Search PubMed⌕ Search

Biomedical subjects

M Asanuma

Publications and source records attributed to M Asanuma.

At least 109 records · Page 6Linked to original sources
PubMed1991

Distribution of the beta-2 adrenergic receptor messenger RNA in the rat brain by in situ hybridization histochemistry: effects of chronic reserpine treatment.

We studied the distribution of the rat brain beta-2 adrenergic receptor (AR) mRNA, and the effects of monoamine depletions by chronic reserpine treatment using in situ hybridization histochemistry. In the control group, high level signals of beta-2 AR mRNA were observed in the parietal, frontal and piriform cortices, the medial septal nuclei, the olfactory tubercle, and the midbrain. Moderate signals were found in the striatum, the retrosplenial cortex, the hippocampus, and the thalamic nuclei. After chronic reserpine treatment, beta-2 AR mRNA levels were increased in many brain regions. The large increases were seen in the hippocampus, all thalamic nuclei, the amygdaloid nuclei, and the midbrain, followed by the striatum and the occipital cortex. The receptor up-regulation resulting from chronic monoamine depletion may be due to these increases in beta-2 AR mRNA, indicating that this up-regulation may be caused by increased receptor production rather than decreased receptor degradation.

Animals↗
PubMed1991

Loss of N-methyl-D-aspartate (NMDA) receptor binding in rat hippocampal areas at the chronic stage after transient forebrain ischemia: histological and NMDA receptor binding studies.

Although neuronal death following brain ischemia was originally considered to be due to an energy deficiency resulting from an impaired respiratory chain, the observation of "delayed neuronal death" indicated some other factor. It is believed that delayed neuronal death after transient forebrain ischemia appears as a result of release of glutamate, an excitatory amino acid. In the present study, transient ischemia for 20 minutes in a rat four-vessel occlusion model was induced, and serial changes in histology and N-methyl-D-aspartate receptor (NMDA-R) binding were evaluated up to the chronic stage. Destruction of pyramidal cells and extensive astrocytic proliferation in the CA1 area of the hippocampus was completed by 10 days after cerebral ischemia followed by cerebral blood recirculation. However, the glutamate receptor subtype, NMDA-R, showed no change in all brain regions until after 10 days, but decreased in the hippocampus to 50% after 21 days despite no evidence of histological progression of neuronal death. The results show that the time course for appearance of light microscopic damage in the hippocampal region does not parallel that for depletion of NMDA-R binding sites.

Animals↗
PubMed1991

Effects of beta-adrenergic blocking agents on specific binding of [3H]D-Ala2-Met5-enkephalinamide and [3H]naloxone.

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.

Adrenergic beta-Antagonists↗
PubMed1991

[Chronic administration of bifemelane hydrochloride increases somatostatin receptor binding in aged rat brain].

Changes in the distribution and densities of somatostatin receptors (SS-R) in young adult and aged rat brain and the effects of chronic administration of bifemelane hydrochloride (bifemelane) on these changes were studied by in vitro quantitative autoradiography of iodinated [Tyr11] SS-14. SS-R was highest in density in the amygdala, followed by the cingulate cortex, temporal cortex, frontal cortex, hippocampus and septal nucleus in the young adult rats. In contrast, SS-R binding was markedly reduced in the frontal cortex, temporal cortex, cingulate cortex, hippocampus, amygdala and septal nucleus of aged rats compared to young adult rats. However chronic administration of bifemelane significantly increased SS-R binding in the frontal cortex, temporal cortex, cingulate cortex, hippocampus and septal nucleus of aged rats without effects on young adult rats. This bifemelane-induced increase in SS-R is considered to have important implications in the mechanism of the therapeutic efficacy of bifemelane.

Aging↗
PubMed1991

Dopamine deficiency in the weaver mutant mouse: an animal model of olivopontocerebellar atrophy.

The dopamine system in weaver mutant mice, a model of cerebellar atrophy, was studied. Dopamine levels of 6-week-old weaver mice were 37%, 44%, 34%, and 41% of levels in age-matched controls in the cerebral cortex, hippocampus, septal region and striatum, respectively. Noradrenaline levels did not differ from controls. This study shows that weaver mice have specific deficiencies in the dopamine system.

Analysis of Variance↗
PubMed1991

Chronic bifemelane hydrochloride administration enhances muscarinic cholinergic receptor binding in the senescent rat brain.

In senescent rats, the binding ability of muscarinic cholinergic receptors (MCR) was markedly decreased in the cerebral cortex, hippocampus, thalamus, and the striatum compared with young adult rats. This decrease was markedly improved by chronic administration of bifemelane hydrochloride (bifemelane). In view of the findings that bifemelane markedly inhibits the decrease in acetylcholine (ACh) associated with cerebral ischemia, and that it improves amnesia induced by scopalamine, it may be inferred that bifemelane acts on the pre- and post-synaptic ACh neuronal systems. It may improve memory disturbance due to aging or cerebral ischemia, decreased conscious level, and decreased motor function.

Aging↗
PubMed1990

Alterations of somatostatin and its modulation by levodopa in MPTP-treated mouse brain.

We examined the changes in the concentrations of neuropeptides in various regions of the mouse brain 1, 2 or 6 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) and further examined the effects of levodopa injections (200 mg/kg i.p.) for 14 days starting 4 weeks after MPTP treatment on regional somatostatin (SRIF) concentrations. Substance P, cholecystokinin-octapeptide and thyrotropin-releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment, whereas the SRIF concentration increased 1 week after MPTP treatment but decreased thereafter, showing a marked decrease in the striatum and hippocampus after 6 weeks. In the striatum, the decreased concentration of SRIF recovered to the normal level with levodopa injections. This SRIF depletion could be a change secondary to dopamine depletion. On the other hand, in the cerebral cortex, while showing no change in the SRIF concentration after MPTP treatment, the concentration decreased significantly with levodopa injections. In the hippocampus, the decreased SRIF levels were still low after levodopa treatment. Since it has been reported that SRIF concentrations are significantly reduced in the frontal cortex and hippocampus of demented parkinsonians and patients with senile dementia of the Alzheimer type and that levodopa treatment induced various psychiatric side effects, the results of the present study suggest some relationship among levodopa treatment, SRIF depletion and the demented state.

Animals↗
PubMed1990

Regional responses of rat brain opioid receptors upon castration and testosterone replacement.

Regional responses of rat brain opioid receptors (Op-Rs) upon castration and testosterone replacement were studied using [3H]naloxone (NAL) binding for u-type and [3H]D-Ala2-methionine-enkephalin (ENK) binding for delta-type Op-R. Castration itself produced an increase in specific NAL and ENK binding in the olfactory bulb and thalamus + midbrain. In the hypothalamus, specific ENK binding was increased without any change in NAL binding. After the testosterone replacement in castrated rats, specific NAL binding was decreased and returned to the control level in the thalamus + midbrain, but remained high in the olfactory bulb. Specific ENK binding was decreased and returned to the control level in the olfactory bulb, hypothalamus and thalamus + midbrain. These results indicated that there are regional differences between u- and delta-type Op-R responses to castration and testosterone replacement. Op-R subtypes were regulated differentially by endogenous hormonal changes, such as testosterone.

Animals↗
PubMed1990

[Effect of flunarizine hydrochloride on striatal D-2 dopamine receptors].

Flunarizine hydrochloride (FZ) is used to improve cerebral circulation and possesses Ca antagonistic effects. In recent years, this drug has been reported to induce parkinsonism and depressive symptoms as side effects, particularly in the elderly. Effects of FZ on dopamine receptors of the rat striatum were studied by radiolabeled receptor assay to clarify the mechanism of onset of parkinsonism in response to FZ. FZ was found to directly and competitively affect D-2 receptors without affecting D-1 receptors. Furthermore, the effect of FZ on D-2 receptors was found to be antagonistic based on the finding that the displacement curve for FZ in the binding of [3H]spiperone to D-2 receptors remained unchanged even after the addition of GppNHp. The effect of FZ on the D-2 receptors in aged rats was more marked than that in young-adult rats. In addition, the tertiary structures of FZ and the anti-schizophrenic agents, pimozide and haloperidol, were examined using computer graphics. FZ was found to have a tertiary structure highly analogous to pimozide and haloperidol, and FZ also had an alkyl structure linking a fluorophenyl group and a nitrogen atom, believed to be particularly necessary for the binding of anti-schizophrenic agents to D-2 receptors. These results may contribute to clarifying the mechanism of onset of parkinsonism in response to FZ, especially in the elderly.

Age Factors↗
PubMed1990

Comparison of formaldehyde-preperfused frozen and freshly frozen tissue preparation for the in situ hybridization for alpha-tubulin messenger RNA in the rat brain.

In situ hybridization histochemistry, using the alpha-tubulin oligonucleotide probe, was performed employing two tissue freezing methods, the preperfuse-freezing method and the freshly frozen method, to evaluate methodological differences in the messenger RNA (mRNA) levels of the brain. The mRNA levels in the sections from the freshly frozen groups were lower than those in the preperfused group, particularly in the cerebral cortex, the striatum, the hippocampal Ca1 and CA4 fields, and the habenular nuclei. Therefore, employing the freshly frozen method, there is a possibility that the mRNA levels in these regions may be underestimated. The hybridization signals of groups placed on an ice-bed for 5 min and 15 min were lower than those of the immediately frozen group in the cingulate, the temporal, and the retrosplenial cortex, the CA1 field, and even in the medial and the lateral thalamic nuclei where no significant difference was seen between the perfused group and the immediately frozen group of tissues. When employing the freshly frozen method, the removed brain should be frozen as fast as possible and the period from decapitation to freezing should be kept strictly constant.

Animals↗
PubMedDate not supplied

Calcium antagonist flunarizine hydrochloride affects striatal D2 dopamine receptors in the young adult and aged rat brain.

The calcium (Ca) antagonist flunarizine hydrochloride (FNZ) has been reported to induce parkinsonism, especially in the elderly. The effects of FNZ on dopamine receptors in rat striatal membranes, especially in aged rats, were studied using radiolabeled receptor assay. Similar displacing potencies in [(3)H]spiperone bindings were exhibited for FNZ and the Ca antagonists verapamil and nicardipine. FNZ was found to directly and competitively effect D2 receptors (D2-Rs) as an antagonist, without effecting D1 receptors. Furthermore, the washing of preoccupied membranes revealed that FNZ has a long-acting potent effect on D2-Rs. The comparative study of FNZ and sulpiride in young-adult and aged rats showed that the effect of FNZ on D2-Rs was more marked in aged rats. These results might be related to FNZ-induced parkinsonism and its high incidence in the elderly.

Journal Article↗
PubMedDate not supplied

Effects of chronic codergocrine mesylate administration on the brain somatostatinergic system in aged rats.

Codergocrine mesylate (dihydroergotoxine; DHET), which is an ergot derivative, has been reported to counteract some age-induced impairments in brain function, but the mechanism of these effects is not known. We examined the effect of chronic DHET administration on the somatostatinergic system in the brains of aged rats. Intraperitoneal injections of DHET (1 mg/kg per day) or of vehicle were given to aged rats for 14 days, and resulted in a significant increase in somatostatin (SOM) receptor binding in all six brain regions examined except the hindbrain. DHET had no effect on SOM receptor binding in the brains of young-adult rats. However, the SOM concentration in aged rats was nearly identical to that in young-adult rats and the SOM concentration in different brain areas did not change after chronic administration of DHET. Thus, the present results suggest that chronic administration of DHET can ameliorate at least one of the age-induced impairments of brain somatostatinergic function.

Journal Article↗
PubMedDate not supplied

Cholinergic deficits in aged rat brain are corrected with nicergoline.

Choline acetyltransferase (CAT) and muscarinic cholinergic receptor (MCR) activities are markedly reduced in aged as compared with young-adult rat brain. Nicergoline was found to correct these reduced activities in most regions of the brain, especially in the cerebral cortex and hippocampus. Chronic administration of nicergoline had no effect on CAT activity or MCR binding in young-adult rat brain. Nicergoline thus appears to have a specific therapeutic effect on cholinergic functions in aged rat brain, where it acts both pre-synaptically and post-synaptically.

Journal Article↗
PubMedDate not supplied

Effects of repeated administration of rolipram, a cAMP-specific phosphodiesterase inhibitor, on acetylcholinergic indices in the aged rat brain.

The effects of repeated treatment of rolipram, a cAMP specific phosphodiesterase inhibitor (0.1 mg/kg/day i.p., 14 days), on several neuronal cholinergic indices, especially on those in aged rats were examined. In young-adult rats, rolipram treatment increased choline acetyltransferase (ChAT) activity (V(max)value) in the striatum as well as in thalamus + midbrain, whereas it decreased choline esterase activity in the hippocampus. The ChAT activity (V(max)value) and the M1-R binding (B(max)value) in the aged control rats were significantly reduced in all the brain regions examined, compared with the young-adult rats, but consecutive rolipram treatment ameliorated the reductions of both indices in the frontal cortex and the hippocampus to approximately the young-adult control levels. Since high membrane binding site concentrations for rolipram itself were revealed in the frontal cortex and the hippocampus, where the rolipram treatment showed ameliorating effects on the ChAT activity and the M1-R binding, the present findings indicate that repeated rolipram administration easily affects these two brain regions. Thus, repeated rolipram administration could restore both the presynaptic ChAT activity and the postsynaptic muscarinic cholinergic M1-R binding which are decreased with aging.

Journal Article↗
PubMedDate not supplied

Abnormalities in muscarinic cholinergic receptors and their G-protein coupling systems in the cerebral frontal cortex in Alzheimer's disease.

Receptor binding assays and in vitro macroautoradiography were used to analyze muscarinic cholinergic receptors (MCR) in the cerebral frontal cortex of Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT), and age-matched control brains at autopsy. Total MCR binding, detected by [(3)H]quiniclinidyl benzilate binding, did not differ significantly between the 3 groups. The concentrations of M1 subtype (M1-R), detected by [(3)H]pirenzepine binding, and high affinity state MCRs, however, were significantly lower in AD than in control and SDAT frontal cortices. No differences were detected in the affinity of these receptors for their ligands. The MCRs in AD frontal cortex were more sensitive to the agonist carbachol than were control MCRs. Autoradiography revealed a complete destruction of the laminar distribution of MCR and M1-R in AD and SDAT frontal cortices. Forskolin and phorbol ester binding sites, used to analyze second messenger systems, were significantly and markedly reduced in AD frontal cortex. In addition, coupling between MCR and second messenger systems was supersensitive in AD frontal cortex. Our findings that there are alterations in the structural distribution of MCR as well as reductions and abnormalities in second messenger systems in AD cerebral frontal cortex, suggest that drug therapy with acetylcholine precursors, choline esterase inhibitors and muscarinic agonists cannot eliminate symptoms in dementia patients. Furthermore, they point out the need for techniques to diagnose the disease prior to disintegration of the neuronal network, and the need for therapies to delay or prevent the progression of structural changes.

Journal Article↗