Bae Dong Jung

Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration

Accumulated evidence has indicated that neuroinflammation is one of the important etiologic factors of Parkinsons disease (PD). Earlier studies have employed the inflammogen lipopolysaccharide (LPS) to induce inflammation of dopaminergic neurons. Methamphetamine (MA) dopaminergic toxicity similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity is frequently cited as a model of PD. In the present study, we examined whether striatal LPS exposure potentiates MA-induced dopaminergic toxicity. Combined treatment with LPS and MA significantly potentiates behavioral impairment and dopaminergic deficit. However, this combination did not significantly alter the other monoaminergic systems (e.g., serotonin, norepinephrine, and histamine). Consistently, microglial activation, labeled by F4/80 or Iba-1 in the nigrostriatal region was more pronounced with the combined treatment of LPS and MA compared to either treatment alone, but this combination did not significantly alter the microglial activation in other brain regions (e.g., hippocampus, dorsal raphe nuclei, and locus ceruleus). Furthermore, neuroinflammation, oxidative stress, and pro-apoptotic changes in the striatum were more accentuated with combined treatment of LPS and MA compared to either treatment alone. In addition, it is important that cytoplasmic accumulation of alpha-synuclein was observed in the substantia nigra of mice treated with LPS plus MA, and that L-Dopa treatment significantly attenuated behavioral changes and dopaminergic deficits induced by LPS plus MA. These results suggest that combined treatment of LPS with MA is a potential animal model for PD.

Antioxidant propolis attenuates kainate-induced neurotoxicity via adenosine A1 receptor modulation in the rat

We examined the effects of the antioxidant propolis on seizures induced by kainic acid (KA). Sprague-Dawley rats received propolis (75 and 150 mg/kg, p.o.) five times at 12 h intervals. KA (10 mg/kg, i.p.) was injected 1 h after the last propolis treatment. Pretreatment with propolis significantly attenuated KA-induced seizures and KA-induced increases in hippocampal AP-1 DNA binding activity in a dose-dependent manner. KA induced increases in the levels of malondialdehyde and protein carbonyl, and a decrease in the ratio of GSH/GSSG. These oxidative stresses and neuronal degenerations were significantly attenuated by pretreatment with propolis. The neuroprotective effects of propolis appeared to be counteracted by adenosine receptor antagonists [A1 antagonist, 8-cyclopentyl-1,3-dimethylxanthine (25 or 50 microg/kg); A2A antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (0.5 or 1 mg/kg); and A2B antagonist, alloxazine (1.5 or 3.0 mg/kg)]. However, this counteraction was most pronounced in the presence of the A1 antagonist. Our results suggest that the protective effect of propolis against KA-induced neurotoxic oxidative damage is, at least in part, via adenosine A1 receptor modulation.

Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration.

Platelet-activating factor (PAF), a potent mediator of inflammatory and immune responses, plays various roles in neuronal functions. However, little is known about the role of PAF/platelet-activating factor receptor (PAF-R) in Parkinsons disease. Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in significant increases in PAF species in the striatum of wild-type mice. These increases paralleled PAF-R gene expression in wild-type mice. Although nuclear factor kappa B (NF-κB) DNA-binding activity was increased significantly in MPTP-treated wild-type mice, this increase was not significant in PAF-R antagonist ginkgolide B (GB)-treated mice or PAF-R knockout (PAF-R(-/-)) mice. Pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, significantly ameliorated the dopaminergic deficits induced by MPTP in wild-type mice. MPTP treatment significantly increased oxidative damage, the immunoreactivity of ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglial cells, and microglial differentiation of the M1 type in the striatum of wild-type mice. Consistently, PDTC significantly attenuated MPTP-induced behavioral impairments in wild-type mice. However, dopaminergic deficits, oxidative damage, reactive microglial cells, and behavioral impairments induced by MPTP were not significantly observed in GB-treated mice or PAF-R(-/-) mice. PDTC did not significantly alter the attenuations evident in MPTP-treated PAF-R(-/-) mice, indicating that NF-κB is a critical target for neurotoxic modulation of PAF-R. We propose for the first time that PAF/PAF-R can mediate dopaminergic degeneration via an NF-κB-dependent signaling process.

PROTECTION AGAINST KAINATE NEUROTOXICITY BY PYRROLIDINE DITHIOCARBAMATE

1. The effect of pyrrolidine dithiocarbamate (PDTC) on kainate (KA)‐induced neurotoxicity was examined in Sprague‐Dawley rats.

Native plants ( Phellodendron amurense and Humulus japonicus ) extracts act as antioxidants to support developmental competence of bovine blastocysts

Objective Phellodendron amurense (P. amurense) and Humulus japonicus (H. japonicus) are closely involved in anti-oxidative response and increasing antioxidant enzymes activities. However, the effects of their extracts on development of preimplantation bovine embryos have not been investigated. Therefore, we investigated the effects of P. amurense and H. japonicus extracts on developmental competence and quality of preimplantation bovine embryos. Methods After in vitro fertilization, bovine embryos were cultured for 7 days in Charles Rosenkrans amino acid medium supplemented with P. amurense (0.01 μg/mL) and H. japonicus (0.01 μg/mL). The effect of this supplementation during in vitro culture on development competence and antioxidant was investigated. Results We observed that the blastocysts rate was significantly increased (p<0.05) in P. amurense (28.9%±2.9%), H. japonicus (30.9%±1.5%), and a mixture of P. amurense and H. japonicus (34.8%± 2.1%) treated groups compared with the control group (25.4%±1.6%). We next confirmed that the intracellular levels of reactive oxygen species (ROS) were significantly decreased (p<0.01) in P. amurense and/or H. japonicus extract treated groups when compared with the control group. Our results also showed that expression of cleaved caspase-3 and apoptotic cells of blastocysts were significantly decreased (p<0.05) in bovine blastocysts derived from both P. amurense and H. japonicus extract treated embryos. Conclusion These results suggest that proper treatment with P. amurense and H. japonicus extracts in the development of preimplantation bovine embryos improves the quality of blastocysts, which may be related to the reduction of ROS level and apoptosis.

Gingko biloba Extract Ameliorates Colonic Inflammation in DSS-induced Model of Colitis in Mice

Ulcerative colitis (UC) is a serious gastrointestinal tract disease characterized by recurrent chronic inflammation and mucosal damage of the gastrointestinal tract. The conventional therapies of choice are anti-inflammatory agents, steroids and anti-TNF-α therapy. However, inherent limitations in these therapies have steered many UC patients to supplement existing therapies with alternative medicinal products. In the current study, we tested the efficacy of Gingko bilola extract (EGb 761) in abating colonic inflammation in a DSS-induced murine model of colitis. C57BL/6 mice were administered 2% DSS in the drinking water for 7 days, then regular water for 7 days, and then 2% DSS for an additional 7 days. EGb 761 (1 mg/dose) was oral gavaged daily for the duration of the experiment. At the termination of the experiment, mice treated with EGb+DSS showed higher body weight, lower spleen weight and longer colon length compared to mice treated with DSS alone. HE-stained colon tissues also exhibited less histologic inflammation in mice treated with EGb+ DSS mice compared to mice treated with DSS alone. The serum levels inflammatory cytokines, KC and TNF-α, were also decreased in mice treated with EGb+DSS compared to mice treated with DSS alone. Finally, addition of EGb 761 to TNF-α treated colonic cell line (HT29/c1) decreased secretion of IL-8 in vitro. These results collectively suggest that EGb 761 abates induction of colitis in DSS-induced model of colitis in mice.

Anti-inflammatory Effects of the Natural Compounds Cortex Phellodendri and Humulus japonicus on Pelvic Inflammatory Disease in Mice

Pelvic inflammatory disease (PID) is an inflammatory and/or infectious disorder of the upper female genital tract, including the uterus, fallopian tubes, and adjacent pelvic structures, that may spread upward to the peritoneum. Currently available treatment options have presented to produce adverse effects of various degrees, such as increased antimicrobial resistance and a limited effective duration of hormones. In the study, the Cortex Phellodendri (CP) and Humulus japonicus (HJ) among natural compounds that are believed to present biological activities with fewer side effects were tested in a PID animal model. The results suggested that the administration CP and HJ reduced clinical signs, inflammatory cytokine expression as well as secretion in uterine tissue, and neutrophil infiltration into the tissue.