JDR JDR Most Read Articles
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mori, A.
Right arrow Articles by Matsuya, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, A.
Right arrow Articles by Matsuya, T.
J Dent Res 81(9): 598-602, 2002
© 2002 International and American Associations for Dental Research

RESEARCH REPORT
Biological

Effect of Serotonin (5-HT) on Trigeminal Rhythmic Activities Generated in in vitro Brainstem Block Preparations

A. Mori, M. Kogo*, K. Ishihama, S. Tanaka, A. Enomoto, H. Koizumi, and T. Matsuya

First Department of Oral & Maxillofacial Surgery, Osaka University, Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan;

* corresponding author, kogo{at}dent.osaka-u.ac.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We used rat isolated brainstem block preparations to analyze the functional roles of serotonin receptors in the generation of trigeminal rhythmic activities. We previously reported that trigeminal rhythmic activities could be induced by some pharmacological applications in an isolated brainstem preparation with a rostral boundary at the border between the inferior and superior colliculus, and a caudal border at the level of the rostral facial nucleus. However, the same stimulation did not induce trigeminal rhythmic activities in a whole brainstem block preparation with the same rostral boundary and a caudal border at the obex level. In the present study, both the 5-HT1A phthalimido-butyl-piperazine, and the 5-HT2C agonist, 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane, combined with N-methyl-D,L-aspartate and bicuculline, elicited trigeminal rhythmic activities in a whole brainstem block preparation. Our results suggest that serotonin has both facilitation and inhibition effects on the generation of trigeminal rhythmic activities in an isolated brainstem block preparation in vitro.

KEY WORDS: trigeminal activity • serotonin • 5-HT1A receptor • 5-HT2C receptor • brainstem block preparation


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The timing signal for rhythmic movement is generated by a certain neuronal population (central pattern generator, CPG) in the central nervous system (Lund, 1991; Nakamura and Katakura, 1995). The bursting pattern of each muscle is also regulated by the burst generator. The location of the CPG involved with rhythmic jaw movements remains unknown, though results of decerebration experiments have suggested that it resides between the midbrain and the medulla (Bremer, 1923; Dellow and Lund, 1971; Thexton et al., 1980), while another study, where cortical stimulation was used to induce rhythmic jaw muscle (RJM) activities, indicated its location to be between the rostral inferior olivary nucleus and the trigeminal motor nucleus (Chandler and Tal, 1986).

An in vitro isolated brainstem-spinal cord preparation is very helpful for analysis of the neural circuit involved with physiological motor functions, and the cellular, synaptic, and biophysical properties of respiratory and locomotor rhythms as well as those of burst-pattern-generating circuits have been well-studied (Suzue, 1984; Smith et al., 1991; Cazalets et al., 1995). Oral-motor rhythmic activities in the hypoglossal nerve have also been recorded with this preparation (Katakura and Nakamura, 1995).

In previous studies, trigeminal rhythmic activities (TRAs) and rhythmic jaw movements were induced experimentally in in vitro brainstem block preparations in neonatal rats with application of the N-methyl-D-aspartate (NMDA) receptor agonist, NMA, in conjunction with the GABA receptor antagonist, bicuculline (BIC) (Kogo et al., 1996, 1998; Tanaka et al., 1999), which demonstrated that rhythm was generated around the area of the trigeminal motor nucleus. A coronal transection caudal to the trigeminal motor nucleus was required for TRA to be induced. From our results, it was suggested that some kind of inhibitory circuit also exists.

The effects of the neurotransmitters must be analyzed if the neural mechanism included in this trigeminal circuitry is to be clarified. Our previous study demonstrated that the NMDA receptor is involved in the rhythm-generation circuit (Kogo et al., 1996). However, in TRA, the functions of other receptors have not yet been clarified with use of the above-mentioned preparation, though serotonin (5-HT) is a typical neurotransmitter whose functions have been studied, e.g., in respiration, by this method (Morin et al., 1992, 1993).

For the control of rhythmic behaviors such as cat locomotion (Forssberg and Grillner, 1973; Rossignol et al., 1998) and lamprey swimming (Harris-Warrick and Cohen, 1985), the role of 5-HT has been implicated, while an iontophoretic study suggested that it also controls trigeminal movements (Katakura and Chandler, 1990). The trigeminal nucleus receives serotonergic input and contains serotonergic receptors (Kolta et al., 1993), and serotonergic axonal contacts on trigeminal motoneurons with the medullary raphe nucleus have been reported (Li et al., 1993; Nagase et al., 1997). The 5-HT1A receptor agonist has also been shown to inhibit the spinal trigeminal nucleus (Grudt et al., 1995) as well as being involved in the depolarization of trigeminal motoneurons (Kurasawa et al., 1990). However, the function of these receptors on TRAs is still unclear.

In this study, we analyzed serotonergic modulation on trigeminal rhythm generation in an in vitro isolated brainstem-spinal cord preparation.


   MATERIALS & METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Sprague-Dawley neonatal rats (from 0 to 3 days old) were deeply anesthetized with halothane. Preparation was performed in a recording chamber filled with artificial cerebrospinal fluid (ACSF) under a dissecting microscope. The neuraxis (inferior colliculus to the C4 level) was removed and pinned down on Sylgard resin as described in our previous report (Kogo et al., 1996). Three kinds of brainstem blocks were prepared. The first was from the inferior colliculus to the level of the Y-crossing point (just caudal to the trigeminal motor nucleus) (minimum block) (Fig. 1Go) (Kogo et al., 1996), the second was from the inferior colliculus to the level caudal to the facial nucleus (medium block), and the third was from the inferior colliculus to the obex (whole block).



View larger version (26K):
[in this window]
[in a new window]
  		Figure 1. Effect of 5-HT on trigeminal rhythmic activities. (A) After a coronal transection at the Y-crossing point, BIC (10 µM) - NMA (20 µM) application induced trigeminal rhythmic activities. (B) Rhythmic trigeminal motor activity was not induced in the whole brainstem preparations by chemical application of BIC (10 µM) - NMA (20 µM), whereas it was by an application of BIC (10 µM) - NMA (20 µM) combined with 5-HT (60 µM). (C) Comparison of the effect of 5-HT (60 µM) - NMA (20 µM) - BIC (10 µM) on trigeminal activities (Vm) with that on cervical nerve (C2) activities (n = 5). Middle traces show Vm and C2 activities after application. These activities were not synchronized with each other. Upper traces: trigeminal activities (Vm). Lower traces: cervical nerve (C2) activities.

 
The temperature was maintained at 25 to 27°C (Kogo et al., 1996), and a gravity-based perfusion system maintained a constant flow of standard ACSF solution (from 0.1 to 1 mL/sec). The composition of ACSF (in mM) was as follows: NaCl, 128.0; MgSO4, 1.0; KCl, 3.0; NaH2PO4, 0.5; NaHCO3, 24.0; CaCl2, 1.5; and glucose, 30.0. It was continuously equilibrated with 95% O2-5% CO2 and buffered to pH 7.4 throughout the recording chamber. Recordings were performed under steady-state conditions, while the chamber was continuously oxygenated with the 95% O2-5% CO2 mixture.

Recording and Data Analysis
According to our previous results, a bath application of excitatory amino acid, N-methyl-D,L-aspartate (NMA), and the GABAA receptor antagonist, bicuculline (BIC), could induce TRA in a minimum block preparation, whereas it could not in a whole block preparation. In the present study, we tested the effect of 5-HT on the facilitation of TRA.

Motor output signals from the trigeminal nerve of each brainstem preparation were recorded by means of suction electrodes connected by a glass pipette, filtered at 300 Hz to 3 kHz at 3 dB, and recorded on digital audio tape. The pipette was set at the C2 or C4 ventral root. In our previous study, in the first 2 to 4 min after chemical application, an increase in baseline tonic activity and irregular discharges occurred. This was followed by rhythmic activity that lasted between 30 sec and 10 min (Kogo et al., 1996). Rhythmic activity data were acquired and then analyzed with an appropriate microcomputer equipped with data acquisition/analysis software (Maclab-8S, AD Instruments, Castle Hill, Australia). Rhythm frequency was calculated automatically by the software. Statistical analysis was done with Student’s t test and with StatView.

Chemical Stimulation
Test solutions were added directly to the static chamber (20 mL) from a stock solution at the final concentration. To analyze the effect of 5-HT, we performed bath applications of NMA combined with BIC (NMA-BIC), 5-HT combined with BIC, and 5-HT agonist or antagonist with NMA-BIC. The 5-HT agonists used were: 8-hydroxy-2 (dipropylamino) tetraline-HBr 8OH-DPAT (5-HT1A receptor) and 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) (5-HT2C receptor), while the 5-HT receptor antagonists were 1-2-methoxy-phenyl-4-4-2-phthalimido-butyl-piperazine (NAN190) (5-HT1A receptor) and methysergide (5-HT2BC, 5-ht5ABreceptor).

All experiments were reviewed and approved by the Intramural Animal Care and Use Committee of Osaka University Graduate School of Dentistry.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The bath application of NMA-BIC (20 µM-10 µM) did not induce TRA in the whole blocks; however, it was induced in the minimum blocks with a rhythm frequency of 5-8 Hz. On the other hand, an additional 5-HT (60 µM) application to NMA-BIC induced TRA in all of the whole brainstem blocks (n = 9) at a rhythm frequency of 4-7 Hz. To compare respiratory activities, we made simultaneous recordings of the trigeminal and cervical nerve activities. Trigeminal rhythmic bursting was not synchronized with C2 or C4 activities, and TRA was clearly different from respiratory activities (n = 5) (Fig. 1Go).

5-HT Receptor Agonist and Antagonist
    Whole blocks (inferior colliculus to obex)
The 5-HT1A receptor agonist 8OH-DPAT (50 µM) combined with NMA-BIC did not induce TRA (n = 6), whereas it was recorded after an application of the 5-HT1A receptor antagonist, NAN190 (20 µM) combined with NMA-BIC (n = 6). Furthermore, the 5-HT2C receptor agonist DOI (20 µM) combined with NMA-BIC induced TRA (n = 4), whereas TRA was not recognized with an application of the 5-HT2BC,5 antagonist, methysergide (50 µM), and NMA-BIC (TableGo, Fig. 2AGo).


View this table:
[in this window]
[in a new window]
  		Table. Induction of TRA
 


View larger version (47K):
[in this window]
[in a new window]
  		Figure 2. Effect of 5-HT agonist and antagonist in whole and medium blocks. (A) Application of 5-HT2C receptor agonist (DOI, 20 µM) and 5-HT1A receptor antagonist (NAN190, 20 µM) induced rhythmic trigeminal motor activity in the whole brainstem preparations, whereas application of the 5-HT2BC,5 receptor antagonist (methysergide, 50 µM) and 5-HT1A receptor agonist (8OH-DPAT, 50 µM) did not. (B) Application of the 5-HT2C receptor agonist (DOI, 20 µM) and 5-HT1A receptor antagonist (NAN190, 20 µM) induced rhythmic trigeminal motor activity in the brainstem preparations that contained the facial nucleus (medium block), whereas application of the 5-HT2BC,5 receptor antagonist (methysergide, 50 µM) and 5-HT1A receptor agonist (8OH-DPAT, 50 µM) did not. (C) A section that contained the facial nucleus (medium block) prepared after the end of an experiment. (Infra-red photograph of a sagittal section, 250 µ.)

 
    Medium blocks (inferior colliculus to caudal to facial nucleus)
When combined with NMA-BIC, 5-HT (60 µM), NAN190 (20 µm), and DOI (20 µM) each induced TRA (n = 3, 7, 8, respectively); however, it did not occur with 8OH-DPAT (50 µM) or methysergide (50 µM) combined with NMA-BIC (n = 7, 8, respectively) in the medium block preparations (Figs. 2B, 2CGo).

    Minimum blocks
When combined with NMA-BIC, 5-HT (60 µM), NAN190 (20 µM), and DOI (20 µM) each induced TRA (n = 7, 14, 14, respectively); however, TRA did not occur with 8OH-DPAT (50 µM) or methysergide (50 µM) combined with NMA-BIC (n = 8, 8, respectively) in the minimum block preparations (TableGo).

Frequency of TRA
As for the frequency of the TRA induced with NMA-BIC in the minimum blocks, each recognized in the whole blocks was significantly lower. However, significant differences were not found between the TRA frequencies in the minimum block preparations enhanced with NMA-BIC and 5-HT, or NAN, and DOI (Fig. 3Go).




View larger version (53K):
[in this window]
[in a new window]
  		Figure 3. Cycle frequency of rhythmic trigeminal motor activities in minimum and whole blocks. (A) Rhythmic trigeminal motor activity was induced by an application of 5-HT (60 µM), 5-HT2C receptor agonist (DOI, 20 µM), 5-HT1A receptor antagonist (NAN190, 20 µM), and those in combination with BIC (10 µM) - NMA (20 µM) in whole brainstem preparations. Furthermore, it was also induced by BIC (10 µM) - NMA (20 µM) stimulation alone, whereas inhibition was not recognized in the minimum preparations. (B) Bar graphs indicate the cycle frequency of rhythmic trigeminal motor activities in the minimum and whole brainstem preparations as induced by 5-HT (60 µM) and those related agents (DOI, 20 µM; NAN190, 20 µM) with BIC (10 µM) - NMA (20 µM), respectively. Control: Cycle frequency of trigeminal rhythmic activities induced by BIC-NMA in the minimum brainstem blocks. In the whole brainstem, the rhythm induced by 5-HT and related agents was slower than in the control, whereas when these were applied to the minimum brainstem preparations, the rhythm was not significantly different from that of the control. *: significantly different from control (p < 0.01). Whole block: 5-HT (n = 9), DOI (n = 4), NAN190 (n = 6). Minimum block: Control (n = 8), 5-HT (n = 7), DOI (n = 14), NAN190 (n = 14).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present study revealed that enhancement and inhibition of the trigeminal circuit occurred with 5-HT. The 5-HT2C receptor agonist showed enhancement in the whole blocks, while the 5-HT1A receptor was involved in the inhibitory circuit.

Inhibition
Our previous studies showed that an NMA-BIC application induced TRA and rhythmic jaw movements in minimum block preparations. On the other hand, we also found that an NMA-BIC application could not induce them in a whole brainstem blocks (Kogo et al., 1996, 1998; Tanaka et al., 1999). The inhibitory circuit is likely located between the caudal end of the trigeminal motor nucleus and the caudal end of the facial nucleus (Tanaka et al., 1999). In the present study, an additional application of the 5-HT1A receptor antagonist NAN190 to NMA-BIC stimulated TRA that was induced in whole and medium blocks; however, it showed no such effect in the minimum blocks. Further, NAN190 blocked tonic inhibition in the whole and medium block preparations. Therefore, it is likely that the 5-HT1A receptor has an effect on the inhibitory circuit located caudal to the trigeminal motor nucleus.

Facilitation
DOI has been shown to have an agonistic action on the 5HT2C receptor in the central nervous system (Saxena, 1995). In our experiment, DOI combined with BIC-NMA induced TRA in the whole and medium blocks, whereas it did not show any effect on rhythm frequency. Thus, it is likely that the effective site of DOI is not the CPG, but rather the burst generator, which controls the burst pattern of each muscle.

A previous study demonstrated a relationship between 5-HT and trigeminal activities, showing that trigeminal motoneurons are contacted by a large number of 5-HT-immunoreactive boutons (Nagase et al., 1997). A micro-injection of 5-HT into the trigeminal motor nucleus facilitated jaw reflex (Ribeiro-do-Valle et al., 1991), and an iontophoretic application of 5-HT enhanced glutamate-induced trigeminal discharges (Katakura and Chandler, 1990; Kurasawa et al., 1990). These results support our present findings of enhancement and those of other reports that have suggested such an inhibition. The jaw-opening reflex was found to be suppressed by raphe stimulation (Sessle and Hu, 1981), and serial sectioning of the brainstem suggested the location of the inhibitory circuit to be around the level of the facial nucleus (Tanaka et al., 1999). In the present study, application of the 5HT1A antagonist blocked the inhibition of TRA. It is possible that raphe-trigeminal serotonergic pathways (Li et al., 1993) around the level of the facial nucleus are related to this tonic inhibition of TRA via the 5HT1A receptor.

Effect on the CPG
Our previous results suggested that the location of the CPG of TRA is very close to the trigeminal motor nucleus (Tanaka et al., 1999), though we could not distinguish its raw activities in our experiments. In the present study, we attempted to estimate the effect of 5HT on rhythm frequency; however, significant frequency changes were not found with an additional application of 5-HT, DOI, or NAN190 to NMA-BIC-stimulated block preparations. Thus, under the present experimental conditions, it is likely that 5-HT has no effect on the CPG, but rather on the burst generator.


   ACKNOWLEDGMENTS
 
This work was supported by Grants-in-Aid for Scientific Research, A-10307050 and B-09832006, from the Ministry of Education, Science and Culture of Japan. The work is based on a thesis submitted to the graduate school faculty of Osaka University, in partial fulfillment of the requirements for a PhD degree.

Received March 16, 2001; Last revision April 12, 2002; Accepted July 8, 2002


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Bremer F (1923). Physiologie nerveuse de la mastication chez le chat et le lapin. Reflexes de mastication. Reponses masticatrices corticales et centre cortical du gout. Arch Int Phisiol 21:308–352.

Cazalets JR, Borde M, Clarac F (1995). Localization and organization of the central pattern generator for hindlimb locomotion in newborn rat. J Neurosci 15:4943–4951.[Abstract]

Chandler SH, Tal M (1986). The effects of brain stem transections on the neuronal networks responsible for rhythmical jaw muscle activity in the guinea pig. J Neurosci 6:1831–1842.[Abstract]

Dellow PG, Lund JP (1971). Evidence for central timing of rhythmical mastication. J Physiol 215:1–13.

Forssberg H, Grillner S (1973). The locomotion of the acute spinal cat injected with clonidine i.v. Brain Res 50:184–186.[Medline]

Grudt TJ, Williams JT, Travagli RA (1995). Inhibition by 5-hydroxytryptamine and noradrenaline in substantia gelatinosa of guinea-pig spinal trigeminal nucleus. J Physiol 485(Pt1):113–120.[Medline]

Harris-Warrick RM, Cohen AH (1985) Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord. J Exp Biol 116:27–46.[Abstract/Free Full Text]

Katakura N, Chandler SH (1990). An iontophoretic analysis of the pharmacologic mechanisms responsible for trigeminal motoneuronal discharge during masticatory-like activity in the guinea pig. J Neurophysiol 63:356–369.[Abstract/Free Full Text]

Katakura N, Jia L, Nakamura Y (1995). NMDA-induced rhythmical activity in XII nerve of isolated CNS from newborn rats. Neuroreport 6:601–604.[Medline]

Kogo M, Funk GD, Chandler SH (1996). Rhythmical oral-motor activity recorded in an in vitro brainstem preparation. Somatosens Mot Res 13:39–48.[Medline]

Kogo M, Tanaka S, Chandler SH, Matsuya T (1998). Examination of the relationships between jaw opener and closer rhythmical muscle activity in an in vitro brainstem jaw-attached preparation. Somatosens Mot Res 15:200–210.[Medline]

Kolta A, Dubuc R, Lund JP (1993). An immunocytochemical and autoradiographic investigation of the serotoninergic innervation of trigeminal mesencephalic and motor nuclei in the rabbit. Neuroscience 53:1113–1126.[Medline]

Kurasawa I, Toda K, Nakamura Y (1990). Non-reciprocal facilitation of trigeminal motoneurons innervating jaw-closing and jaw-opening muscles induced by iontophoretic application of serotonin in the guinea pig. Brain Res 515:126–134.[Medline]

Li YQ, Takada M, Mizuno N (1993). The sites of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossal nuclei in the rat. Neurosci Res 17:307–313.[Medline]

Lund JP (1991). Mastication and its control by the brain stem. Crit Rev Oral Biol Med 2:33–64.[Abstract/Free Full Text]

Morin D, Monteau R, Hilaire G (1992). Compared effects of serotonin on cervical and hypoglossal inspiratory activities: an in vitro study in the newborn rat. J Physiol 451:605–629.[Abstract/Free Full Text]

Morin D (1993). Compared effects of serotonin on the inspiratory activity of glossopharyngeal, vagal, hypoglossal and cervical motoneurons in neonatal rat brain stem-spinal cord preparations. Neurosci Lett 160:61–64.[Medline]

Nagase Y, Moritani M, Nakagawa S, Yoshida A, Takemura M, Zhang LF, et al. (1997). Serotonergic axonal contacts on identified cat trigeminal motoneurons and their correlation with medullary raphe nucleus stimulation. J Comp Neurol 384:443–455.[Medline]

Nakamura Y, Katakura N (1995). Generation of masticatory rhythm in the brainstem. Neurosci Res 23:1–19.[Medline]

Ribeiro-do-Valle LE, Metzler CW, Jacobs BL (1991). Facilitation of masseter EMG and masseteric (jaw-closure) reflex by serotonin in behaving cats. Brain Res 550:197–204.[Medline]

Rossignol S, Chau C, Brustein E, Giroux N, Bouyer L, Barbeau H, et al. (1998). Pharmacological activation and modulation of the central pattern generator for locomotion in the cat. Ann NY Acad Sci 860:346–359.[Medline]

Saxena PR (1995). Serotonin receptors: subtypes, functional responses and therapeutic relevance. Pharmacol Ther 66:339–368.[Medline]

Sessle BJ, Hu JW (1981). Raphe-induced suppression of the jaw-opening reflex and single neurons in trigeminal subnucleus oralis, and influence of naloxone and subnucleus caudalis. Pain 10:19–36.[Medline]

Smith JC, Ellenberger HH, Ballanyi K, Richter DW, Feldman JL (1991). Pre-Botzinger complex: a brainstem region that may generate respiratory rhythm in mammals. Science 254:726–729.[Abstract/Free Full Text]

Suzue T (1984). Respiratory rhythm generation in the in vitro brain stem-spinal cord preparation of the neonatal rat. J Physiol 354:173–183.[Abstract/Free Full Text]

Tanaka S, Kogo M, Chandler SH, Matsuya T (1999). Localization of oral-motor rhythmogenic circuits in the isolated rat brainstem preparation. Brain Res 821:190–199.[Medline]

Thexton AJ, Griffiths C, McGarrick J (1980). Evidence for peripheral activation of the trigeminal rhythm generator in the decerebrate rat, obtained by Fourier analysis of conditioning testing curves. Arch Oral Biol 25:491–494.[Medline]




This article has been cited by other articles:


Home page
 J. Dent. Res.Home page
H. Koizumi, K. Nomura, K. Ishihama, T. Yamanishi, A. Enomoto, and M. Kogo
Inhibition of Trigeminal Respiratory Activity by Suckling
J. Dent. Res., November 1, 2007; 86(11): 1073 - 1077.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mori, A.
Right arrow Articles by Matsuya, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, A.
Right arrow Articles by Matsuya, T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
IADR Journals Advances in Dental Research ®
Journal of Dental Research ® Critical Reviews (1990-2004)