• Toxicological Research
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• v.20 no.3
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• pp.241-250
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• 2004

We previously found that bisphenol A (BPA) caused neurotoxic behavioral alteration. Since disturbance of calcium homeostasis is an implicated contributor in the neurotoxic mechanism of environmental toxicants, we investigated whether BPA alters calcium homeostasis. Unlike other neurotoxic agents which cause increase of intracellular calcium level, BPA decreased $[Ca^{2+}]_i$ dose-dependently in PC12 cells and cortical neuronal cells regardless of the calcium existence in buffer. BPA at greater concentrations than 100 $\mu\textrm{M}$ reduced cell viability significantly in both types of cells. BPA also suppressed L-glutamate (L-type channel activator, 30 mM) and trifluoperazine (calmodulin antagonist, 30 $\mu\textrm{M}$)-induced increase of $[Ca^{2+}]_i$. BPA further lowered caffeine (RYR activator, 100 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$, but did not alter dantrolene (RYR inhibitor, 100 $\mu\textrm{M}$), heparin (IP3 inhibitor, 200 units/ml) and xestospongin C (IP3 inhibitor, 5 $\mu\textrm{M}$)-decreased $[Ca^{2+}]_i$. Cell viability was not directly related to intracellular calcium change by bisphenol A that alternation of intracellular calcium may not be a direct causal factor of BPA-induced neuronal cell death.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.2
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• pp.55-61
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• 2020

During dental treatment, a dentist usually applies the local anesthesia. Therefore, all dentists should have expertise in local anesthesia and anesthetics. Local anesthetics have a neurotoxic effect at clinically relevant concentrations. Many studies have investigated the mechanism of neurotoxicity of local anesthetics but the precise mechanism of local anesthetic-induced neurotoxicity is still unclear. In addition, it is difficult to demonstrate the direct neurotoxic effect of local anesthetics because perioperative nerve damage is influenced by various factors, such as the anesthetic, the patient, and surgical risk factors. This review summarizes knowledge about the pharmacology of local anesthetics, nerve anatomy, and the incidence, risk factors, and possible cellular mechanisms of local anesthetic-induced neurotoxicity.

• Toxicological Research
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• v.28 no.2
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• pp.107-112
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• 2012

Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental pollutants. Recently, it is suggested that neurotoxic effects such as motor dysfunction and impairment in memory and learning have been associated with PCB exposure. However, structure relationship of PCB congeners with neurotoxic effects remains unknown. Since PKC signaling pathway is implicated in the modulation of motor behavior as well as learning and memory and the role of PKC are subspecies-specific, we attempted to study the effects of structurally distinct PCBs on the total PKC activity as well as subspecies of PKC in cerebellar granule cell culture model. Cells were exposed to 0, 25 and 50 ${\mu}M$ of PCB-126, PCB-169, PCB-114, PCB-157, PCB-52 and PCB-4 for 15 min. Cells were subsequently analyzed by [$^3H$] phorbol ester binding assay or immunoblotted against PKC-${\alpha}$ and -${\varepsilon}$ monoclonal antibodies. While non-dioxin-like-PCB (PCB-52 and PCB-4) induced a translocation of PKC-${\alpha}$ and -${\varepsilon}$ from cytosol to membrane fraction, dioxin-like PCBs (PCB-126, -169, -114, -157) had no effects. [$^3H$] Phorbol ester binding assay also revealed structure-dependent increase similar to translocation of PKC isozymes. While PCB-4 induced translocation of PKC-${\alpha}$ and -${\varepsilon}$ was inhibited by ROS inhibitor, the pattern of translocation was not affected in presence of AhR inhibitor. It is suggested that PCB-4-induced PKC activity may not be mediated via AhR-dependent pathway. Taken together, our findings suggest that chlorination of ortho-position in PCB may be a critical structural moiety associated with neurotoxic effects, which may be preferentially mediated via non-AhR-dependent pathway. Therefore, the present study may contribute to understanding the neurotoxic mechanism of PCBs as well as providing a basis for establishing a better neurotoxic assessment.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.130-130
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.111-111
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• 2004

• Molecular & Cellular Toxicology
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• v.4 no.2
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• pp.164-169
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• 2008

Methylmercury (MeHg) is known to have devastating effects on the mammalian nervous system. In order to characterize the mechanism of MeHg-induced neurotoxicity, we investigated the analysis of transcriptional profiles on human 8k cDNA microarray by treatment of $1.4{\mu}M$ MeHg at 3, 12, 24 and 48h in human neuroblastoma SH-SY5Y cell line. Some of the identified genes by MeHg treatment were significant at early time points (3h), while that of others was at late time points (48h). The early response genes that may represent those involved directly in the MeHg response included pantothenate kinase 3, a kinase (PRKA) anchor protein (yotiao) 9, neurotrophic tyrosine kinase, receptor, type 2 gene, associated with NMDA receptor activity regulation or perturbations of central nervous system homeostasis. Also, when SH-SY5Y cells were subjected to a longer exposure (48h), a relative increase was noted in a gene, glutamine-fructose-6-phosphate transaminase 1, reported that overexpression of this gene may lead to the increased resistance to MeHg. To confirm the alteration of these genes in cultured neurons, we then applied real time-RT PCR with SYBR green. Thus, this result suggests that a neurotoxic effect of the MeHg might be ascribed that MeHg alters neuronal receptor regulation or homeostasis of neuronal cells in the early phase. However, in the late phase, it protects cells from neurotoxic effects of MeHg.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.399-409
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• 2021

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.130-130
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• 2003

Methylmercury (MeHg) is a well-known neurotoxicant that causes severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far.(omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.4
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• pp.149-154
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• 2007

Kainic acid (KA) causes neurodegeneration, but no consensus has been reached concerning its mechanism. Nitric oxide may be a regulator of the mechanism. We identified differentially expressed genes in the hippocampus of mice treated with kainic acid, together with or without L-NAME, a nonselective nitric oxide synthase inhibitor, using a new differential display PCR method based on annealing control primers. Eight genes were identified, including clathrin light polypeptide, TATA element modulatory factor 1, neurexin III, ND4, ATPase, $H^+$ transporting, V1 subunit E isoform 1, and N-myc downstream regulated gene 2. Although the functions of these genes and their products remain to be determined, their identification provides insight into the molecular mechanism(s) involved in KA-induced neuronal cell death in the hippocampal CA3 area.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.91-95
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• 2010

Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid (A${\beta}$) peptides. It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have affects on the mechanism of memory formation, which are generated by processing of amyloid precursor protein (APP). In this study, effects of Styrax Liquides (SL) on the metabolism of APP were analyzed. SL inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing a mutation of APPswe. Immunoblotting study showed that it inhibited ${\beta}$-site APP cleaving enzyme (BACE) from the APPswe cells. We suggest that SL inhibits APP metabolism and A${\beta}$ generation by the means of BACE inhibitory mechanism. This is the first report that SL inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.