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Effects of endogenous steroids on GABAA receptors of chick retina and forebrain expressed in Xenopus oocytes
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EFFECTS OF ENDOGENOUS STEROIDS ON GABAA RECEPTORS OF CHICK RETINA AND FOREBRAIN EXPRESSED IN XENOPUS OOCYTES. Rvuzo Shinaai. Tarou Oaurusu, Yasushi Takeda, Katsumi Hashino. Akemi Yoshida and Katsunori Hoshi. DeDartment of Information Science, Facultv of Enaineerina. Iwate Universitv. Morioka 020.
Several endogenous steroids, such as 5(x-pregan-3tx-ol-20-one (3(x-OH-DHP) and 3tx-pregan-5tr-21In this dial-20-one (THDOC), modulate GABAA receptors and increase the sensitivity to GABA. meeting of the last year we showed that the potency of 3a-OH-DHP to increase ionic currents induced by GABA in trip1 and aiflly2 (i=1,2,3) combinations expressed in Xenopus oocytes is different Since distributions of the receptor subunits in nervous when the u subunit isoform is varied. systems are different depending on the subunit, regional difference in the potency of the steroids GABAA receptors were expressed in Xenopus oocytes by injecting messenger RNA from may be expected. either chick retina or forebrain, and the potency of 3a-OH-DHP and THDOC was investigated by At present an apparent difference between the electrophysiology under voltage clamp conditions. 3tx-OH-DHP at 100 nM augmented GABA actions receptors of the two regions has not been observed. 2.1 (kO.2, n=3) times, and THDOC at 100 nM 1.5 (kO.3, n=2) times for the retinal receptors. Therefore GABAA receptors in the vertebrate reina in viva may be functionally modulated by endogenous steroids.
2-32 Scien ce. V6T lZ5.
EFFECTS OF HALOPERIDOL AND CLOZAPINE ON C-FOS EXPRESSION IN THE RAT FOREBRAIN. KEIJI SATOH AND H.C. FIBIGER*, Deoartment of Psvchiatrv. Shipa Univeristv of Medical tsu 520-21 Ja an *De artment of Ps chia
The proto-oncogene c-fos encodes phosphoprotein Fos and can be activated in the central nervous system by a variety of physiological and pharmacological treatments. Previously, it has been reported that administration of haloperidol, a typical neuroleptic, significantly increase neuronal Fos-immunoreactivity in the rat striatum and many other forebrain regions (Robertson & Fibiger, 1991). To further study the neuronal system that might mediate the therapeutic action of neuroleptics, the distribution of Fos-immunoreactive neurons were investigated in the rat forebrain after a subcutaneous injection of haloperidol (lmg/kg) or clozapine, an atypical neuroleptic (30 mg/kg). Control rats were handled once a day for a week before a vehicle injection. All rats were perfused with 4% parafolmaldehyde, and the brains were postfixed for l-3 days. The brains were cut using a vibratome, and the sections were processed for Fos After an injection of haloperidol, a significant increase in the number of Fos-immunoreactive immunocytochemistry. neurons was observed in the striatum, nucleus accumbens, lateral septal nucleus, central amygdaloid nucleus, paraventricular tbalamic nucleus, and other thalamic nuclei as well as in the hypothalamic regions. Clozapine injection also produced increase in the number Fos-positive neurons in the medial prefrontal cortex, lateral septal nucleus, nucleus accumbens and other forebrain structures except for some regions, such as the striatum. These results indicate that the difference in therapeutic action of neuroleptics may be related to its distinctive pattern of c-fos activation observed in the forebrain structures.
2-33
DISTRIBUTION OF THE NMDA RECEPTOR CHANNEL SUBUNIT mRNAS IN THE DEVELOPING AND MATURE BRAIN. MASAHIKO WATANABE’. YOSHIRO INOUE’, KENJI SAKIMURA2 AND MASAYOSHI MISHINA2, ‘Department of Anatomv. Hokkaido University School of Medicine, Saoporo 060 and 2Department of Neuropharmacoloav, Brain Research Institute, Niiqata University, Niioata 951, Jaoan In situ hybridization analysis have revealed characteristic developmental changes in distribution of the NMDA receptor channel subunit mRNAs in the mouse brain. The ~1 subunit mRNA is expressed only postnatally and distributes widely in the mature brain. On the other hand, the ~2 subunit mRNA is already found in the mantle zone of each brain region at early prenatal stages, but its expression is restricted to the forebrain in the mature brain. The ~3 subunit mRNA appears only postnatally and is found predominantly in the cerebellar granule cells. Both the cl and cl -2 subunit mRNAs are expressed ubiquitously in neurons throughout development. These findings suggest that the NMDA receptor channel complex undergoes reorganization in subunit composition during neural development in various neurons.
EFFECTS OF ENDOGENOUS STEROIDS ON GABAA RECEPTORS OF CHICK RETINA AND FOREBRAIN EXPRESSED IN XENOPUS OOCYTES. Rvuzo Shinaai. Tarou Oaurusu, Yasushi Takeda, Katsumi Hashino. Akemi Yoshida and Katsunori Hoshi. DeDartment of Information Science, Facultv of Enaineerina. Iwate Universitv. Morioka 020.
Several endogenous steroids, such as 5(x-pregan-3tx-ol-20-one (3(x-OH-DHP) and 3tx-pregan-5tr-21In this dial-20-one (THDOC), modulate GABAA receptors and increase the sensitivity to GABA. meeting of the last year we showed that the potency of 3a-OH-DHP to increase ionic currents induced by GABA in trip1 and aiflly2 (i=1,2,3) combinations expressed in Xenopus oocytes is different Since distributions of the receptor subunits in nervous when the u subunit isoform is varied. systems are different depending on the subunit, regional difference in the potency of the steroids GABAA receptors were expressed in Xenopus oocytes by injecting messenger RNA from may be expected. either chick retina or forebrain, and the potency of 3a-OH-DHP and THDOC was investigated by At present an apparent difference between the electrophysiology under voltage clamp conditions. 3tx-OH-DHP at 100 nM augmented GABA actions receptors of the two regions has not been observed. 2.1 (kO.2, n=3) times, and THDOC at 100 nM 1.5 (kO.3, n=2) times for the retinal receptors. Therefore GABAA receptors in the vertebrate reina in viva may be functionally modulated by endogenous steroids.
2-32 Scien ce. V6T lZ5.
EFFECTS OF HALOPERIDOL AND CLOZAPINE ON C-FOS EXPRESSION IN THE RAT FOREBRAIN. KEIJI SATOH AND H.C. FIBIGER*, Deoartment of Psvchiatrv. Shipa Univeristv of Medical tsu 520-21 Ja an *De artment of Ps chia
The proto-oncogene c-fos encodes phosphoprotein Fos and can be activated in the central nervous system by a variety of physiological and pharmacological treatments. Previously, it has been reported that administration of haloperidol, a typical neuroleptic, significantly increase neuronal Fos-immunoreactivity in the rat striatum and many other forebrain regions (Robertson & Fibiger, 1991). To further study the neuronal system that might mediate the therapeutic action of neuroleptics, the distribution of Fos-immunoreactive neurons were investigated in the rat forebrain after a subcutaneous injection of haloperidol (lmg/kg) or clozapine, an atypical neuroleptic (30 mg/kg). Control rats were handled once a day for a week before a vehicle injection. All rats were perfused with 4% parafolmaldehyde, and the brains were postfixed for l-3 days. The brains were cut using a vibratome, and the sections were processed for Fos After an injection of haloperidol, a significant increase in the number of Fos-immunoreactive immunocytochemistry. neurons was observed in the striatum, nucleus accumbens, lateral septal nucleus, central amygdaloid nucleus, paraventricular tbalamic nucleus, and other thalamic nuclei as well as in the hypothalamic regions. Clozapine injection also produced increase in the number Fos-positive neurons in the medial prefrontal cortex, lateral septal nucleus, nucleus accumbens and other forebrain structures except for some regions, such as the striatum. These results indicate that the difference in therapeutic action of neuroleptics may be related to its distinctive pattern of c-fos activation observed in the forebrain structures.
2-33
DISTRIBUTION OF THE NMDA RECEPTOR CHANNEL SUBUNIT mRNAS IN THE DEVELOPING AND MATURE BRAIN. MASAHIKO WATANABE’. YOSHIRO INOUE’, KENJI SAKIMURA2 AND MASAYOSHI MISHINA2, ‘Department of Anatomv. Hokkaido University School of Medicine, Saoporo 060 and 2Department of Neuropharmacoloav, Brain Research Institute, Niiqata University, Niioata 951, Jaoan In situ hybridization analysis have revealed characteristic developmental changes in distribution of the NMDA receptor channel subunit mRNAs in the mouse brain. The ~1 subunit mRNA is expressed only postnatally and distributes widely in the mature brain. On the other hand, the ~2 subunit mRNA is already found in the mantle zone of each brain region at early prenatal stages, but its expression is restricted to the forebrain in the mature brain. The ~3 subunit mRNA appears only postnatally and is found predominantly in the cerebellar granule cells. Both the cl and cl -2 subunit mRNAs are expressed ubiquitously in neurons throughout development. These findings suggest that the NMDA receptor channel complex undergoes reorganization in subunit composition during neural development in various neurons.