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Volume 113 (1999)
- Issue 6 Pages 331-
- Issue 5 Pages 289-
- Issue 4 Pages 201-
- Issue 3 Pages 133-
- Issue 2 Pages 73-
- Issue 1 Pages 7-
Volume 113, Issue 2
Displaying 1-4 of 4 articles from this issue
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Yasunori HAYASHI1999 Volume 113 Issue 2 Pages 73-83
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe metabotropic glutamate receptors (mGluRs) consist of at least eight different subtypes. However, the lack of specific ligands for this class of receptors limited the characterization of their roles. In this study, a series of glutamate derivatives was systematically tested for agonist and antagonist activities for the mGluR subtypes, individually expressed in cell lines. Among various compounds tested, (2S, 1'R, 2'R, 3'R)-2 (2, 3-dicarboxycyclopropyl) glycine (DCG-IV) was found to be an effective agonist for mGluR2 and α-methyl-4-carboxyphenylglycine (αM4CPG) was found to be an antagonist for both mGluR1 and mGluR2. Using DCG-IV, I showed that mGluR2 mediates presynaptic inhibition of GABA release from granule cells at the dendrodendritic synapse of the accessory olfactory bulb (AOB). This mechanism was considered to relieve a mitral cell from GABAergic inhibition and, furthermore, to be involved in lateral inhibition of surrounding mitral cells and thus enhancing the signal/noise ratio of olfactory sensation. I also show that an activation of mGluR2 in AOB by infusion of DCG-IV induces olfactory memory, which can mimic the pregnancy block phenomenon of female mice. This is the first report of a role of specific subtype of mGluR in the central nervous system.View full abstractDownload PDF (11610K) -
Masato NANRI, Hiroshi WATANABE1999 Volume 113 Issue 2 Pages 85-95
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSWe have established a chronic cerebral hypoperfusion model that is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus 1-3 days after 2VO and infarctions in the striatum 7 days after 2VO. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2). Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after 2VO. Marked increase in GFAP staining in astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. In the 8-arm radial maze performance, the 2VO rats showed a higher rate of errors than the sham-operated control during repeated training periods. THA (9-amino-1, 2, 3, 4-tetrahydroacridine), a cholinesterase inhibitor and GTS-21 (3-(2, 4-dimethoxybenzylidene)-anabaseine dihydrochloride), a central nicotinic acetylcholine-receptor agonist improved the learning impairment in the radical maze task of 2VO rats. GTS-21 administration exerted a protective effect against the neuropathological changes that followed 2VO. Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.View full abstractDownload PDF (14710K) -
Hideaki HARA1999 Volume 113 Issue 2 Pages 97-111
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThis overviews recent understanding of the mechanisms of apoptosis on ischemia-induced neuronal cell death. Apoptosis is a prominent feature of the developing nervous system. Several lines of evidence suggest that apoptosis is also an important mechanism of cell death in adult brain in acute or chronic diseases such as stroke and Alzheimer's disease. In animal models of stroke, markers of apoptosis such as cytoplasmic and nuclear condensation and DNA fragmentation appear in neurons. A variety of physiological and pathological stimuli can activate signal-transduction pathways that result in the sequential proteolytic activation of caspase family members. The activation of caspases can be inhibited by several molecules, including peptide aldehydes (caspase-1 and/or caspase-3 inhibitors) and crmA that target the active-site cysteine of caspase family members, Bcl-2, IAP (inhibitor of apoptosis protein) and NAIP (neuronal apoptosis inhibitory protein). Once activated, caspase-1 protease can activate the caspase family members and hydrolyze a discrete set of cellular targets. Poly (ADP-ribose) polymerase (PARP), which appears to facilitate apoptosis, was recognized as a substrate of activated caspase-3. These results suggest that caspase family, bcl-2 family, IAP family and substrates such PARP contribute to mechanisms of cell death in ischemic brain injury. Inhibition of the caspase family, particularly by non-peptide inhibitors that cross the bloodbrain barrier and easily penetrate neurons and glia, could provide novel treatments for stroke and other forms of brain and spinal cord injury in humans.View full abstractDownload PDF (17132K) -
Hiroyuki KAMEI, Yukihiro NODA, Toshitaka NABESHIMA1999 Volume 113 Issue 2 Pages 113-120
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSPsychological stress is believed to be implicated in the etiology of affective disorders such as anxiety and depression. To date, a wide range of behavioral responses including analgesia and motor suppression induced by various physiological stressors such as footshock, forced swimming and immobilization have been investigated in animals. However, there is little information concerning behavioral changes in psychological stress. This article describes the experimental procedures and the characteristics of motor suppression in psychological stress, defined as conditioned fear stress (CFS). Mice exhibit a marked suppression of motility when they are re-placed in the same environment in which they had previously received an electric footshock. This motor suppression is regarded as a conditioned emotional response to the environment associated with previous footshock. The motor suppression in CFS is attenuated by sigma receptor agonists such as (+)-N-allylnormetazocine and dextromethorphan, whereas typical anxiolytics (diazepam and chlordiazepoxide) and antidepressants (imipramine and fluoxetine) have no effect. These findings suggest that the CFS model may be useful for investigating the pathogenesis of affective disorders, particularly those considered to be treatment resistant, and for developing their novel therapeutic drugs.View full abstractDownload PDF (8784K)
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