PubMed Health⌕ Search

Biomedical subjects

Hirotaka Onoe

Publications and source records attributed to Hirotaka Onoe.

11 recordsLinked to original sources
PubMed2006

Neuroprotection by a central nervous system-type prostacyclin receptor ligand demonstrated in monkeys subjected to middle cerebral artery occlusion and reperfusion: a positron emission tomography study.

BACKGROUND AND PURPOSE: Recently, we found that a novel subtype of prostacyclin (PGI(2)) receptor clearly distinct from the peripheral subtype in terms of ligand specificity is expressed in the central nervous system (CNS). (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to be a specific ligand for this CNS-type PGI(2) receptor. Previously, we demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on primary cultured hippocampal neurons, indicating its neuroprotective effect against ischemic insults occurs via direct action on CNS-type PGI(2) receptor. METHODS: Local cerebral hemodynamics and oxygen metabolism were measured simultaneously by using positron emission tomography with the (15)O steady-state method, before and up to 18 hours after 3-hour transient MCAO reperfusion in cynomolgus monkeys. Methyl ester of 15R-TIC (50 microg/kg, n=4) or its vehicle (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of MCAO and continuously infused for 5 hours (50 microg/kg per hour). RESULTS: Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3-hour MCAO. Positron emission tomography results showed 15R-TIC significantly reduced the volume of "infarct" region of interest and attenuated the decrease in cerebral metabolic rate of oxygen and oxygen extraction fraction, and these protective effects were not attributable to improvement of cerebral circulation. CONCLUSIONS: These results suggest that 15R-TIC has a potent neuroprotective effect against focal cerebral ischemia in a monkey MCAO via its direct action on CNS-type PGI(2) receptors.

Animals↗
PubMed2006

Reduced responsiveness is an essential feature of chronic fatigue syndrome: a fMRI study.

BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated by a number of researchers, it remains poorly understood. METHODS: Using functional magnetic resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual search task. RESULTS: Responsiveness of the task-dependent brain regions was decreased after the fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period, although responsiveness of auditory cortices remained constant in the normal subjects, it was attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was positively correlated with the subjective sensation of fatigue as measured using a fatigue visual analogue scale, immediately before the magnetic resonance imaging session. CONCLUSION: Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task.

Adult↗
PubMed2006

A potent non-monoaminergic paradoxical sleep inhibitory system: a reverse microdialysis and single-unit recording study.

Using reverse microdialysis and polygraphic recordings in freely moving cats, we investigated the effects on sleep-waking states of application of excitatory and inhibitory amino acid agonists, cholinergic agonist and monoamines to the periaqueductal grey and adjacent mesopontine tegmentum. Single-unit recordings during behavioural states were further used to determine the neuronal characteristics of these structures. We found that muscimol, a GABAA receptor agonist, induced a significant increase in paradoxical sleep (PS) only when applied to a dorsocaudal central tegmental field (dcFTC) located just beneath the ventrolateral periaqueductal grey. In this structure, both kainic and N-methyl-aspartic acids caused a dose-dependent increase in wakefulness (W) and decrease in both slow-wave sleep (SWS) and PS. Norepinephrine and epinephrine, and to a lesser extent histamine, also increased W and decreased SWS and PS, whereas serotonin, dopamine and carbachol, a cholinergic agonist, had no effect. Two types of neurones were recorded in this structure, those exhibiting a higher rate of tonic discharge during both W and PS compared with during SWS, and those showing a phasic increase in firing rate during both active W and PS. Both types of neurones showed a gradual increase in unit activity during PS. Our study demonstrated for the first time that the ventrolateral periaqueductal grey and dcFTC play different roles in behavioural state control, that the dcFTC neurones are critically involved in the inhibitory mechanisms of PS generation, playing a central part in its maintenance, and that these neurones are under the control of GABAergic, glutamatergic, adrenergic and histaminergic systems.

Action Potentials↗
PubMed2004

Reduction of serotonin transporters of patients with chronic fatigue syndrome.

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET). Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients. Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

Adult↗
PubMed2004

A dynamic shift of neural network activity before and after learning-set formation.

Learning-set (LS) is a property of insight and hypothesis testing characterized by the ability to solve novel problems based on previous experiences with problem solving. However, the neural organization and mechanisms underlying LS remain unclear. To further characterize this process, positron emission tomography (PET) studies with [15O]H2O were performed to measure regional cerebral blood flow (rCBF) during the learning phase of the two-choice visual discrimination task under the LS paradigm in rhesus monkeys. When comparing studies before and after LS formation, the orbitofrontal and lateral prefrontal cortices were differentially activated, and functional connections between these structures and the striatum, which contributes to habit learning, were altered. We conclude that changes in the lateral prefrontal cortex during problem solving may contribute to the executive function of working memory and also inhibit control of a primitive learning system, thereby promoting LS formation.

Animals↗
PubMed2004

Increase in reaction time for solving problems during learning-set formation.

Six rhesus monkeys were tested for a change in reaction time for problem-solving during a learning-set task, in which they showed progressive improvement in the rate of learning successive problems of visual discrimination. To evaluate the processing time for cognitive processes in problem-solving, the differences in release latency and movement time between the visual discrimination task and the visuomotor control task were defined. In their first experience, the monkeys required several hundreds of trials for solving the problem, and the Deltarelease latency was constant throughout the learning. With increasing experience, they solved problems within fewer trials than with the first problem. At this stage, the Deltarelease latency was high at the beginning and then decreased. The rise in the Deltarelease latency within the learning acquisition period increased depending on the amount of experience with problems they had solved, whereas the Deltamovement time within that period was not significantly affected by the experience with problems. The present findings suggest that the number of problem-solving experiences could promote profound cognitive processing, which may be related to a conceptual representation that actualizes the flexibility of learning, namely, the learning set.

Animals↗
PubMed2003

Activation of the anterior cingulate gyrus by 'Green Odor': a positron emission tomography study in the monkey.

The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), 'green odor', is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey.

Aldehydes↗
PubMed2003

[Non-human primate behaviors as models for development of higher cognitive functions].

Non-human primate behaviors have a special value for the neurobiological study of the development of higher cognitive functions of humans, because of the near evolutional relation between two species. We surveyed results and futures of neurobiological studies of a retrieval task, a learning-set and a self-injurious behavior expressed by non-human primates. On the retrieval task that is related to the development of inhibitory control, it was revealed a hierarchical ordering of inhibitory control processes in which the distinct neuronal circuits were involved. On the learning-set that is related to the development of abstract thinking, neural circuits for the individual learning dramatically changed from an automatic process to a cognitive process depending on the learning-set formation. The self-injurious behavior is expressed during early normal development in humans, and no other animals but non-human primates express it without administration of drugs. For that behavior, probable change in interactions of multiple monoaminergic systems was suggested as its underlying causes. Further studies on development of higher cognitive functions using non-human primates could be required for understanding the nature of human cognition.

Animals↗
PubMed2002

Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain.

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation. Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate. When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann's area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum. These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

Acetylcarnitine↗
PubMed2002

Functional anatomy of chemical senses in the alert monkey revealed by positron emission tomography.

Functional imaging technique using positron emission tomography (PET) has made it possible to localize functional brain regions in the human brain by detecting changes in regional cerebral blood flow (rCBF). Performing PET studies in the monkey will aid in integrating monkey electrophysiological research with human PET studies. We examined changes in rCBF during olfactory or combined olfactory and gustatory (flavour) stimulation using PET in the alert rhesus monkey. Olfactory or flavour stimulation with acetic acid or apple increased rCBF in the prepyriform area, substantia innominata and amygdala. Besides these areas, flavour stimulation increased rCBF in the anterior insula and frontal operculum, orbitofrontal cortex, inferior frontal gyrus and cerebellum. Apple odour or flavour stimuli increased rCBF in the inferior occipital gyrus in addition to the above areas. These findings suggest that the increases of rCBF in response to neural activities in the primary olfactory and gustatory cortices are detectable by the use of PET. In addition, regions activated by apple stimuli suggest that higher brain function might be detected with PET in the alert monkey.

Animals↗