Effects of 1-bromopropane on neurotrasmitter receptors, intracellular signalings and feedback inhibition in the CNS

Effects of 1-bromopropane on neurotrasmitter receptors, intracellular signalings and feedback inhibition in the CNS

S236 Abstracts / Neuroscience Research 58S (2007) S1–S244 P3-jØ8 Enhanced aggregate formation by dopamine, L-dopa, P3-j11 Cellular damages on the C...

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S236

Abstracts / Neuroscience Research 58S (2007) S1–S244

P3-jØ8 Enhanced aggregate formation by dopamine, L-dopa,

P3-j11 Cellular damages on the CNS neurons treated with

and quinone in PC12 cells

ethanol are alleviated by roasted rice bran and soybean extracts

Kazuhiro Nakaso, Satoru Ito, Yuko Yoshimoto, Keiko Imamura, Takao Takeshima, Kenji Nakashima Department of Neurology, Institute of Neurological Sciences, Tottori University, Japan

Motoko Shiozaki 1 , Naoya Hayakawa 1 , Syoichi Takeuchi 1 , Kiyotaka Wada 3 , Yasuo Uchiyama 2 , Takahiro Gotow 1 1 Lab. Cell Biol., Col. Nutr., Koshien University, Takarazuka, Japan; 2 Department Cell Biol. Neurosc., Osaka University Grad. Sch. Med., Suita, Japan; 3 Okuno Chem. Industries Co., Ltd., Osaka, Japan

The association between protein aggregation and the pathogenesis of Parkinson’s disease has been widely documented. In order to understand how Lewy bodies are formed in dopaminergic neurons, we investigated the effect of dopamine and l-dopa on the aggregate formation using neural-differentiated PC12 cells and Tet-off conditioned alpha-synuclein expressing cells. The tyrosine hydroxylase inhibitor, alpha-methyl tyrosine dramatically reduced the formation of aggregates under the proteasome-inhibited condition and upregulated proteasome activity. An in vitro aggregation assay for ubiquitin and alpha-synuclein demonstrated that dopamine and l-dopa enhanced the oligomerization of ubiquitin and alpha-synuclein, respectively. Moreover, a scavenger of quinone body cystein dramatically decreased oligomerization. These data suggest that dopamine and l-dopa enhance the formation of aggregates via quinone formation in dopaminergic neurons.

P3-jØ9 Effects of zinc by food on adjuvant arthritis in Lewis rats Masanori Kasai, Masato Shichita, Tatsuya Kozaki Department of Chemistry & BioScience, Faculty of Science, Kagoshima University, Japan We have reported that serum zinc (Zn) decrease after adjuvant arthritis (AA), however, there is no study to reveal an involvement of Zn in the expression of AA. To know whether supplement of Zn by food improve AA or did not, three types of diets, low-Zn (2.97 mg), Zn-standard (5.19 mg), Zn-sufficient (10.38 mg) diets, were used as food for male Lewis rats  received a suspension of complete Freund adjuvant (1.0 mg), injected intradermally into the tail. All AA rats showed signs of systemic inflammation after the 11th day after the inoculation. There were no significant differences in their food intakes and in their body weight changes among these groups in intact rats and also in AA rats. Hind paw volumes in AA rats of these three groups did not show any difference and it showed tendency to increase a hind paw volume according to amount of Zn including diets. Thus, the present results support our previous report that Zn is not involved in the expression of AA.

Roasted rice bran and soybean extracts have antioxidant activity to eliminate hydroxyl radical. We examined how the CNS neurons treated with 20% ethanol for 23 weeks were influenced with 1% rice bran or soybean extract in the ethanol. Immunohistochemically, expressions for neurofilament (NF) protein, antioxidant enzyme and lysosome/autophagy/apoptosis-related proteins were altered in ethanoltreated rats, but they were completely opposite in pattern with the extracts, similar in control rats drinking water alone. Immunoblottings produced results the same as those from the immunohistochemistry. Electron microscopy showed the increase in density of lipofuscin granules and axonal NFs in ethanol-treated rats, and the reduction to the normal level of such organelles with the extracts. These suggest that some components in the extracts suppress the ethanol-induced impairment in the CNS neurons.

P3-j12 Comparison research on excitatory amino acid transporters between astrocyte and microglia Jianfeng Liang, Hideyuki Takeuchi, Jun Kawanokuchi, Yoshifumi Sonobe, Yukiko Doi, Izumi Yawata, Shijie Jin, Jinyan Wang, Tetsuya Mizuno, Akio Suzumura Department of Neuroimmunology, RIEM, Nagoya University, Nagoya, Japan Glutamate-induced excitotoxicity is considered as a major cause of neurodegenerative disease. Excitatory amino acid transporters (EAATs) on glial cells are responsible for homeostasis of extracellular glutamate in the central nervous system, which may contribute to prevention of excitotoxicity. However, the difference of EAATs expression in astrocyte and microglia is not fully understood. Thus we compared EAATs expression in astrocyte and microglia. We assessed the neuroprotective function of astrocyte and microglia by neuron/astrocyte/microglia co-culture. Transcripts for EAAT1–5 were detected by RT-PCR in astrocytes, but microglia lose EAAT4 mRNA expression. Western blot analysis demonstrated that the expression of membranous EAATs in astrocytes is higher than that in microglia. The observation of co-culture system revealed that astrocyte reduce excitotoxicity. These results showed that astrocytes prevent excito-neurotoxicity via abundant EAATs. Research fund: KAKENHI (17790577).

P3-j1Ø Effects of 1-bromopropane on neurotrasmitter receptors, intracellular signalings and feedback inhibition in the CNS Yukiko Fueta, Yasuhiro Yoshida, Susumu Ueno, Toru Ishidao, Hajime Hori University of Occupational and Environmental Health, Kitakyushu, Japan 1-Bromopropane (1-BP), a new substitute for chlorofluorocarbons, could adversely affect the human nervous system. However the underlying mechanism still requires to be investigated. Here we report that 1BP potentiated GABA- but inhibited ACh-evoked responses in Xenopus oocytes expressing GABAA and nicotinic ACh receptors, respectively. 1-BP also directly enhanced recurrent inhibition in the rat hippocampus. Moreover, in cultured astrocytes, 1-BP inhibited activity of NF-␬B and expression of Bcl-xL. BDNF was also suppressed possibly through PKA pathway. Chronic inhalation disclosed hippocampal disinhibition in a concentration-dependent manner. Alteration of GABAA receptor subunit expression and reduction of BDNF and Bcl-xL expression were accompanied with the disinihibiton at 400 ppm concentration. These results clearly indicate that 1-BP has both chronic and acute neurotoxicity in the CNS. Research funds: Supported by KAKENHI (16590214, 16651027, 18510064).

P3-j13 The effect of acetylcholine receptor activation on the epileptogenesis in rat hippocampal slices Ayumi Hashimoto, Kiyohisa Natume Kyushu Institute of Technology, Kitakyushu, Japan We studied the effect of the activation of acetylcholine receptor on the epileptogenesis using rat hippocampal slices. Carbachol (30–100 ␮M) can induce ␤ oscillation in the slices. Picrotoxin (PTX)-induced epileptiform discharges were disappeared and ␤ oscillation was induced when carbachol (30 ␮M) was applied. Similar phenomena was observed when carbachol was applied to GABAA receptor antagonist SR95531 (10 ␮M)induced epileptiform discharges. PTX-induced epileptiform discharges were not disappeared by application of simultaneous application of atropine sulfate (30 ␮M) with carbachol. The frequency of PTX-induced epileptiform discharges was increased and the amplitude was decreased by carbachol (1–5 ␮M). Population excitatory postsynaptic potential (pEPSP) was decreased by carbachol (1–5 ␮M). These results suggest that the activation of acetylcholine receptors by carbachol decreased pEPSP, the activation of the pyramidal cells were desynchronized by the decrease in the results carbachol suppresses the hippocampal epileptiform discharges. Research fund: The 21st Century Center of Excellence Program in Kyushu Institute of Technology.