Biomedical subjects

Y Oomura

Publications and source records attributed to Y Oomura.

At least 19 recordsLinked to original sources

PubMed1992

Concurrent measurement of serotonin metabolism and single neuron activity changes in the lateral hypothalamus of freely behaving rat.

To further investigate the activity of serotonin neurons in relation to feeding behavior, the metabolic activity of the serotonergic system and single neuron activity changes in the lateral hypothalamic area (LHA) were investigated concurrently in freely behaving rats. The extracellular concentration of 5-hydroxyindoleacetic acid (5-HIAA), a metabolic product of serotonin in the LHA, began to increase concomitantly with the early stage of nocturnal eating. The increased 5-HIAA returned to the basal level within 3 or 4 h. In conjunction with the increase in serotonin metabolism, activity of 12 out of 30 LHA neurons (40%) increased, whereas it decreased in 7 (23%), and in 11 (37%) it showed no change. An intracerebroventricular injection of lisuride suppressed the increased activity in 7 of the 12 neurons, but had no effect on the others. These results suggest that the concurrent increase in serotonin metabolism and neuron activity changes in the LHA may occur in the early portion of the nocturnal eating period, and may be important in controlling feeding behavior.

Animals↗

PubMed1992

Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices: a sign of neuroprotection.

Using microfluorometry, effects of acidic fibroblast growth factor (aFGF) on the in vitro ischemia-induced intracellular calcium elevation were investigated in gerbil hippocampal slices at 35 degrees C. When slices were superfused with hypoxic and glucose-free medium, the mean latency of the in vitro ischemia-induced calcium elevation was 209 +/- 51 s. The addition of aFGF in medium (25 micrograms/l) delayed the calcium elevation throughout the experiments: the mean latency was 541 +/- 94 s. This retardation in calcium elevation may be indicative of neuroprotective nature of aFGF.

Animals↗

PubMed1992

Acidic fibroblast growth factor prevents death of hippocampal CA1 pyramidal cells following ischemia.

Ischemic insult induces neuronal death in the CA1 subfields of the hippocampus which are designated generally as the most vulnerable brain region. Recent studies have shown that acidic and basic fibroblast growth factors are potent trophic factors that support the survival of neurons in many brain regions including the hippocampus. Here we demonstrate that continuous infusion of acidic fibroblast growth factor into the lateral cerebral ventricles beginning 2 days before ischemia prevents the death of the CA1 pyramidal cells in the hippocampus of gerbils. Furthermore, delayed continuous administration of acidic fibroblast growth factor starting 5 min after ischemia is equally protective. The results suggest a possible physiological function for acidic fibroblast growth factor in the normal support of hippocampal CA1 pyramidal cells and neurons in some other brain regions in considering the broad spectrum of responsive neurons.

Animals↗

PubMed1992

Electrophysiological study of neurotropin-induced responses in guinea pig hypothalamic neurons.

To investigate the direct actions of neurotropin (NSP, a nonproteinaceous extract from inflamed skin of rabbits which is in therapeutic use), intracellular recordings were made from neurons of the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA) in slices of guinea pig brain. In the VMH, NSP, applied by perfusion (0.1-3.0 NU/ml), caused dose-dependent depolarization in 29 of 48 neurons (60%) tested. No change in membrane resistance was observed during the depolarization, which hypothesized that the NSP-induced depolarization might be mediated through the inactivation of the Na-K pump. The NSP-induced depolarization persisted even after the elimination of synaptic activity by perfusion with Ca(2+)-free and high Mg2+ Ringer solution. NSP hyperpolarized the cell membrane of three neurons (6%) while two neurons (4%) showed biphasic responses; transient depolarization followed by long-lasting hyperpolarization. Membrane potential of the remaining 14 neurons was not changed by application of NSP. Of 14 LHA neurons tested for NSP effects, eight (57%) were depolarized, three (21%) were hyperpolarized, and one showed a biphasic response. The present results suggest that NSP significantly modulates hypothalamic neuron activity, and the central modulation of autonomic functions by NSP might be mediated through hypothalamic neurons.

Animals↗

PubMed1992

Sialyl cholesterol enhances the development of grafted neurons and motor recovery.

Trophic actions of alpha-sialyl cholesterol (SC) and its sialidase-tolerant derivative, alpha-(3 beta-hydroxysialyl) cholesterol (SCt), were carried out on the development of midbrain neurons both in vitro and in vivo transplantation studies. Low to moderate concentrations of SC (0.01 to 0.05 micrograms/ml) facilitated neurite extension but had no effects on cell survival of primary cultured midbrain neurons. However, high concentration of SC (0.1 micrograms/ml) disturbed both neurite genesis and cell survival. SCt had a similar effect on midbrain neurons. At higher concentrations, SC and SCt induced concentration-dependent morphological changes in astrocytes from flat to fibrous. The effect on astrocytes was stronger in SCt than SC. At highest concentration tested (20 micrograms/ml), the proliferation of astrocytes was completely blocked, cells became detached and finally died. This effect of SC and SCt was partially blocked by simultaneous application of aFGF. Following dopaminergic cell grafting in vivo, SC and SCt had biphasic effects: a low dose (0.2 mg/kg, SC) enhanced motor recovery at 4 and 6 weeks after transplantation, while the highest dose (20 mg/kg, SC) disturbed motor recovery at all periods tested. These effects on motor recovery were paralleled by an effect on neurite genesis as studied by tyrosine hydroxylase immunostaining. Thus, at low concentrations, SC and SCt are neurotrophic agents that stimulate the development and differentiation of dopaminergic neurons.

Animals↗

PubMed1992

In vivo measurement of hypothalamic serotonin release by intracerebral microdialysis: significant enhancement by immobilization stress in rats.

Intracerebral microdialysis was used to measure extracellular serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus of unanesthetized rats. Increase in the concentration of K+ in the perfusing Ringer solution (70 mM) produced a sharp increase in serotonin release, which was significantly attenuated by omitting Ca2+ from the perfusion medium. Intraperitoneal injection of 5-hydroxytryptophan, a precursor of serotonin, or local perfusion of pargyline, a monoamine oxidase inhibitor, elevated the hypothalamic serotonin. Releasers or uptake inhibitors of serotonin, such as fenfluramine, cocaine, mazindol, or imipramine, when added to the perfusion medium, significantly increased serotonin level, whereas 5-HIAA was unaffected by these substances. Immobilization-stress caused an immediate increase in both the extracellular serotonin and 5-HIAA in the hypothalamus, suggesting that the hypothalamic serotonergic system is activated during immobilization stress. The present study indicates that the brain microdialysis is useful for analysis of local changes in serotonin concentration which directly reflect neuronal transmission.

5-Hydroxytryptophan↗

PubMed1992

A new brain glucosensor and its physiological significance.

The concentration of fibroblast growth factor (FGF), which is found in cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food intake was dose-dependently suppressed by picomole doses of FGF and facilitated by anti-FGF antibody. This suppression was caused by activation of protein kinase C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The ependymal cells released aFGF by responding to glucose increase in CSF after feeding. Released aFGF diffused into the brain parenchyma and was taken by neurons. Passive avoidance was significantly more reliable after aFGF infusion into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF prevented this damage. Thus, aFGF is not only the most potent substance yet found for the suppression of feeding, but it is also extremely effective as a neurotrophic and memory facilitating substance.

Animals↗

PubMed1992

Feeding suppression elicited by electrical and chemical stimulations of monkey hypothalamus.

The effects of electrical (ES) and chemical stimulations of the hypothalamus were investigated in monkeys during bar-press feeding. ES elicited both prolonged and nonprolonged types of suppression of bar-press feeding in hungry animals. Prolonged type suppression persisted for greater than 1 min beyond one or more post-ES trials and was found after ES of the dorsomedial hypothalamus (DMH), the ventromedial hypothalamus (VMH), and the ventromedial part of the lateral hypothalamic area (LHA). Non-prolonged type suppression was observed only during ES at some sites of both in hypothalamic and extrahypothalamic areas. A microinjection of glutamate into the VMH and the DMH, but not into the LHA, was able to reproduce the ES-induced prolonged type suppression. In contrast, the ES of the LHA, but not the VMH and DMH, in a satiated state provoked feeding. The results, together with the previous findings, suggest that the neuronal inhibitory mechanism of feeding exists in the VMH and DMH, while both the neuronal facilitatory and axonal inhibitory mechanisms in the LHA are involved in the feeding regulation, and these mechanisms of the LHA are affected by the hunger/satiety state.

Animals↗

PubMed1992

Responses of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons to chemical stimuli in behaving rhesus monkeys.

1. Extracellular single neuron activity was recorded in the lateral hypothalamic area (LHA) of awake, behaving monkeys, with particular regard to the feeding-related functional characteristics of glucose-sensitive (GS) versus glucose-insensitive (GIS) neurons. Firing rate changes were recorded by means of carbon fiber, multibarreled glass microelectrodes during 1) microelectrophoretic application of various chemicals, 2) gustatory and olfactory stimulation, and 3) a high fixed-ratio schedule (FR) bar press feeding task. 2. In 336 neurons examined, 91 (27%) were suppressed by electrophoretically administered glucose, and so they were designated as GS cells. The 245 neurons (73%) in which the firing rates did not change during glucose applications were pronounced GIS. The 179 GS and GIS cells tested exhibited different responses to the catecholamines (CAs), noradrenaline (NA) and dopamine (DA), both of which are intimately involved in the control of feeding. More GS neurons responded to NA than did GIS cells; the predominant effect of both CAs on GS neurons was inhibition. 3. The taste responsiveness of 111 LHA neurons was examined. Fifty-seven cells (52%) showed responses to gustatory stimulation. Of 50 GS neurons tested, 33 (66%) exhibited firing rate changes to tastes. On the contrary, only 24 (39%) of the 61 GIS neurons examined responded to gustatory stimuli. Activity changes of GS neurons commonly occurred to two or more tastants, in distinction to the relative gustatory specificity shown by GIS cells. 4. Two hundred fifty-six (84%) of the 303 neurons tested responded during one or more phases of the bar press feeding task. Most activity changes occurred during the bar press (BP) and reward (RW) periods, however numerous phasic responses to cue light (CL) and cue tone (CT) were also observed. A higher proportion of the GS neurons showed task-related activity changes than did the GIS cells (77, 95% and 179, 81%, respectively). GS neurons responded more during the BP phase and to the food reward; GIS cells were more responsive during the CL that enabled acquisition and the CT that signaled reward. Thus GS neurons were responsive during the acquisition and consumption of reward, whereas GIS cells responded to external cues signaling both of these events. The gustatory neurons displayed specific task-related activity changes only in the CL (GIS cells) and BP phases (GS neurons), that is, in phases most intimately involved in sensory-motor integration. 5. Two-thirds of the 30 GS neurons tested were responsive to both gustatory and olfactory stimulation as opposed to only one-third of GIS cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1991

Taste and olfactory modulation of feeding related neurons in behaving monkey.

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of beta-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.

Animals↗

PubMed1991

Hypothalamic microdialysis of mazindol causes anorexia with increase in synaptic serotonin in rats.

Brain microdialysis was used to determine if lateral hypothalamic serotonin (5-HT) is involved in the mazindol-induced anorexia in rats. Direct application of mazindol through a microdialysis membrane both significantly increased the 5-HT levels in the lateral hypothalamus and suppressed food intake by fasted rats. The increase in 5-HT concentration was dose related and the concentration of mazindol for half-maximal response was 4.6 microM. Pretreatment with methysergide, a potent 5-HT receptor-blocking agent, significantly antagonized the mazindol-induced anorexia. These results suggest that the anorectic action of mazindol might be mediated, at least in part, through serotonergic mechanisms in the hypothalamus.

Animals↗

PubMed1991

Electrical stimulation of male monkey's midbrain elicits components of sexual behavior.

We electrically stimulated the midbrain of male rhesus monkeys seated in a restraint chair facing the female partners and examined whether sexual behavior could be induced. When the midbrain was stimulated (0.2 ms, 50-500 microA and 50 Hz for 2.5 s), the male monkey touched and held the waist of his partner (latency; 0.9 +/- 0.4 s, mean +/- SD, n = 225), and then mounted her when she responded with presenting her hip toward him. However, this mounting, unlike when the hypothalamus was stimulated, did not lead to thrusting or ejaculation even if the stimulation continued. The sites in the midbrain where the stimulation elicited touching and mounting were the ventral tegmental area, the substantia nigra, the nucleus reticularis mesencephali and the nucleus reticularis pontis oralis et caudalis. Touching and mounting were not elicited when the partner was put away from the male or replaced by submissive male monkeys or humans. The findings suggest that the stimulation-evoked touching and mounting are components of copulatory behavior and that the midbrain structures may be involved in the sexual behavior of male monkeys.

Animals↗

PubMed1991

The effects of interleukin-1 beta on the activity of adrenal, splenic and renal sympathetic nerves in the rat.

The effects of intravenous (i.v.) administration of recombinant human interleukin-1 beta (rhIL-1 beta) on the activity of adrenal, splenic and renal sympathetic nerves were observed in urethane-anesthetized rats. An i.v. injection of IL-1 beta in doses of 10 pg-20 ng per animal (300-400 g, b.w.) resulted in a dose-dependent increase in the activity of the adrenal and splenic nerves, which lasted for more than 2-6 h. On the other hand, the activity of renal nerves showed a transient increase which was followed by a long-lasting suppression after injection of rhIL-1 beta (100 pg, i.v.). An i.v. injection of cyclooxygenase inhibitors (6 mg ibuprofen or 20 mg sodium salicylate) suppressed almost completely the rhIL-1 beta (100 pg)-induced activity in adrenal and splenic nerves. Although rhIL-1 beta (100 pg, i.v.) produced a fall in arterial blood pressure, baroreceptor denervation did not affect the excitatory responses of the adrenal and splenic nerves to rhIL-1 beta. The results suggest the regional differentiation of activity in the visceral sympathetic nerves in response to rhIL-1 beta. The rhIL-1 beta-induced activation of splenic sympathetic nerves implicates their involvement in the modulation of immunity by brain.

Adrenal Glands↗

PubMed1991

Production of antisera to acidic fibroblast growth factor and their application to immunohistochemical study in rat brain.

Antisera against acidic fibroblast growth factor purified from bovine brain were produced in rabbits and used for immunohistochemical study of the rat brain. When examined in an immunospot assay using a nitrocellulose membrane, the best antibody was capable of detecting 80 fmol of acidic fibroblast growth factor but failed to react even with up to 5 pmol of basic fibroblast growth factor. Using this antiserum, the immunohistochemical distribution of acidic fibroblast growth factor was examined in rat brain. Acidic fibroblast growth factor-like immunoreactivity was localized mainly in a subpopulation of ependymal cells and tanycytes, as well as in some glial cells. Positive ependymal cells were observed throughout the walls of ventricles, including the third ventricle and cerebral aqueduct. Immunoreactive processes of tanycytes were found extending from the ventral wall of the third ventricle to the brain parenchyma and surface. The most intense immunostaining was observed in circumventricular organs such as the organum vasculosum laminalis terminalis and the subfornical organ. Particularly in the latter organ, there was an extremely dense plexus of immunoreactive fibers and processes around the wall of capillaries. The present results suggest that the effects of acidic fibroblast growth factor on brain functions may be exerted through the circumventricular organs and/or ependymal cells.

Animals↗

PubMed1991

History of neurophysiology in Japan.

The progress of the neurophysiological research in Japan during the past 45 years is related. Modern Japanese neurophysiology started immediately after the end of World War 2. The introduction of microelectrode techniques contributed greatly to most fields of Japanese neurophysiology. These techniques were used to study most neurophysiological phenomena: sensory physiology including vision, audition, chemical sensitivity, and other modalities; learning and memory. These techniques plus lesions, transplants, and behavioral physiology were used to study circadian rhythm, posture and motor control, and sex. These and other techniques were used to study neural plasticity, immunity, membrane excitability, pain and other psychophysiological functions. The disciplines advanced quickly into multidiscipline approaches into not only electrophysiological, but biophysical, biochemical and immunological research fields. From the past research results our neurophysiologists can be expected to advance rapidly toward further development in the future of Japanese neurophysiology.

Animals↗

PubMed1990

17 beta-estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP.

The process by which 17 beta-estradiol rapidly modulates the excitability of neurons in the ventromedial hypothalamus, a facilitation center of female sexual behavior and satiety center of feeding behavior, through mediation by cyclic nucleotides, was investigated by intracellular recording from the guinea pig brain slice preparations. Two types of short-term responses were produced by depolarization with decreased K+ conductance and hyperpolarization with increased K+ conductance. These two responses were enhanced by the phosphodiesterase inhibitor, isobutylmethylxanthine. However, the specific adenylate cyclase activator, forskolin, enhanced only the depolarization. The analogue of cyclic adenosine 3',5'-monophosphate (cAMP), 8-bromo-cAMP, induced only depolarization, the ionic mechanism of which was similar to that of 17 beta-estradiol. In addition, the possibility of non-specific effects of cyclic nucleotides was precluded by an experiment using an analogue of cyclic guanosine 3',5'-monophosphate (cGMP), 8-bromo-cGMP, which hyperpolarized neurons. Thus, the present study strongly suggests that the production of depolarizing responses of neurons in the hypothalamus produced by estradiol is specifically mediated through cAMP.

1-Methyl-3-isobutylxanthine↗

PubMed1990

Hypothalamic neuronal activity responses to 3-hydroxybutyric acid, an endogenous organic acid.

To elucidate the anorectic action of the endogenous organic acid, 3-hydroxybutyric acid (3-HBA), its effects on neurons in both the rat ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic area (LHA) were examined. Iontophoretic application of 3-HBA significantly facilitated the firing rate of VMH neurons, whereas facilitation and inhibition were observed in the LHA. These responses were specific to the glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA. Intracellular recordings from brain slice preparations revealed that 3-HBA depolarized the cell membrane of the VMH neuron with an associated increase of membrane input resistance. This was similar to the effect of glucose on glucoreceptor neurons in the VMH. These results suggest that 3-HBA may modulate hypothalamic chemosensitive neuron activity as well as function as an endogenous satiety factor.

3-Hydroxybutyric Acid↗

PubMed1990

Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats.

The involvement of a feeding-related endogenous sugar acid, 2-buten-4-olide (2-B4O) on central regulation of gastric acid secretion, and its antiulcer effects on several gastric and duodenal experimental ulcer models were investigated in rats. Spontaneous gastric acid secretion was not affected by 2-B4O at doses below 10 mg/kg. The peripheral secretagogue-stimulated gastric secretions were significantly increased by pretreatment with 2-B4O. Gastric acid secretion induced by 2-deoxy-D-glucose (2-DG) was significantly suppressed by pretreatment with 2-B4O at doses between 0.1 and 100 mg/kg. Gastric and duodenal ulcerations induced by cold stress plus indomethacin, restraint and water immersion stress, pylorus ligation or cysteamine were also inhibited by pretreatment with 2-B4O. The results suggest that antiulcer effects of 2-B4O are due to suppression of gastric acid secretion via reduction of activity of the vagus nerve and gastric-related hypothalamic neurons. Thus, 2-B4O may be useful for treatment of gastroduodenal ulcer.

4-Butyrolactone↗