Clinical analysis of neurotoxity in water intoxication and experimental elucidation of its mechanism

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nara Medical university
• Principal Investigator: KISHIMOTO Toshifumi Nara Medical University, Psychiatry, Professor, 医学部, 教授 (60201456)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Masayuki Nara Medical University, Psychiatry, Research Associate, 医学部, 助手 (30305726) ; NORIYAMA Yoshinobu Nara Medical University, Psychiatry, Research Associate, 医学部, 助手 (20305725) ; KAWABATA Yoko Nara Medical University, Psychiatry, Research Associate, 医学部, 助手 (70145861)
• Project Period (FY): 2001 – 2002
• Keywords: water intoxication / neurotoxity / schizophrenia / anti-psychotic drug / apoptosis

Research Abstract

In order to develop the model rats of water intoxication induced by anti-psychotic drug administration, we tried to establish the system of the continuous infusion into the ventricles. First, male Wistar rat of 160-170g were fed for 21 days, and the basic behavioral data were taken. Next, stainless guide-canule was set in SRO under the anesthesia of pentobarbital. Then, saline was continuously injected by osmotic pump through the canule. After 3 weeks, the injection was confirmed by histopathological observations. Thus, the continuous injection system was developed and applied to the examination of water intoxication.
And apoptosis of neurons was examined by immunohistological method using anti-caspase 3 antibody that recoginizes the fragmented caspase 3, and by Tunnel staining. These observations showed that some neurons were fallen in apoptotic state even in normal rat brain.
Finally, we developed an antibody agaisnt DDB1 which translocates to nucleus at DNA damage, and the observations with the antibody indicated that the apoptotic neurons did not show the DNA repair.

Research Products

• [Publications] Morikawa, M., Kosaka, J., Imai, T., Ohsawa, H., Iida, J., Kishimoto, T.: "A case of general paresis showing marked treatment-associated improvement of cerebellar blood flow by quantitative imaging analysis"Ann.Nucl.Med.. 16. 71-74 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hirayama, T., Kita, T., Ogawa, Y., Ohsawa, H., Yamashita, M., Nakashima, T., Kishimoto, T.: "Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus"Life Sci.. 69. 2147-2156 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Morikawa, M., Kosaka, J., Imai, T., Ohsawa, H., Iida, J., Kishimoto, T.: "A case of general paresis showing marked treatment-associated improvement of cerebellar blood flow by quantitative imaging analysis"Ann. Nucl. Med.. 16. 71-74 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hirayama, T., Kita, T., Ogawa, Y., Ohsawa, H., Yamashita, M., Nakashima, T., Kishimoto, T.: "Effect of chronic treatment with haloperidol on vasopressin release and behavioral changes by osmotic stimulation of the supraoptic nucleus"Life Sci.. 69. 2147-2156 (2001)
  • Description: 「研究成果報告書概要(欧文)」より