Role of Glial Cells and Receptors in Schizophrenia Pathogenesis.

The specific pathogeneses of schizophrenia (SCZ) remain an enigma despite extensive research that has implicated both genetic and environmental factors. Recent revelations that dysregulated immune system caused by glial cell overactivation result in neuroinflammation, a key player in neurodegenerative as well as neuropsychiatric disorders including SCZ are providing novel clues on potential therapeutic interventions. Here, we review the roles of glial cells (Dr.

Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.

Copper (Cu) is essential for brain development and function, yet its overload induces neuronal damage and contributes to neurodegeneration and other neurological disorders. Multiple studies demonstrated that Cu neurotoxicity is associated with mitochondrial dysfunction, routinely assessed by reduction of mitochondrial membrane potential. Nonetheless, the role of alterations of mitochondrial dynamics in brain mitochondrial dysfunction induced by Cu exposure is still debatable.

Intercellular Adhesion Molecule 1 (ICAM-1): An Inflammatory Regulator with Potential Implications in Ferroptosis and Parkinson's Disease.

Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important adhesion molecules during leukocyte recruitment. It is encoded by the gene and plays a central role in inflammation. Its crucial role in many inflammatory diseases such as ulcerative colitis and rheumatoid arthritis are well established.

Effects of high-intensity chronic noise on spatial memory in male versus female rats.

The detrimental effects of high-intensity noise on the auditory system and emotional status, including the induction of anxiety, are well documented. Preclinical as well as epidemiological and clinical studies have solidly established differential responses between males and females to various stressful stimuli, including high-intensity white noise (HIWN). However, whether chronic exposure to noise affects cognitive functions and whether this effect is sex dependent has not been adequately addressed.

Ferroptosis as an emerging target in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies.

The Role of Gut Microbiota in the Neuroprotective Effects of Selenium in Alzheimer's Disease.

The objective of the present review was to provide a timely update on the molecular mechanisms underlying the beneficial role of Se in Alzheimer's disease pathogenesis, and discuss the potential role of gut microbiota modulation in this neuroprotective effect. The existing data demonstrate that selenoproteins P, M, S, R, as well as glutathione peroxidases and thioredoxin reductases are involved in regulation of Aβ formation and aggregation, tau phosphorylation and neurofibrillary tangles formation, as well as mitigate the neurotoxic effects of Aβ and phospho-tau. Correspondingly, supplementation with various forms of Se in cellular and animal models of AD was shown to reduce Aβ formation, tau phosphorylation, reverse the decline in brain antioxidant levels, inhibit neuronal oxidative stress and proinflammatory cytokine production, improve synaptic plasticity and neurogenesis, altogether resulting in improved cognitive functions.

Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.

Huntington's disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin () gene has a 50% chance of developing the disease.

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction.

Mood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions.

Iron toxicity, ferroptosis and microbiota in Parkinson's disease: Implications for novel targets.

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Iron (Fe)-dependent programmed cell death known as ferroptosis, plays a crucial role in the etiology and progression of PD. Since SNpc is particularly vulnerable to Fe toxicity, a central role for ferroptosis in the etiology and progression of PD is envisioned.

Modulation of gut microbiota with probiotics as a strategy to counteract endogenous and exogenous neurotoxicity.

The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.

Manganese in autism spectrum disorder and attention deficit hyperactivity disorder: The state of the art.

The objective of the present narrative review was to synthesize existing clinical and epidemiological findings linking manganese (Mn) exposure biomarkers to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and to discuss key pathophysiological mechanisms of neurodevelopmental disorders that may be affected by this metal. Existing epidemiological data demonstrated both direct and inverse association between Mn body burden and ASD, or lack of any relationship. In contrast, the majority of studies revealed significantly higher Mn levels in subjects with ADHD, as well as direct relationship between Mn body burden with hyperactivity and inattention scores in children, although several studies reported contradictory results.

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease.

Interactions Between the Ubiquitin-Proteasome System, Nrf2, and the Cannabinoidome as Protective Strategies to Combat Neurodegeneration: Review on Experimental Evidence.

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.

Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder.

Reciprocal communication between the gut microbiota and the brain, commonly referred to as the "gut-brain-axis" is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed.

Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-induced Toxicities in Cell Culture.

Toxic exposures to heavy metals, such as iron (Fe) and manganese (Mn), can result in long-range neurological diseases and are therefore of significant environmental and medical concerns. We have previously reported that damage to neuroblastoma-derived dopaminergic cells (SH-SY5Y) by both Fe and Mn could be prevented by pre-treatment with nicotine. Moreover, butyrate, a short chain fatty acid (SCFA) provided protection against salsolinol, a selective dopaminergic toxin, in the same cell line.

Intestinal microbiota protects against methylmercury-induced neurotoxicity.

Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32-47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity.

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and communication, manifests in early childhood and is followed by restricted and stereotyped behaviors, interests, or activities in adolescence and adulthood (DSM-V). Although genetics and environmental factors have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology.

Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases.

Toxic exposures to heavy metals, such as iron (Fe) and manganese (Mn), can result in long-range neurological diseases and are therefore of significant environmental and medical concerns. We have previously reported that damage to neuroblastoma-derived dopaminergic cells (SH-SY5Y) by both Fe and Mn could be prevented by pre-treatment with nicotine. Moreover, butyrate, a short chain fatty acid (SCFA) provided protection against salsolinol, a selective dopaminergic toxin, in the same cell line.

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles.

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms.

Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

The objective of the present study was to review the existing epidemiological and laboratory findings supporting the role of toxic metal exposure in non-alcoholic fatty liver disease (NAFLD). The existing epidemiological studies demonstrate that cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) exposure was associated both with an increased risk of NAFLD and altered biochemical markers of liver injury. Laboratory studies demonstrated that metal exposure induces hepatic lipid accumulation resulting from activation of lipogenesis and inhibition of fatty acid β-oxidation due to up-regulation of sterol regulatory element-binding protein 1 (SREBP-1), carbohydrate response element binding protein (ChREBP), peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of PPARα.

Differential effects of aging on hippocampal ultrastructure in male vs. female rats.

Age-related decline in physical and cognitive functions are facts of life that do not affect everyone to the same extent. We had reported earlier that such cognitive decline is both sex- and context-dependent. Moreover, age-associated ultrastructural changes were observed in the hippocampus of male rats.

Short- and long-term effects of chronic toluene exposure on spatial memory in adolescent and adult male Wistar rats.

Addiction to toluene-containing volatile inhalants is of significant medical and social concern, particularly among youth. These concerns are underscored by the fact that the majority of adult abusers of toluene started as teenagers. Surprisingly, however, the lasting effects of chronic toluene exposure, especially in various age groups, have not been well investigated.