Sachio Nagasaki

Impairment of spatial memory and changes in astroglial responsiveness following loss of molar teeth in aged SAMP8 mice

In order to evaluate the mechanism(s) responsible for senile impairment of cognitive function as a result of reduced mastication, the effects of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrous acidic protein (GFAP) and on spatial memory in young adult and aged SAMP8 mice were studied using immunohistochemical and behavioral techniques. Aged molarless mice showed a significantly reduced learning ability in a water maze test compared with age-matched control mice, while there was no difference between control and molarless young adult mice. Immunohistochemical analysis showed that the molarless condition enhanced the age-dependent increase in the density and hypertrophy of GFAP-labeled astrocytes in the CA1 region of the hippocampus. These effects increased the longer the molarless condition persisted. When the extracellular K+ concentration ([K+]o) was increased from 4 to 40 mM for hippocampal slices in vitro, the mean increase in the membrane potential was about 57 mV for fine, delicate astrocytes, the most frequently observed type of GFAP-positive cell in the young adult mice, and about 44 mV for the hypertrophic astrocytes of aged mice. However, there was no significant difference in resting membrane potential between these cell types. The data suggest that an impairment of spatial memory and changes in astroglial responsiveness occur following the loss of molar teeth in aged SAMP8 mice.

Effects of aging on lateral stability in quiet stance

Background and aims: Recent studies have demonstrated that assuming the postural corrective torque is regulated by a proportional-integralderivative (PID) controller in the anterior/posterior direction, although few studies have discussed the medial/lateral (M/L) direction through PID control. Instability in the M/L direction has been reported to be closely related with the risk of falling in the elderly. The purpose of this study is to evaluate the mechanism of postural control in the M/L direction in the elderly. Methods: The movement of a marker on the subject’s back was measured by a CMOS video camera and trunk sway speeds in the M/L direction (TSSX) were calculated as absolute values in whole time series. Using trunk sway data, we identified the gain of PID parameters (proportional gain: KP, integral gain: KI derivative gain: KD). In addition, we calculated the frequency spectrum of trunk sway using the marker locus from 0.016 to 5 Hz by fast Fourier transform. A total of 40 healthy subjects aged from 20 to 85 years old was evaluated with the PID control algorithm in a model of postural control in the M/L direction and their parameter values were estimated. Results:KP significantly increased with age, whereas KD tended to decrease. The TSSX and power ratio of medium frequency (0.2-2.0 Hz) significantly increased with age, but the power ratio of low frequency (0.02-0.2 Hz) tended to decrease. KP and KI were significantly correlated with the power ratio of medium frequency. There was a significant negative correlation between KD and TSSX. Conclusions: Our results indicate that dependence on hip and ankle stiffness, which may be controlled by proportional gain, increases with age for postural control in the M/L direction. A disability in the feedback mechanism based on velocity information for postural control, which may be associated with derivative gain, tends to increase with age but shows considerable individual variation.

Lidocaine suppresses the sodium current inEuhadra neurons which is mediated by cAMP-dependent protein phosphorylation

The action of a local anesthetic, lidocaine, in association with the cyclic AMP (cAMP)-mediated intracellular biochemical process, was examined in identified Euhadra neurons. Lidocaine dose-dependently inhibited the inward current which was elicited by dibutyryl cAMP (db-cAMP) and isobutylmethylxanthine (IBMX). This inhibitory effect was transiently reversed by the intracellular injection of a catalytic subunit of a cAMP-dependent protein kinase. The inward current elicited by db-cAMP and IBMX was abolished by Na(+)-free saline but not by Ca(2+)-free saline. The data suggest that lidocaine is not acting directly on the Na+ channel, but acts at a level proximal to the catalytic subunit of cAMP-dependent protein kinase.

Damping control of balance in the medial/lateral direction and the risk of falling in the elderly.

Aims:  A proportional–integral–derivative (PID) control has recently been used as a control algorithm of body balance. The purpose of this study was to elucidate an association of the proportional and derivative gain based on the PID control gain for balance for quiet standing with the risk factor for falls in the elderly.

Structural and functional maturation of the buccal stretch receptors in rats

Postnatal functional and structural development of the buccal stretch receptor (BSR) of rats was investigated, using electrophysiological and morphological techniques. For functional analysis, sustained discharges in response to ramp-and-hold stretches were recorded from the BSRs isolated from animals aged 10 days to 10 weeks. The threshold amplitude of stretch for a sustained discharge fell significantly between 10 days and 3 weeks, reaching adult values at 5 weeks of age, while the static sensitivity increased conspicuously between 2 and 4 weeks after birth. On the other hand, between 1 and 4 weeks of age, apparent structural changes in the BSR were observed on the number of preterminal branches in a sensory unit, the size of the varicose-like swellings along the terminal axon, the density of collagen and elastic fibers around the core structure, and the content of the sub-capsular space. From these results, we suggest that the increase in the density of the connective tissue around the core structure is associated with an enhancement in the elasticity of the BSR in the early postnatal stages, decreasing the threshold amplitude of stretch for a sustained discharge. One possible explanation for the maturation of the static sensitivity of this receptor is growth of the sensory axon terminals filled with dense mitochondria.

A novel glutamate‐mediated inhibitory mechanism linked with Ca2+/calmodulin‐dependent protein kinase II in identified Euhadra neurons

The underlying mechanism(s) of the glutamate (Glu)-induced membrane hyperpolarizing response in identified Euhadra neurons was investigated using the voltage-clamp technique, pressure injection method, and pharmacologic agents. Under voltage-clamp conditions, bath-applied Glu elicits a slow outward potassium current (Glu current) accompanied by an increase in membrane conductance whose amplitude is dose dependent. Of the agonists tested, the Glu current was mimicked only by quisqualate (QA); its potency was approximately 10 times greater than that of Glu. Typical antagonists for the ionotropic type of Glu receptors and G protein inhibitors do not block this current. The Glu current is markedly enhanced by a specific inhibitor of Ca2+/ calmodulin-dependent protein kinase II (CaM-KII), KN-62 (1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine) in a dose-dependent manner, while intracellularly injected CaM-KII suppresses the current. The potent protein kinase A inhibitors, H-8 (N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride) and H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) or the specific protein kinase C inhibitors staurosporine and K-252b had no effect on the Glu current. These results suggest the presence of a novel subtype of Glu receptor in Euhadra neurons, which may be coupled to the activation of potassium channels normally suppressed by CaM-KII.

Origin of Primary Sensory Neurons Innervating the Buccal Stretch Receptor

The primary sensory neurons innervating mechanoreceptors in oro-facial regions have their cell bodies in either the trigeminal ganglion or the mesencephalic nucleus of the trigeminal nerve. The buccal stretch receptor (BSR), a type of mechanoreceptor in the jaw of rodents, has recently been recognized as signaling the position of the mandible. The location of the primary afferent neurons innervating this receptor is unknown. To investigate the cell bodies of the BSR afferent neurons in rats, we applied wheat germ agglutinin-horseradish peroxidase (WGA-HRP) to the proximal stump of the severed nerve branch of the buccal nerve that supplied the BSR. HRP-labeled cell bodies were observed in the posterolateral portion of the ipsilateral trigeminal ganglion. None was found in the contralateral trigeminal ganglion or in the brainstem. All labeled cell bodies were oval or round and closely resembled pseudo-unipolar neurons. The mean diameter of the labeled somata ranged between 25.5 and 52.5 μm, with small (≤ 30 μm), medium (from 31 to 40 μm), and large somata (≥ 41 μm) accounting for 8.8%, 54.9%, and 36.3%, respectively. Among the myelinated nerve fibers in the branch in which WGA-HRP was applied, 78.5% terminated in the BSR and had larger fiber diameters than the rest, indicating that most of the medium and large HRP-labeled cell bodies were BSR afferents. From these results and the ontogenetic origin of this receptor, it is suggested that the BSR differentiated from the mechanoreceptors in the oral mucosa or the fascia of masticatory muscles.

1401 Decrease in the learning and memorial ability induced by reduction of masticatory movement in the senescence-accelerated mouse

1401 DECREASE IN THE LEARNING AND MEMORIAL ABILITY INDUCED BY RE DUCTION OF MASTICATORY MOVEMENT IN THE SENESCENCEACCELERATED MOUSE Dept. Physiol. Gifu Univ. Sch. Med., 40 Tsukasa-machi, Gifu 500, Japan’, Dept. Anat. Gifu Univ. Sch. Med., 40 Tsukasa-machi, Gifu 500, Japan 2, Dept. Physiol. Tokyo Dent. Col., 2-2 Masago 1 Chome, Mihama-ku, Chiba 261, Japan3, Fujita Health Univ. Sch. Med., l-98 Denrakugakubo, Kutsukake-cho, Toyo-ake-shi, Aichi 470-11, Japan4

Dynamics of QT interval variability and its circadian rhythm

The circadian rhythm of QT interval variability is still unclear, although it is known that QT interval prolongation is a predictor of sudden cardiac death. The aim of present study is to establish a dynamical model between RR interval variability and QT interval variability, and to identify its dynamical parameters in 24-hr circadian rhythms. A linear mathematical dynamical model is established between RR-interval variability and QT-interval variability. The model parameters can be identified using system identification technique. Simulated data show that the mathematical model fit well to the dynamics of QT-interval variability. Eight-young healthy subjects are recruited in the study. The results show that dynamics between RR variability and QT variability is individual-specific,and their dynamical parameters express distinct circadian rhythms. The results suggest that the circadian properties of QT interval dynamics may play a prominent role in sudden cardiac death prevention.

Dynamic relationships between R-R and Q-T intervals and its possibility for autonomic nervous function evaluation

To drive rapid thermoregulatory responses to maintain body temperature during changes in ambient temperature, thermal information from the skin ascends to the preoptic area (POA), which then sends command signals to peripheral effectors. Here, we show that a population of neurons in the dorsal part of the lateral parabrachial nucleus (LPBd) is activated by skin warming and projects directly to the POA. Mimicking skin warming, activation of rat LPBd neurons inhibited the spontaneous activity of cutaneous vasoconstrictor (CVC) component of the sural sympathetic nerve and increased tail skin temperature–responses consistent with increased body heat dissipation. Inactivation of LPBd neurons or blockade of glutamate receptors in the LPBd eliminated the skin warming-induced inhibition of the spontaneous sural CVC activity. These results indicate that neurons in the LPB mediate the afferent pathway for warm signaling from the skin to the POA that is required to defend body temperature in hot environments.