Noriyuki Yuyama

Suppression of stress immobilization-induced phosphorylation of ERK 1/2 by biting in the rat hypothalamic paraventricular nucleus

We have previously reported that acute immobilization stress induces Fos protein. Fos protein is generally used as a marker for neuronal activity and has been linked to phosphorylation of extracellular signal-regulated protein kinase 1/2 (pERK1/2), in the hypothalamic paraventricular nucleus (PVN). Biting behavior during the period of stress reduced the expression of Fos protein. The present immunohistochemical study was designed to determine whether acute immobilization stress induces pERK1/2 in the PVN, and whether the stress-induced pERK1/2 was attenuated by simultaneous biting behavior. Acute immobilization stress, in increments of up to 15min, produced detectable amounts of pERK1/2 that were proportional to the interval of stress. Biting during the acute immobilization stress significantly reduced the amount of detectable pERK1/2. These results suggest that biting activity during acute stress inhibits pERK1/2 in this region of the brain. It is feasible that the neuronal cellular response to acute stress is regulated, in some part, by inhibition of pERK1/2 by biting.

Inhibitory effect of peony root extract on pentylenetetrazol-induced EEG power spectrum changes and extracellular calcium concentration changes in rat cerebral cortex

To elucidate the mechanism of anticonvulsant action of peony root and to determine the relative contributions of pure component substances, the water, water/acetone and methanol extracts of peony roots, paeoniflorin, albiflorin and pentagalloylglucose were studied in rats using the EEG power spectrum changes induced by pentylenetetrazol administration and the extracellular calcium and potassium concentration changes related to seizure activity. The water extract of peony roots, albiflorin and pentagalloylglucose given orally completely inhibited the EEG power spectrum changes as well as the extracellular calcium and potassium concentration changes related to seizure activity. The water/acetone and methanol extracts and paeoniflorin were relatively less potent. These findings suggested that the anticonvulsant action of peony roots is due primarily to albiflorin and the gallotannin fraction. Albiflorin and pentagalloylglucose appear to manifest their anticonvulsant action due to inhibition of the seizure-related decrease of extracellular calcium and consequent intracellular calcium increase.

On a neural mechanism for cortical processing of taste quality in the rat.

The responses of 31 chorda tympani fibers and 47 cortical neurons were recorded in response to 6 concentrations of NaCl, and single concentrations of sucrose, HCl, and quinine hydrochloride solutions applied to the anterior portion of the tongue in rats. The neural responses were analyzed in terms of the two hypotheses of quality coding: across-neuron response pattern and across-region response pattern notions. In a behavioral experiment, animals were given a conditioned taste aversion to one of 5 concentrations of NaCl solution by pairing it with a gastrointestinal illness caused by i.p. injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of drinking, which indicates the extent of generalization of aversion to each of the 4 basic taste stimuli. Among the two neural analyses employed for the chorda tympani and cortical units, across-region correlation coefficients for cortical neurons that were derived from the across-region response pattern theory showed the highest correlation (r = 0.89) with the behavioral suppression rates. Across-neuron correlation coefficients in the chorda tympani fibers also showed a good correlation (r = 0.81) with the behavioral data. However, the taste profile for 1.0 M NaCl in chorda tympani fibers was very similar to that for the lower concentrations of NaCl, in spite of the suggestion from the behavioral experiment and the neural analyses of cortical responses that 1.0 M NaCl has HCl and quinine components besides the NaCl component. The present result confirmed the idea that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons.

Cloning and characterization of pentylenetetrazol-related cDNA, PTZ-17

cDNAs related to pentylenetetrazol-induced bursting activity in neurons were screened by a differential hybridization method using normal and pentylenetetrazol-treated primary cultured neurons from the cerebral cortex of mice. Twenty clones of candidate cDNA with expression increased or decreased by treatment with pentylenetetrazol were obtained. One of them, PTZ-17, was sequenced. Injection of PTZ-17 derived RNA into Xenopus oocytes showed a large calcium inward current with extracellular application of pentylenetetrazol.

Effects of extrinsic autonomic inputs on expression of c-Fos immunoreactivity in myenteric neurons of the guinea pig distal colon.

c-Fos protein is a nuclear protein coded by c-fos proto-oncogene subsequent to synaptic activation of the neurons. We used immunohistochemical methods to visualize the expression of c-Fos protein in myenteric neurons of the guinea pig distal colon and examined the effects of the extrinsic autonomic inputs on the enteric circuits. No c-Fos immunoreactivity was observed in the colonic segments fixed immediately after removal from the animal body. A number of c-Fos-immunoreactive nuclei of myenteric neurons, however, appeared in all preparations that were incubated in Krebs solution in vitro (n=10). Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of spontaneous peristaltic movements (n=5). Neither the electrical stimulation (n=8) nor the severing of the pelvic nerves (n=5) changed the number of c-Fos-positive neurons. Application of clonidine, an alpha(2)-agonist, (0.1 microM) abolished the expression of c-Fos protein in all preparations (n=5), while denervation of the sympathetic fibers in the lumbar colonic and hypogastric nerves in vivo increased the number of c-Fos-positive neurons (n=5). The results indicate that the enteric circuit in the distal part of the gastrointestinal tract is under tonic inhibition by the sympathetic nervous system from the lumbar spinal cord. c-Fos immunoreactivity expressed in the colonic preparations in vivo might be the results of enhanced activation of non-nicotinic receptors after removal of the sympathetic inhibition.

Cellular Physiology of Epileptogenic Phenomena

Epilepsy is one of the most frequently occurring nervous diseases. One out of 200 persons suffers from epilepsy. Nevertheless, there is still no definite radical therapy against epilepsy. Actual therapy against epilepsy is merely the expectation of a spontaneous cure by long-term inhibition of convulsions that facilitate the next convulsions using so-called anticonvulsant drugs, even when patients are tortured with side effects. To achieve a reasonable radical therapy, it is dispensable to elucidate the process of intracellular change of normal regular firing neurons into seizure-evoking neurons; and the differences between neurons manifesting bursting activity and those showing normal regular firing. We have hitherto investigated the intracellular events during bursting activity in a single neuron. I would like to talk about our experiments on such cellular mechanisms of epileptogenic phenomena, especially intracellular events during seizure activity. I will also describe anticonvulsant effects of a herbal mixture,. TJ-960, which shows a different mechanism of action from pure chemical anticonvulsants; and finally I will give some hints for future therapy against epilepsy.

Effect of Guanidino Compounds on Hen Egg Development

It has been reported that levels of guanidinosuccinic acid,1 methylguanidine2, β-guanidinopropionic acid3 and taurocyamine in serum of uremic patients are significantly elevated compared to normal control subjects. Also, brain levels of taurocyamine and methylguanidine were found to be increaed in experimental uremia produced by bilateral urethral ligation4. Because of these results, methylguanidine, β-guanidinopropionic acid and guanidinosuccinic acid are becoming of interest as potential “uremic toxins”.

Effects of toothbrushing on brain regional activities — a fMRI study

P3-r19 Changes in cerebral blood flow during singing: preliminary fNIRS study Mone Tsukimoto 1 , Yasunori Shiono 1, Tsuyoshi Matsumoto 1, Yasuhiro Kawano 1, Yasushi Fuchigami 1, Kunio Sato 2, Yoko Hoki 1 1 Dept. of Neurophysiol, Division of Neuroscience, Mie Univ Grad School of Medicine, Tsu, Japan 2 Dept. of System Engineering, Division of Environmental Science & Technology, Mie Univ Grad School of Bioresources, Tsu, Japan

Taste preferences and activation in the association cortex in humans

Impulsivity is often expressed as aggressive behaviour. It is associated with poor self-control which can be a major portion of many diseases if it reaches pathological levels. It can be emerged in several forms such as rapid decision making, inability to tolerate a delay of enjoyment and tendency to terminate chains of responses prematurely. Tolerance to delay of reward has been proposed as self-control. We investigated the involvement of delay duration and the amount of reinforcement in a T-maze based impulsivity task. After acclimatization, rats were trained to choose between a single food pellet delivered immediately and four or eight pellets delivered after delay. The percent of animals that chose the arm baited with large reward were signified as response and evaluated compared to the development and sort of trials. The results show an enhancement of responses by enlargement in size of reward in animals. The responses were slowly declined with increasing delay time, this was significant in 10–30 s. To clarify the details more studies can be conducted by using of this animal model.

Ameliorative Effects of Japanese Herbal Medicine on Abnormalities of the Nervous System

Irritation of the trigeminal nerve provokes not only severe pain but can also lead to the Reilly syndrome (irritation syndrome). To elucidate the mechanism of the Reilly syndrome, we investigated the interaction between the trigeminal nerve and neurons in the vagus nucleus and sympathetic neurons in the lateral horn. We also examined the effect of an herbal mixture, TJ-960, on the Reilly syndrome. The neurons in the three nuclei of the vagus (ambiguous, dorsal, and solitary nuclei), neurons in the sacral parasympathetic center, and also neurons in the lateral horn showed clear evoked unit discharges produced by stimulation of the trigeminal nerve. These unit discharges showed summation effects for stimulation of the infra-alveolar, infraorbital, and lingual nerves. The spontaneous unit discharges in the above autonomic center. The irritation to the trigeminal nerve provoked extraordinary pathological discharge in the neurons in the autonomic centers showed excitatory and inhibitory modification after repetitive stimulation of the trigeminal nerve. There were also neurons unaffected by repetitive trigeminal stimulation. These three types of neurons were scattered randomly in each nucleus. An herbal mixture, TJ-960 completely suppressed the manifestations of the Reilly syndrome when administered 2 weeks before trigeminal irritation. These data indicate that there is a clear direct connection between the trigeminal nerve and neurons in the autonomic center. The irritation to the trigeminal nerve provoked extraordinary pathological discharge in the neurons in the autonomic center, and this in turn disturbed the microcirculation in various abdominal and thoracic organs and consequently provoked the Reilly syndrome. Administration of TJ-960 effectively suppressed the Reilly syndrome without any disturbances in normal nervous function.