Neuroscience research
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Neuroscience research · Aug 2005
Comparative StudyChronic stimulation of GABAA receptor with muscimol reduces amyloid beta protein (25-35)-induced neurotoxicity in cultured rat cortical cells.
The present study was performed to examine how the stimulation of gamma-aminobutyric acid (GABA) receptor affects amyloid beta protein (25-35) (Abeta (25-35)), a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. Abeta (25-35) produced a concentration-dependent reduction of cell viability, which was significantly reduced by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, verapamil, an L-type Ca(2+) channel blocker, and N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor. Pretreatment with muscimol, a GABAA receptor agonist, over a concentration range of 0.1-10microM 24h before the treatment with 10microM Abeta (25-35) showed concentration-dependent inhibition on the Abeta (25-35)-induced neuronal apoptotic death. ⋯ These neuroprotective effects of muscimol (1microM) were completely blocked by the simultaneous treatment with 10microM bicuculline, a GABAA receptor antagonist, indicating that the protective effects of muscimol were due to GABAA receptor stimulation. When, however, treated just 15min before the treatment with Abeta (25-35), muscimol (1microM) did not show any protective effect against Abeta (25-35) (10microM)-induced neurotoxicity in cultured neurons. These results suggest that the chronic activation of GABAA receptor may ameliorate Abeta-induced neurotoxicity by interfering with the increase of [Ca(2+)]c, and then by inhibiting glutamate release, generation of ROS and caspase-3 activity.
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Neuroscience research · Apr 2005
Comparative StudyPreemptive analgesia by zaltoprofen that inhibits bradykinin action and cyclooxygenase in a post-operative pain model.
The post-operative pain state results from a barrage of primary afferent inputs exposed to products of tissue damage such as bradykinin and prostaglandins and the central sensitization by the continuing inputs. This provides the rationale for preemptive analgesia, whereby the blockade of primary afferent inputs prior to injury may result in a reduction of post-operative pain. 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl) propionic acid (zaltoprofen) is a unique compound that inhibits cyclooxygenase (COX) and exhibits anti-bradykinin activity. The present study evaluated the preemptive analgesic effect of zaltoprofen in a post-operative pain model produced by plantar incision. ⋯ While the bradykinin B1 antagonist des-Arg10-HOE-140, the selective COX-1 inhibitor SC-560, and the selective COX-2 inhibitor celecoxib did not affect post-operative pain, the B2 antagonist HOE-140 dose-dependently relieved the post-operative pain at 2-200 microg/kg with a time course similar to that of zaltoprofen. The B2 receptor mRNA was expressed in the hindpaw and the expression did not change before and 24 h after surgery. These results suggest that zaltoprofen produces the preemptive analgesic effect peripherally by blocking the B2 pathway.
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Neuroscience research · Oct 2004
Transient increase of TUNEL-positive cells on postnatal day 20 in the developing rat olfactory bulb.
In the developing central nervous system, apoptosis plays an important role in the normal organization of the neuronal circuit. The timing of neurogenesis, proliferation, and migration of the neurons in the developing olfactory bulb (OB) is well studied; however, the involvement of apoptosis in this process is not fully understood. ⋯ Although the number of TUNEL-positive cells was relatively small during the embryonic period, it gradually increased after birth, and peaked on postnatal day 20 with statistical significance, especially in the granule cell layer of the main OB. This transient increase of TUNEL-positive cells on postnatal day 20 may be involved in a critical event during maturation of the OB.
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Neuroscience research · Sep 2004
A morphometric study of the progressive changes on NADPH diaphorase activity in the developing rat's barrel field.
The distribution of NADPH diaphorase (NADPH-d)/nitric oxide synthase (NOS) neurons was evaluated during the postnatal development of the primary somatosensory cortex (SI) of the rat. Both cell counts and area measurements of barrel fields were carried out throughout cortical maturation. In addition, NADPH-d and cytochrome oxidase (CO) activities were also compared in both coronal and tangential sections of rat SI between postnatal days (P) 10 and 90. ⋯ The dendritic arborization of NADPH-d neurons became more elaborated during barrel development. In all ages evaluated, the number of NADPH-d cells was always higher in septa than in the barrel hollows. Both high neuropil reactivity and differential distribution of NADPH-d neurons during SI development suggest a role for nitric oxide throughout barrel field maturation.