• Biomolecules & Therapeutics
• /
• v.11 no.4
• /
• pp.214-223
• /
• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• Journal of Environmental Health Sciences
• /
• v.47 no.5
• /
• pp.446-453
• /
• 2021

Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

• Journal of the Korean neurological association
• /
• v.36 no.4
• /
• pp.354-357
• /
• 2018

Transient isoniazid-induced brain lesions have rarely been reported. The lesions were in the dentate nucleus of cerebellum and thalamus. Meanwhile, the neurotoxicity of rifampin has not been reported evidently. We observed bilateral lesions in the internal capsule in a young woman after taking a combination of isoniazid and rifampin. She transiently suffered numbness in both hands, dysarthria, and left side motor weakness while taking the medication. Isoniazid may induce structural lesions in various brain areas including the internal capsule.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.2
• /
• pp.217-225
• /
• 2021

This study aimed to investigate the neuroprotective effects of 1-methoxylespeflorin G11 (MLG), a pterocarpan, against glutamate-induced neurotoxicity in neuronal HT22 hippocampal cells. The protective effects of MLG were evaluated using MTT assay and microscopic analysis. The extent of apoptosis was studied using flow cytometric analysis performed on the damaged cells probed with annexin V/propidium iodide. Moreover, mitochondrial reactive oxygen species (ROS) were assessed using flow cytometry through MitoSOXTM Red staining. To determine mitochondrial membrane potential, staining with tetramethylrhodamine and JC-1 was performed followed by flow cytometry. The results demonstrated that MLG attenuates glutamate-induced apoptosis in HT22 cells by inhibiting intracellular ROS generation and mitochondrial dysfunction. Additionally, MLG prevented glutamate-induced apoptotic pathway in HT22 cells through upregulation of Bcl-2 and downregulation of cleaved PARP-1, AIF, and phosphorylated MAPK cascades. In addition, MLG treatment induced HO-1 expression in HT22 cells. These results suggested that MLG exhibits neuroprotective effects against glutamate-induced neurotoxicity in neuronal HT22 cells by inhibiting oxidative stress and apoptosis.

• Journal of Interdisciplinary Genomics
• /
• v.5 no.2
• /
• pp.35-41
• /
• 2023

Background: Ca²⁺ signaling plays a vital role in neuronal signaling and altered Ca²⁺ homeostasis in Parkinson's disease (PD). Overexpression of αSYN significantly promote the Ca²⁺-Calmodulin (CaM) activity and subsequent nuclear translocation of nuclear factor of activated T cells (NFAT) transcription factor in dopaminergic neurons of midbrain. However, the exact role of Ca²⁺-CaM and NFAT in PD pathology is yet to be elucidated. Methods: We designed the CaM-NFAT-oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for NFAT transcription factor and CaM mRNA. Then, the effect of CaM-NFAT-ODN on 1-methyl-4-phenylpyridinium (MPP⁺)-mediated neurotoxicity was investigated in mimic PD model in vitro. Results: First, the expression of αSYN and CaM was strongly increased in substantia nigra (SN) of PD and the expression of tyrosine hydroxylase (TH) was strongly increased in control SN. Additionally, the expression of apoptosis marker proteins was strongly increased in SN of PD. Transfection of CaM-NFAT-ODN repressed CaM and pNFAT, the target genes of this ODN in rat embryo primary mesencephalic neurons. It also reduced ERK phosphorylation, a downstream target of these genes. These results demonstrated that CaM-NFAT-ODN operated successfully in rat embryo primary mesencephalic neurons. Transfection of CaM-NFAT-ODN repressed TH reduction, αSYN accumulation, and apoptosis by MPP⁺-induced neurotoxicity response through Ca²⁺ signaling and mitogen-activated protein kinases (MAPK) signaling. Conclusion: Synthetic CaM-NFAT-ODN has substantial therapeutic feasibility for the treatment of neurodegenerative diseases.

• Journal of Preventive Medicine and Public Health
• /
• v.25 no.1 s.37
• /
• pp.13-25
• /
• 1992

This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular $Ca^{2+}$concentration of the neuron. Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride($25{\mu}M,\;50{\mu}M,\;100{\mu}M$) and sodium selenite($200{\mu}M$) on free intrasynaptosomal $Ca^{2+}$ concentration were studied using the fluorescent $Ca^{2+}$ indicator fura -2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succlnic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular $Ca^{2+}$ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal $Ca^{2+}$ concentration were measured with fura-2 in vitro. The results were summarized as follows ; 1. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of $CH_3HgCl$ only. 2. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of $CH_3HgCl$ only. Particularly pretreatment of $Na_2SeO_3$ significantly more compared to the administration of $CH_3HgCl$ only. The concentration of adenosine-5'-triphosphate in $Na_2SeO_3$ treatment groups revealed a favourable effect compared to the administration of $CH_3HgCl$ only. 3. Intracellular $Ca^{2+}$ concentration in administration of $CH_3HgCl$ only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time interval more decreased significantly intracellular $Ca^{2+}$ concentration compared to the administration of $CH_3HgCl$ only. 4. Free intrasynaptosomal $Ca^{2+}$ concentration in the combined administration of $CH_3HgCl$ and $Na_2SeO_3$ was decreased ($24%{\sim}40%$) significantly more than the administration of $CH_3HgCl$ only. From the above results, the specific dosage of $Na_2SeO_3$ decreased increment of intracellular $Ca^{2+}$ concentration induced by administration of $CH_3HgCl$. These findings suggest the protective mechanism of $Na_2SeO_3$ on the neurotoxicity of $CH_3HgCl$.

• Natural Product Sciences
• /
• v.13 no.3
• /
• pp.268-271
• /
• 2007

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Bioassay-guided fractionation of the MeOH extract of the seeds of Alpinia katsumadai Hayata (Zingiberaceae) furnished three phenolic compounds, alpinetin (1), pinocembrin (2), and (+)-catechin (3). Compounds 2 and 3 showed the potent neuroprotective effects on glutamate-induced neurotoxicity and reactive oxygen species (ROS) generation in the mouse hippocampal HT22 cells. In addition, Compounds 2 and 3 showed significant DPPH free radical scavenging effect. These results suggest that compounds 2 and 3 could be the effective candidates for the treatment of ROS-related neurological diseases.

• Toxicological Research
• /
• v.16 no.2
• /
• pp.133-139
• /
• 2000

This study was designed to evaluate the mechanism by which reactive nitrogen intermediates (RNI) induced the cytotoxicity of human doparminergic neuroblastoma SH-SY5Y cells. 3-Morpholino-sydnonimine (SIN-l), a donor of peroxynitrite (ONOO) and sodium nitroprusside (SNP), a donor of nitric oxide (NO) induced cell detachment and apoptotic death, as characterized by chromatin condensation, the ladder pattern fragmentation of genomic DNA and morphological nuclear changes. SIN-l also induced the activation of caspase 3-like protease in a time-dependent manner. Exogenous antioxidants, such as reduced glutathione (GSH), N-acetylcysteine (NAC), and selenium protected the cells from apoptotic death and reduced the activation of caspase 3-like protease by SIN-1. Furthermore, SIN-l directly reduced the intracellular levels of glutathione. Taken together, these data suggested that RNI including NO and peroxynitrite decrease the concentration of intracellular antioxidant such as GSH, which lead to the apoptotic death of human neuroblastoma SH-SY5Y cells.

• The Korean Journal of Physiology
• /
• v.30 no.2
• /
• pp.289-297
• /
• 1996

Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.

• YAKHAK HOEJI
• /
• v.39 no.4
• /
• pp.450-460
• /
• 1995

The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.