Neurotoxicity Research

Oxygen (O2 ) supplementation is commonly used to treat hypoxia in patients with respiratory failure. However, indiscriminate use can lead to hyperoxia, a condition detrimental to living tissues, particularly the brain. The brain is sensitive to reactive oxygen species (ROS) and inflammation caused by high concentrations of O2 , which can result in brain damage and mitochondrial dysfunction, common features of neurodegenerative disorders. Hyperoxia leads to increased production of ROS, causing oxidative stress, an imbalance between oxidants and antioxidants, which can damage tissues...

The investigation into the hippocampal function and its response to heavy metal exposure is crucial for understanding the mechanisms underlying neurotoxicity, this can potentially inform strategies for mitigating the adverse effects associated with heavy metal exposure. Melatonin is an essential neuromodulator known for its efficacy as an antioxidant. In this study, we aimed to determine whether melatonin could protect against Nickel (Ni) neurotoxicity. To achieve this, we performed an intracerebral injection of Ni (300 µM NiCl2 ) into the right hippocampus of male Wistar rats, followed by melatonin treatment...

Alzheimer's disease (AD) involves a neurodegenerative process that has not yet been prevented, reversed, or stopped. Continuing with the search for natural pharmacological treatments, flavonoids are a family of compounds with proven neuroprotective effects and multi-targeting behavior. The American genus Dalea L. (Fabaceae) is an important source of bioactive flavonoids. In this opportunity, we tested the neuroprotective potential of three prenylated flavanones isolated from Dalea species in a new in vitro pre-clinical AD model previously developed by us...

Chronic cerebral hypoperfusion (CCH) is a primary contributor to cognitive decline in the elderly. Enriched environment (EE) is proved to improve cognitive function. However, mechanisms involved remain unclear. The purpose of the study was exploring the mechanisms of EE in alleviating cognitive deficit in rats with CCH. To create a rat model of CCH, 2-vessel occlusion (2-VO) surgery was performed. All rats lived in standard or enriched environments for 4 weeks. Cognitive function was assessed using the novel object recognition test and Morris water maze test...

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, β-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe)...

Glutamate is the major excitatory amino acid in the vertebrate brain, playing an important role in most brain functions. It exerts its activity through plasma membrane receptors and transporters, expressed both in neurons and glia cells. Overstimulation of neuronal glutamate receptors is linked to cell death in a process known as excitotoxicity, that is prevented by the efficient removal of the neurotransmitter through glutamate transporters enriched in the glia plasma membrane and in the components of the blood-brain barrier (BBB)...

Maternal hyperhomocysteinemia (HCY) induced by genetic defects in methionine cycle enzymes or vitamin imbalance is known to be a pathologic factor that can impair embryonal brain development and cause long-term consequences in the postnatal brain development as well as changes in the expression of neuronal genes. Studies of the gene expression on this model requires the selection of optimal housekeeping genes. This work aimed to analyze the expression stability of housekeeping genes in offspring brain. Pregnant female Wistar rats were treated daily with a 0...

Neurodegenerative disorders are chronic brain diseases that affect humans worldwide. Although many different factors are thought to be involved in the pathogenesis of these disorders, alterations in several key elements such as the ubiquitin-proteasome system (UPS), the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and the endocannabinoid system (ECS or endocannabinoidome) have been implicated in their etiology. Impairment of these elements has been linked to the origin and progression of neurodegenerative disorders, while their potentiation is thought to promote neuronal survival and overall neuroprotection, as proved with several experimental models...

Traumatic brain injury (TBI) is one of the important risk factors for the development of Alzheimer's disease (AD). However, the molecular mechanism by which TBI promotes the progression of AD is not elucidated. In this study, we showed that the abnormal production of E2F1 is a major factor in promoting the neuropathological and cognitive deterioration of AD post-TBI. We found that repeated mild TBI can aggravate the neuropathology of AD in APP/PS1 mice. At the same time, the co-expression of E2F1 and beta-site APP cleaving enzyme 1 (BACE1) was upregulated when the mouse hippocampus was dissected...

Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking...

Cerebral ischemic stroke (CIS) is the main cause of disability. METTL3 is implicated in CIS, and we explored its specific mechanism. Middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cell model were established and treated with LV-METTL3 or DAA, oe-METTL3, miR-335-3p mimics, or DAA, to assess their effects on MCAO rat neurological and motor function, cerebral infarction area, brain water content, microglial activation, blood-brain barrier (BBB) permeability, and NLRP3 inflammasome activation...

Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM)...

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2 ] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia...

The permeability of the blood-brain barrier (BBB) is increased in Alzheimer's disease (AD). This plays a key role in the instigation and maintenance of chronic inflammation during AD. Experiments using AD models showed that the increased permeability of the BBB was mainly caused by the decreased expression of tight junction-related proteins occludin and claudin-5. In this study, we found that ZNF787 and HDAC1 were upregulated in β-amyloid (Aβ)1-42 -incubated endothelial cells, resulting in increased BBB permeability...

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, the first being Alzheimer's disease. Patients with PD have a loss of dopaminergic neurons in the substantia nigra of the basal ganglia, which controls voluntary movements, causing a motor impairment as a result of dopaminergic signaling impairment. Studies have shown that mutations in several genes, such as SNCA, PARK2, PINK1, DJ-1, ATP13A2, and LRRK2, and the exposure to neurotoxic agents can potentially increase the chances of PD development...

Therapy-Induced Senescence (TIS) is a form of senescence that is typically described in malignant cells in response to the exposure of cancer chemotherapy or radiation but can also be precipitated in non-malignant cells. TIS has been shown to contribute to the development of several cancer therapy-related adverse effects; however, evidence on its role in mediating chemotherapy-induced neurotoxicity, such as Chemotherapy-induced Peripheral Neuropathy (CIPN), is limited. We here show that cisplatin treatment over two cycles (cumulative dose of 23 mg/kg) provoked mechanical allodynia and thermal hyperalgesia in Sprague-Dawley rats...

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of neuronal function and structure. While several genetic and environmental factors have been implicated in the pathogenesis of these disorders, emerging evidence suggests that transposable elements (TEs), once considered "junk DNA," play a significant role in their development and progression. TEs are mobile genetic elements capable of moving within the genome, and their dysregulation has been associated with genomic instability, altered gene expression, and neuroinflammation...

Chemotherapy-induced neuropathic pain (CIPN) is a common side effect of antitumor chemotherapeutic agents. It describes a pathological state of pain related to the cumulative dosage of the drug, significantly limiting the efficacy of antitumor treatment. Sofas strategies alleviating CIPN still lack. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in many pathologic pains. In this study, we explored the effects of CGRP blocking on CIPN and potential mechanisms. Total dose of 20.7 mg/kg cisplatin was used to establish a CIPN mouse model...

Rattus norvegicus is the second most used laboratory species and the most widely used model in neuroscience. Nonetheless, there is still no agreement regarding the temporal relationship of development between humans and rats. We addressed this question by examining the time required to reach a set of homologous developmental milestones in both species. With this purpose, a database was generated with data collected through a bibliographic survey. This database was in turn compared with other databases about the same topic present in the literature...

Asprosin, a hormone secreted from adipose tissue, has been implicated in the modulation of cell viability. Current studies suggest that neurological impairments are increased in individuals with obesity-linked diabetes, likely due to the presence of excess adipose tissue, but the precise molecular mechanism behind this association remains poorly understood. In this study, our hypothesis that asprosin has the potential to mitigate neuronal damage in a high glucose (HG) environment while also regulating the expression of microRNA (miRNA)-181a, which is involved in critical biological processes such as cellular survival, apoptosis, and autophagy...