Search results for "neurotoxicity"
showing 10 items of 105 documents
Efavirenz alters mitochondrial respiratory function in cultured neuron and glial cell lines.
2015
Abstract Background The NNRTI efavirenz is among the most widely employed antiretroviral drugs. Although it is considered safe, efavirenz has been linked with several adverse effects including neurological manifestations, which appear in the majority of the patients on efavirenz-containing regimens. The molecular mechanisms responsible for these manifestations are not understood, but mounting evidence points to altered brain bioenergetics. Methods We evaluated the effect of short-term efavirenz treatment on the mitochondrial respiratory function of cultured glioblastoma and differentiated neuroblastoma cell lines using a Seahorse Extracellular Flux Analyzer. Results Incubation with efaviren…
Efavirenz and the CNS: what we already know and questions that need to be answered
2015
The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of conc…
Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1
2015
One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated re…
Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase.
2006
The pathogenetic processes underlying the selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) are complex and still not completely understood even in the cases of inherited disease caused by mutations in the Cu/Zn superoxide dismutase-dependent (SOD1) gene. Recent evidence supports the view that ALS is not a cell-autonomous disease and that glial-neuron cross-talk, throughout cytokines and other toxic factors like the nitric oxide and superoxide, is a crucial determinant for the induction of motor neuron death. This cell-cell interaction may determine the progression of the disease through processes that are likely independent of the initial trigger and that may conve…
Beta-amyloid monomers are neuroprotective
2009
The 42-aa-long β-amyloid protein—Aβ1-42—is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Aβ peptides (Lambert et al., 1998) indicate that self-association of Aβ1-42monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42is unknown. The evidence that Aβ1-42is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42monomers support …
Gender differences in the neurotoxicity of metals in children
2013
Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on…
[15] Glutathione and protein kinase C in peripheral nervous tissue
1995
Publisher Summary This chapter focuses on the Glutathione and Protein Kinase C (PKC) in peripheral nervous tissue. It has long been known that the redox state of thiols in peripheral neural structures might play an important role in electrophysiological function. Former studies suggested that the integrity of certain sulfhydryl groups in nerve fibers would be essential for conduction. This classic work showed data strongly suggesting that the blockade of SH groups resulted in a loss of excitability and a reduction of the resting potential, and proposed for the first time the role of SH groups in the relationship between structure and function in nerve. The histochemical localization of glut…
Novel approaches in diagnosis and therapy of Creutzfeldt-Jakob disease.
2000
The scrapie prion protein, PrP(Sc), as well as its peptide fragment, PrP106-126, are toxic on neuronal cells, resulting in cell death by an apoptotic, rather than necrotic mechanism. The apoptotic process of neuronal cells induced by prion protein supports diagnosis and offers potential targets for therapeutic intervention of the prion diseases. Among the cerebrospinal fluid (CSF) proteins, which may serve as markers of neuronal cell death associated with prion diseases, the 14-3-3 protein(s) turned out to be the most promising one. A new sensitive assay allows the detection of even small changes in the normally low levels of these proteins. In vitro, the toxic effects displayed by PrP(Sc) …
General anaesthetics and the developing brain: an overview
2014
Various experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. To gain more insight into possible neurotoxic effects on the human brain of infants and small children, a number of retrospective studies have been performed. At present, there is no clear evidence that exposure to anaesthesia up to …
Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.
2013
This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate…