Current Aspects on the Plastic Nano- and Microparticles Toxicity in Zebrafish-Focus on the Correlation between Oxidative Stress Responses and Neurodevelopment.

Recent reports focusing on the extent of plastic pollution have shown that many types of fibers and polymers can now be found in most marine species. The severe contamination of plastic nano-/microparticles (NPs/MPs) mainly results in immediate negative outcomes, such as organic impairments and tissue damage, as well as long-termed negative effects, such as developmental retardation and defects, chronic inflammation, oxidative stress (OS), metabolic imbalance, mutagenesis, and teratogenesis. Oxidative responses are currently considered the first line molecular signal to potential toxic stimuli exposure, as the oxidative balance in electron exchange and reactive oxygen species signaling provides efficient harmful stimuli processing. Abnormal signaling or dysregulated ROS metabolism-OS-could be an important source of cellular toxicity, the source of a vicious cycle of environmental and oxidative signaling-derived toxicity. As chemical environmental pollutants, plastic NPs/MPs can also be a cause of such toxicity. Thus, we aimed to correlate the possible toxic effects of plastic NPs/MPs in zebrafish models, by focusing on OS and developmental processes. We found that plastic NPs/MPs toxic effects could be observed during the entire developmental span of zebrafish in close correlation with OS-related changes. Excessive ROS production and decreased antioxidant enzymatic defense due to plastic NPs/MPs exposure and accumulation were frequently associated with acetylcholinesterase activity inhibition, suggesting important neurodevelopmental negative outcomes (cognitive abnormalities, neurodevelopmental retardation, behavioral impairments) and extraneuronal effects, such as impaired digestive physiology.

A Review of the Most Recent Clinical and Neuropathological Criteria for Chronic Traumatic Encephalopathy.

(1) Background: Chronic traumatic encephalopathy (CTE) is a complex pathological condition characterized by neurodegeneration, as a result of repeated head traumas. Currently, the diagnosis of CTE can only be assumed postmortem. Thus, the clinical manifestations associated with CTE are referred to as traumatic encephalopathy syndrome (TES), for which diagnostic multiple sets of criteria can be used. (2) Objectives: In this study, we aimed to present and discuss the limitations of the clinical and neuropathological diagnostic criteria for TES/CTE and to suggest a diagnostic algorithm enabling a more accurate diagnostic procedure. (3) Results: The most common diagnostic criteria for TES/CTE discriminate between possible, probable, and improbable. However, several key variations between the available diagnostic criteria suggest that the diagnosis of CTE can still only be given with postmortem neurophysiological examination. Thus, a TES/CTE diagnosis during life imposes a different level of certainty. Here, we are proposing a comprehensive algorithm of diagnosis criteria for TES/CTE based on the similarities and differences between the previous criteria. (4) Conclusions: The diagnosis of TES/CTE requires a multidisciplinary approach; thorough investigation for other neurodegenerative disorders, systemic illnesses, and/or psychiatric conditions that can account for the symptoms; and also complex investigations of patient history, psychiatric assessment, and blood and cerebrospinal fluid biomarker evaluation.

Review on the Role of Salivary Biomarkers in the Diagnosis of Mild Traumatic Brain Injury and Post-Concussion Syndrome.

(1) Background: While mild traumatic brain injuries (TBIs) are a major public health issue, post-concussion syndrome (PCS) remains a controversial entity. In both cases, the clinical diagnosis is mainly based on the symptoms and brain imaging evaluation. The current molecular biomarkers were described from blood and cerebrospinal fluid (CSF), yet both fluid collection methods are invasive. Saliva could be preferred in molecular diagnosis due to its non-invasive and non-expensive methods of acquisition, transport, and samples processing. (2) Objectives: In the present study, we aimed to review the latest developments in salivary biomarkers and their potential role in diagnosing mild TBIs, and PCS. (3) Results: In TBIs and PCS, a few novel studies focusing on salivary biomarkers have emphasized their importance in diagnosis. The previous studies mainly focused on micro RNAs, and only a few on extracellular vesicles, neurofilament light chain, and S100B. (4) Conclusions: The combination between salivary biomarkers, clinical history and examination, self-reported symptoms, and cognitive/balance testing can provide a non-invasive alternative diagnostic methodology, as compared to the currently approved plasma and cerebrospinal fluid biomarkers.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish-Focussing on Neurobehavioural and Psychological Responses.

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species.

Pinus halepensis Essential Oil Ameliorates Aß1-42-Induced Brain Injury by Diminishing Anxiety, Oxidative Stress, and Neuroinflammation in Rats.

The Pinus L. genus comprises around 250 species, being popular worldwide for their medicinal and aromatic properties. The present study aimed to evaluate the P. halepensis Mill. essential oil (PNO) in an Alzheimer's disease (AD) environment as an anxiolytic and antidepressant agent. The AD-like symptoms were induced in Wistar male rats by intracerebroventricular administration of amyloid beta1-42 (Aß1-42), and PNO (1% and 3%) was delivered to Aß1-42 pre-treated rats via inhalation route for 21 consecutive days, 30 min before behavioral assessments. The obtained results indicate PNO's potential to relieve anxious-depressive features and to restore redox imbalance in the rats exhibiting AD-like neuropsychiatric impairments. Moreover, PNO presented beneficial effects against neuroinflammation and neuroapoptosis in the Aß1-42 rat AD model.

The Modulatory Effects of Non-Thermal Plasma on Seed's Morphology, Germination and Genetics-A Review.

Non-thermal plasma (NTP) is a novel and promising technique in the agricultural field that has the potential to improve vegetal material by modulating the expression of various genes involved in seed germination, plant immune response to abiotic stress, resistance to pathogens, and growth. Seeds are most frequently treated, in order to improve their ability to growth and evolve, but the whole plant can also be treated for a fast adaptive response to stress factors (heat, cold, pathogens). This review focuses mainly on the application of NTP on seeds. Non-thermal plasma treated seeds present both external and internal changes. The external ones include the alterations of seed coat to improve hydrophilicity and the internal ones refer to interfere with cellular processes that are later visible in metabolic and plant biology modifications. The usage of plasma aims to decrease the usage of fertilizers and pesticides in order to reduce the negative impact on natural ecosystem and to reduce the costs of production.

Mini-Review on the Harlequin Syndrome-A Rare Dysautonomic Manifestation Requiring Attention.

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

Biomolecules from Plant Wastes Potentially Relevant in the Management of Irritable Bowel Syndrome and Co-Occurring Symptomatology.

During and following the processing of a plant's raw material, considerable amounts are wasted, composted, or redistributed in non-alimentary sectors for further use (for example, some forms of plant waste contribute to biofuel, bioethanol, or biomass production). However, many of these forms of waste still consist of critical bioactive compounds used in the food industry or medicine. Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders. The primary treatment is based on symptomatology alleviation and controlled dietary management. Thus, this review aimed to describe the possible relevance of molecules residing in plant waste that can be used to manage IBS and co-occurring symptoms. Significant evidence was found that many forms of fruit, vegetable, and medicinal plant waste could be the source of some molecules that could be used to treat or prevent stool consistency and frequency impairments and abdominal pain, these being the main IBS symptoms. While many of these molecules could be recovered from plant waste during or following primary processing, the studies suggested that enriched food could offer efficient valorization and prevent further changes in properties or stability. In this way, root, stem, straw, leaf, fruit, and vegetable pomaces were found to consist of biomolecules that could modulate intestinal permeability, pain perception, and overall gastrointestinal digestive processes.

Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Danio rerio) Model of Alzheimer's Disease.

Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer's disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.

Memory-Enhancing Effects of Origanum majorana Essential Oil in an Alzheimer's Amyloid beta1-42 Rat Model: A Molecular and Behavioral Study.

Origanum L. (Lamiaceae) is an important genus of medicinal and aromatic plants used in traditional medicine since ancient times as culinary herbs and remedies. The aim of the present study was to evaluate the chemical composition, as well as the biochemical and cellular activities of freshly prepared Origanum majorana L. essential oil (OmEO) in an Alzheimer's disease (AD) amyloid beta1-42 (Aß1-42) rat model. OmEO (1% and 3%) was inhaled for 21 consecutive days, while Aß1-42 was administered intracerebroventricularly to induce AD-like symptoms. Our data demonstrate that OmEO increased antioxidant activity and enhanced brain-derived neurotrophic factor (BDNF) expression, which in concert contributed to the improvement of cognitive function of animals. Moreover, OmEO presented beneficial effects on memory performance in Y-maze and radial arm-maze tests in the Aß1-42 rat AD model.

Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aß25-35-Induced Rat Model of Alzheimer's Disease.

The nicotinic derivatives, cotinine (COT), and 6-hydroxy-L-nicotine (6HLN), showed promising cognitive-improving effects without exhibiting the nicotine's side-effects. Here, we investigated the impact of COT and 6HLN on memory impairment and the oxidative stress in the Aß25-35-induced rat model of Alzheimer's disease (AD). COT and 6HLN were chronically administered to Aß25-35-treated rats, and their memory performances were assessed using in vivo tasks (Y-maze, novel object recognition, and radial arm maze). By using in silico tools, we attempted to associate the behavioral outcomes with the calculated binding potential of these nicotinic compounds in the allosteric sites of α7 and α4ß2 subtypes of the nicotinic acetylcholine receptors (nAChRs). The oxidative status and acetylcholinesterase (AChE) activity were determined from the hippocampal tissues. RT-qPCR assessed bdnf, arc, and il-1ß mRNA levels. Our data revealed that COT and 6HLN could bind to α7 and α4ß2 nAChRs with similar or even higher affinity than nicotine. Consequently, the treatment exhibited a pro-cognitive, antioxidant, and anti-AChE profile in the Aß25-35-induced rat model of AD. Finally, RT-qPCR analysis revealed that COT and 6HLN positively modulated the bdnf, arc, and il-1ß genes expression. Therefore, these nicotinic derivatives that act on the cholinergic system might represent a promising choice to ameliorate AD conditions.

Ameliorative effects of Matricaria chamomilla L. hydroalcoholic extract on scopolamine-induced memory impairment in rats: A behavioral and molecular study.

BACKGROUND: Matricaria chamomilla L. is a medicinal herb traditionally used as the anti-inflammatory, antimicrobial, antiviral, anxiolytic and antidepressant agent. Nevertheless, supporting evidence demonstrated its memory enhancing activity and antioxidant properties. PURPOSE: To investigate the effects of the hydroalcoholic extract of M. chamomilla L. on memory processes in a scopolamine-induced a rat model of amnesia and to reveal its underlying mechanism of action. METHODS: The hydroalcoholic extract (25 and 75 mg/kg) was intraperitoneally administered to rats once daily for 7 days, and scopolamine (0.7 mg/kg) was injected 30 min before the behavioral testing to induce memory impairment. The phytochemical composition of the extract was quantified by HPLC/DAD analysis. Y-maze and radial arm-maze tests were employed for memory assessing. Acetylcholinesterase activity was measured in the rat hippocampus. Superoxide dismutase, glutathione peroxidase, and catalase specific activities along with the total content of reduced glutathione and protein carbonyl and malondialdehyde levels were also measured in the rat hippocampus. qRT-PCR was used to quantify BDNF mRNA and IL1ß mRNA expression in the rat hippocampus. RESULTS: We first identified the chlorogenic acid, apigenin-7-glucoside, rutin, cynaroside, luteolin, apigenin and derivatives of apigenin-7-glucoside as the extract major components. Furthermore, we showed that the extract reversed the scopolamine-induced decreasing of the spontaneous alternation in the Y-maze test and the scopolamine-induced increasing of the working and reference memory errors in the radial arm maze test. Also, the scopolamine-induced alteration of the acetylcholinesterase activity and the oxidant-antioxidant balance in the rat hippocampus was recovered by the treatment with the extract. Finally, we demonstrated that the extract restored the scopolamine-decreased BDNF expression and increased IL1ß expression in the rat hippocampus. CONCLUSION: These findings suggest that the extract could be a potent neuropharmacological agent against amnesia via modulating cholinergic activity, neuroinflammation and promoting antioxidant action in the rat hippocampus.

Lactuca capensis reverses memory deficits in Aß1-42-induced an animal model of Alzheimer's disease.

We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid-ß1-42 (Aß1-42). Behavioural assays such as Y-maze and radial arm maze test were used for assessing memory performance. Aß1-42 decreased cognitive performance in the behavioural tests which were ameliorated by pre-treatment with the methanolic extract. Acetylcholinesterase activity and oxidant-antioxidant balance in the rat hippocampus were abnormally altered by Aß1-42 treatment while these deficits were recovered by pre-treatment with the methanolic extract. In addition, rats were given Aß1-42 exhibited in the hippocampus decreased brain-derived neurotrophic factor (BDNF) mRNA copy number and increased IL-1ß mRNA copy number which was reversed by the methanolic extract administration. These findings suggest that the methanolic extract could be a potent neuropharmacological agent against dementia via modulating cholinergic activity, increasing of BDNF levels and promoting antioxidant action in the rat hippocampus.