based inorganic compounds including Ayurvedic medicines Rasasindura and Kajjali in zebrafish model.

Zebrafish behavioral model is a powerful tool for neuroscience research. Behavioral changes in the zebrafish are studied by administering drugs. With the aid of automated and open-source MATLAB program, high-accuracy tracking of zebrafish can be achieved, and the important behavioral parameters can be calculated. Although mercury is accepted as a potent neurotoxin, used as a key element for preparing certain Ayurvedic medicines. In this work, mercury-based inorganic compounds, including HgCl2, HgS, and Ayurvedic medicines (Rasasindura and Kajjali) were administrated in zebrafish, and the effects on various behavioral parameters and cortisol levels were studied. A significant change in the basic locomotor parameters of fish was observed including speed (43% reduction), meander (150% increment), and a number of freeze points (125% increment), during 5-day treatment of HgCl2 along with a 3-fold increase in cortisol level against the control groups. Abnormal behavior was also recorded in color preference test, and novel tank diving behavior of HgCl2-treated groups, which can be attributed to the neurotoxicity induced by the HgCl2 administration. Contrary to this, the Rasasindura-treated group showed a significant increase in speed by 33%, decrease in meander by 20%, decrease in freeze points by 30%, and insignificant alteration in cortisol levels, which can be related to the rejuvenating nature of the Ayurvedic medicine Rasasindura. Additionally, Kajjali treated group did not show any substantial changes in zebrafish cortisol level and behavioral parameters except one in the diving test that indicates lowering stress. Similarly, HgS group showed normal behaviors except two irregular motor behaviors identical with the HgCl2 group. From these results, it can be concluded that the mercury-based Ayurvedic Rasasindura and Kajjali did not show any adverse effect or toxicity on zebrafish behavior model.

Ilex paraguariensis: Potential antioxidant on aluminium toxicity, in an experimental model of Alzheimer's disease.

Ilex paraguariensis, yerba mate is a native plant from the southern region of Brazil. Studies showed that yerba mate has an antioxidant potential, which could help to reduce the risk of developing neurodegenerative diseases, as Alzheimer's Disease (AD). It's known that I. paraguariensis grows in acid soils with aluminium (Al), which is bioavailable in these soils. Al has a neurotoxic potential related with the progression of neurological disorders. This study aim was to evaluate the potential of I. paraguariensis in the etiology of AD using strains of Caenorhabditis elegans and the concentration of Al and antioxidants in the yerba mate extract. The results of the I. paraguariensis infusions made at 65°C and at 75° C show that there was no significant difference between both temperatures when preparing the tea infusion in relation to the presence of Al, methylxanthines, phenolic compounds and flavonoids. Additionally, in the case of Al, there was no difference between the extracts prepared at both temperatures. The behavioral parameters of C. elegans were altered after a long-term exposure to both factors: I. paraguariensis extract and Al. Through the antioxidant levels results along with the Al content on the Acetylcholinesterase (AChE) activity it is possible to observe that the acute and chronic exposure to Al and I. paraguariensis leaves extract are very similar to wild-type worms. Moreover, we can observe that the results in both the transgenic strains long-term exposed to I. paraguariensis leaves extract and to the Al concentrations presented an increase in the AChE activity.

Manganese Control of Glutamate Transporters' Gene Expression.

Manganese (Mn) is an essential trace element, serving as a cofactor for several enzymes involved in various cellular and biochemical reactions in human body. However, chronic overexposure to Mn from occupational or environmental sources induces a neurological disorder, characterized by psychiatric, cognitive, and motor abnormalities, referred to as manganism. Mn-induced neurotoxicity is known to target astrocytes since these cells preferentially accumulate Mn. Astrocytes are the most abundant non-neuronal glial cells in the brain, and they play a critical role in maintaining the optimal glutamate levels to prevent excitotoxic death. The fine regulation of glutamate in the brain is accomplished by two major glutamate transporters - glutamate transporter-1 (GLT-1) and glutamate aspartate transporter (GLAST) that are predominantly expressed in astrocytes. Excitotoxic neuronal injury has been demonstrated as a critical mechanism involved in Mn neurotoxicity and implicated in the pathological signs of multiple neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Recent evidences also establish that Mn directly deregulates the expression and function of both astrocytic glutamate transporters by decreasing mRNA and protein levels of GLT-1 and GLAST. Herein, we will review the mechanisms of Mn-induced gene regulation of glutamate transporters at the transcriptional level and their role in Mn toxicity.

Baicalein Protects against Rotenone-Induced Neurotoxicity through Induction of Autophagy.

Baicalein, a typical flavonoid compound, has neuroprotective properties in several neurological disorders. Autophagy plays a central role in maintaining the cellular homeostasis, and is involved in the pathogenesis of Parkinson's disease (PD). Recently, baicalein has been reported to induce autophagy. Therefore, the current study was designed to investigate whether baicalein could protect against rotenone-induced neurotoxicity via induction of autophagy both in SH-SY5Y cells and in a mouse model. A chronic PD mouse model was established by continuous intragastric administration of rotenone for 12 weeks. Baicalein was administrated from 7 to 12 week. Our results showed that baicalein prevented rotenone-induced behavioral deficits, dopaminergic neuronal loss, apoptosis and mitochondrial dysfunction. Furthermore, baicalein restored rotenone-impaired autophagy, and blocking the baicalein-induced autophagy using 3-methyladenine inhibited the neuroprotective effects of bacalein. Baicalein increased cell viability and restored mitochondrial function in SH-SY5Y cells. The beneficial effect of baicalein was abrogated by 3-methyladenine treatment. Furthermore, rapamycin increased autopahgy and reduced the rotenone-induced neurotoxicity in SH-SY5Y cells. Collectively, these results suggest that baicalein could prevent rotenone-induced neurotoxicity via restoring autophagy.

Acute toxic leukoencephalopathy associated with a non-prescription weight loss supplement: a report of two cases.

Weight loss dietary supplements are used with some frequency by an increasingly overweight population. Some products are not adequately regulated and may pose potential health risks. We report two new cases of acute toxic leukoencephalopathy (ATL) due to the use of a supplement marketed as a thermogenic weight loss aid. ATL is a heterogeneous clinic-radiological entity that has been associated with various compounds, such as chemotherapeutic drugs and immunomodulators. It is characterized by an often reversible periventricular and infratentorial demyelination. The commercialization of non-regulated weight loss products continues to be a health risk in our population.