Abstract:
:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from the progressive loss of motor neurons in the spinal cord and brain. To date, clinically effective neuroprotective agents have not been available. The current study demonstrates for the first time that huperzine A, a potential neuroprotective agent, has the ability to protect a motor neuron-like cell line and motor neurons in spinal cord organotypic cultures from toxin-induced cell death. The neuroblastoma-spinal motor neuron fusion cell line, NSC34 and rat spinal cord organotypic cultures (OTC) were exposed to cell death inducers for 24 h or 14 d, respectively, with and without pre-treatment with huperzine A. The inducers used here include: staurosporine, thapsigargin, hydrogen peroxide (H2O2), carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and L-(-)-threo-3-hydroxyaspartic acid (THA). These agents were selected as they induce apoptosis/necrosis via mechanisms implicated in patients with generalized motor neuron disease. Cell death was determined in NSC34 cells by metabolic activity, caspase activity/expression and by nuclear morphology and in the OTCs, using immunohistochemistry and Western blot analysis. Nuclear staining of NSC34 cells revealed cell death induced by staurosporine, thapsigargin, H2O2 and CCCP. This induction was significantly reduced with 2 h pre-treatment with 10 microM huperzine A (maximum, 35% rescue; p 0.05) following exposure to staurosporine, thapsigargin and H2O2 but not with CCCP. These data were supported by the metabolic assays and caspase activity. In addition, pre-treatment with huperzine A dramatically improved motor neuron survival, based on choline acetyltransferase (ChAT) expression analysis in OTCs following exposure to THA, and compared to THA-treated control cultures. These studies are currently being extended to include other inducers and with additional compounds as potential drug therapies that could be used in combination for the treatment of patients with ALS.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Hemendinger RA,Armstrong EJ 3rd,Persinski R,Todd J,Mougeot JL,Volvovitz F,Rosenfeld Jdoi
10.1007/BF03033367subject
Has Abstractpub_date
2008-01-01 00:00:00pages
49-61issue
1eissn
1029-8428issn
1476-3524journal_volume
13pub_type
杂志文章abstract::The level of acetylcholine, a neurotransmitter essential for processing memory and learning, is lower in the brains of patients with Alzheimer's disease due to the higher concentration of the enzyme acetylcholinesterase. The main compounds used for Alzheimer's treatment are acetylcholinesterase inhibitors. Quercetin c...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00142-7
更新日期:2020-04-01 00:00:00
abstract::High-level occupational exposure to volatile organic solvents may elicit neurotoxic effects, especially on central and peripheral structures involved in balance ability. Studies on balance control in relation with exposure levels close to the threshold limit values are scarce. This study aimed to assess the neurotoxic...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9018-0
更新日期:2009-02-01 00:00:00
abstract::Organophosphate (OP) poisoning is associated with long-lasting neurological damage, which is attributed mainly to the excessive levels of glutamate caused by the intoxication. Glutamate toxicity, however, is not specific to OP poisoning, and is linked to propagation of damage in both acute and chronic neurodegenerativ...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-013-9388-1
更新日期:2013-08-01 00:00:00
abstract::Reoccurring seasonal cyanobacterial harmful algal blooms (CHABs) persist in many waters, and recent work has shown links between CHAB and elevated risk of amyotrophic lateral sclerosis (ALS). Quantifying the exposure levels of CHAB as a potential risk factor for ALS is complicated by human mobility, potential pathways...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-017-9740-y
更新日期:2018-01-01 00:00:00
abstract::Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson's disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depres...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-018-9912-4
更新日期:2018-11-01 00:00:00
abstract::Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophr...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033357
更新日期:2006-12-01 00:00:00
abstract::Neurotransmitters and neuromodulators are essential for normal nervous system development. Disturbances in the expression timetable or intensity of neurotransmitter signalling during critical periods of brain development can lead to permanent damage. Neuroactive drugs and environmental toxins interfere with neurotrans...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033568
更新日期:2007-04-01 00:00:00
abstract::Maillard reactions have been explored by food chemists for many years. It is only recently that the advanced glycation end products (AGEs), the end products of the Maillard reaction, have been detected in a wide variety of diseases such as diabetes, atherosclerosis, cataractogenesis, Parkinson disease and Alzheimer di...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/1029840290007321
更新日期:2002-05-01 00:00:00
abstract::The aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-013-9403-6
更新日期:2013-10-01 00:00:00
abstract::GSK3beta is prominent for its role in apoptosis signaling and has been shown to be involved in Parkinson's disease (PD) pathogenesis. The overall effects of GSK3beta activity on cell fate are well-established, but the effects of mitochondrial GSK3beta activity on mitochondrial function and cell fate are unknown. Here ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033861
更新日期:2008-12-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disorder that is hallmarked by pathological changes associated with the death of dopaminergic neurons, particularly in the extrapyramidal system (substantia nigra pars compacta, striatum) of the brain. Although the causes of slow neuronal death in PD are unknown, both ge...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9556-6
更新日期:2016-04-01 00:00:00
abstract::The original version of this article contained mistakes, and the authors would like to correct them. Some parts of the image in Figure 5 were missing. The correct Figure 5 is shown at the next page. ...
journal_title:Neurotoxicity research
pub_type: 已发布勘误
doi:10.1007/s12640-018-9982-3
更新日期:2019-05-01 00:00:00
abstract::Benzophenone-3 (BP-3), the most widely used UV chemical filter, is absorbed well through the skin and gastrointestinal tract and can affect some body functions, including the survival of nerve cells. Previously, we showed that BP-3 evoked a neurotoxic effect in male rats, but since the effects of this compound are kno...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00163-7
更新日期:2020-03-01 00:00:00
abstract::U373MG cells are able to take up aminochrome that induces glutathione transferase M2-2 (GSTM2) expression in a concentration-dependent manner where 100 µM aminochrome increases GSTM2 expression by 2.1-fold (P < 0.001) at 3 h. The uptake of (3)H-aminochrome into U373MG cells was significantly reduced in the presence of...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-014-9500-1
更新日期:2015-04-01 00:00:00
abstract::Autism was recently associated with a urinary porphyrin pattern indicative of mercury toxicity in a large cohort of French children. The IRB of the Institute for Chronic Illnesses approved the present study. A total of 37 consecutive American patients (> or = 7 years-old) with autism spectrum disorders (ASDs) (Diagnos...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033334
更新日期:2006-08-01 00:00:00
abstract::Microglial activation and subsequent release of toxic pro-inflammatory factors are believed to play an important role in neuronal cell death associated with Parkinson's disease (PD). Compounds that inhibit microglia activation and suppress pro-inflammatory factor release have been reported to have neuroprotective effe...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9328-5
更新日期:2013-02-01 00:00:00
abstract::Methylglyoxal (MG) is a dicarbonyl molecule exhibiting high reactivity and is a major responsible for glycation in human cells. Accumulation of MG is seen in certain diseases, including metabolic disturbances and neurodegeneration. Among other effects, MG promotes mitochondrial dysfunction, leading to bioenergetic dec...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00091-1
更新日期:2019-10-01 00:00:00
abstract::Huntington's disease (HD) is a fatal autosomal dominantly inherited brain disease caused by excessively expanded CAG repeats in gene which encodes huntingtin protein. These abnormally encoded huntingtin proteins and their truncated fragments result in disruption of cellular quality mechanism ultimately triggering neur...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/s12640-019-00087-x
更新日期:2019-10-01 00:00:00
abstract::Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (-) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00134-7
更新日期:2020-02-01 00:00:00
abstract::Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of B...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-015-9526-z
更新日期:2015-05-01 00:00:00
abstract::Integrin β8 is a key regulator of vascular homeostasis in brain development and in vitro studies show that β8 protects against oxygen-glucose deprivation-induced neuronal apoptosis. However, the role β8 plays in vivo in neonatal rats with hypoxic-ischemic (HI) brain injury is not known. Here, we report the function of...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-012-9312-0
更新日期:2012-11-01 00:00:00
abstract::Deficit schizophrenia is characterized by leaky intestinal tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular, and vascular barriers in the gut and blood-brain barriers. We measured IgA responses to occludin, cla...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-019-00054-6
更新日期:2019-08-01 00:00:00
abstract::Cultured rat fibroblasts, monkey kidney tumor cells (line Vero) and murine neuroblastoma cells were exposed to dopamine or dopaminochrome in the presence and absence of ascorbic acid. Ascorbic acid is able to potentiate the toxicity of both dopamine and dopaminochrome for all the tested cells. The toxicity of dopamino...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/BF03033278
更新日期:1999-12-01 00:00:00
abstract::The isolated sciatic nerve of the frog was used to assess the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the peripheral nervous system. For each experiment, both sciatic nerves were used. The evoked compound action potentials of the nerves were monitored for over 48 h as an indication of their ...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1080/10298420290007592
更新日期:2002-02-01 00:00:00
abstract::Propofol and sevoflurane are commonly used drugs in pediatric anesthesia. Exposure of newborn rats to a variety of anesthetics has been shown to induce apoptotic neurodegeneration in the developing brain. Newborn Wistar rats were treated with repeated intraperitoneal injections of propofol or sevoflurane inhalation an...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9063-8
更新日期:2009-08-01 00:00:00
abstract::Reward-related incentive learning involves the acquisition by neutral stimuli of an enhanced ability to elicit approach and other responses. Previous studies have shown that both dopamine (DA) and glutamate (Glu) play critical roles in this type of learning. Signaling molecules are intracellular messengers that partic...
journal_title:Neurotoxicity research
pub_type: 杂志文章,评审
doi:10.1007/BF03033301
更新日期:2004-01-01 00:00:00
abstract::The expanding arsenal of transgenic mice has created a powerful tool for investigating the biological mechanisms involved in ototoxicity. However, cisplatin ototoxicity is difficult to investigate in mice because of their small size and vulnerability to death by nephrotoxicity. To overcome this problem, we developed a...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-011-9244-0
更新日期:2011-11-01 00:00:00
abstract::Several reports suggest that 3,4-methylenedioxymethamphetamine (MDMA) induces neurotoxic effects and gliosis. Since recreational use of MDMA is often associated with caffeinated beverages, we investigated whether caffeine interferes with MDMA-induced astroglia and microglia activation, thus facilitating its neurotoxic...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-009-9125-y
更新日期:2010-05-01 00:00:00
abstract::Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In the present work, we evaluated the effect of prenatal hyperhomocysteinemia on structural and ultrastructural organization, neuronal and glial cell number, apoptosis (c...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-020-00233-w
更新日期:2020-08-01 00:00:00
abstract::Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in...
journal_title:Neurotoxicity research
pub_type: 杂志文章
doi:10.1007/s12640-016-9599-3
更新日期:2016-05-01 00:00:00