Biomedical subjects

J R Moiseiwitsch

Publications and source records attributed to J R Moiseiwitsch.

9 recordsLinked to original sources

PubMed2000

The role of serotonin and neurotransmitters during craniofacial development.

Several neurotransmitters, in particular serotonin (5-HT), have demonstrated multiple functions during early development and mid-gestational craniofacial morphogenesis. Early studies indicated that 5-HT is present in the oocyte, where it appears to function as a regulator of cell cleavage. Later, it has a significant role during gastrulation, during which there are significant areas of 5-HT uptake in the primitive streak. Subsequently, in association with neurulation, 5-HT uptake is seen in the floor plate of the developing neural tube. During neural crest formation and branchial arch formation, 5-HT has been demonstrated to facilitate cell migration and stimulate cell differentiation. During morphogenesis of the craniofacial structures, 5-HT stimulates dental development and may aid in cusp formation. All of the most commonly prescribed antidepressant drugs inhibit serotonin uptake, yet they do not appear to cause major craniofacial malformations in vivo. Given the wide spectrum of effects that 5-HT has during development, it is difficult to understand why these anti-depressants are not major teratogens. Redundancy within the system may allow receptor and uptake pathways to function normally even with lower than normal levels of circulating serotonin. Serotonin-binding proteins, that are expressed in most craniofacial regions at critical times during craniofacial development, may have a buffering capacity that maintains adequate 5-HT tissue concentrations over a wide range of 5-HT serum concentrations. Dental development appears to be particularly sensitive to even small fluctuations in concentrations of 5-HT. Therefore, it may be that children of patients who have received selective serotonergic re-uptake inhibitors (such as Prozac and Zoloft) or the less selective tricyclic anti-depressant drugs (such as Elavil) would be at a higher risk for developmental dental defects such as anodontia and hypodontia. In this review, the evidence supporting a role for 5-HT during mammalian craniofacial development is discussed. A series of models is proposed that may explain how the craniofacial effects of 5-HT are mediated.

Animals↗

PubMed1998

Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures.

Serotonin (5-HT) stimulates tooth-germ development in embryonic mouse mandibular explant cultures, but it is not clear whether this is due to a direct action on epithelial-mesenchymal interactions, or whether development was stimulated indirectly by serotonergic regulation of other morphoregulatory molecules. A calcium-binding protein, S-100beta, and the extracellular-matrix molecule, tenascin, two molecules thought to be important in craniofacial development, together with cartilage proteoglycan core protein, a marker for chondrogenesis, are modulated by serotonergic ligands in mandibular micromass cultures. Here, it was demonstrated that 5-HT stimulates expression of cartilage proteoglycan core protein, and inhibits expression of S-100beta and tenascin in mandibular explants. Further, ondansetron (Zofran), a 5-HT3 receptor antagonist, and NAN-190, a 5-HT1A antagonist, reversed the serotonergic stimulation of core protein and tooth germ development. In contrast serotonergic modulation of S-100beta and tenascin expression was not reversed by any of the 5-HT receptor antagonists tested, although the 5-HT uptake inhibitor, fluoxetine, did reverse the effect of 5-HT on S-100beta expression, as well as tooth-germ development. These results support previous work suggesting that 5-HT plays an important part in craniofacial development, especially in dentinogenesis and chondrogenesis. However, the possibility that tenascin or S-100beta mediate the effects of 5-HT on tooth-germ development is not supported. Rather, these results raise the possibility that 5-HT may exert effects directly on tooth-germ morphogenesis mediated by intracellular uptake of 5-HT and/or activation of 5-HT1A and 5-HT3 receptors.

Aggrecans↗

PubMed1998

Position of the mental foramen in a North American, white population.

UNLABELLED: Knowledge of the position of the mental foramen is important both when administering regional anesthesia and performing periapical surgery in the mandible. Although it is often possible to identify the mental foramen by palpation and radiographically, knowing the normal range of possible locations is essential. Standard anatomic texts have data collected from dried skulls, but often of unknown origin or from an ethnic group that does not represent the North American population. OBJECTIVES: This study identified the position of the mental foramen in a more representative sample of the North American population. Ethnic and gender differences were also investigated and the symmetry of location within individuals analyzed. STUDY DESIGN: Regional dissections of 105 human cadavers were carried out to identify the normal range of position of the mental foramen. The vertical and horizontal position was recorded with the two adjacent teeth used as references. If the two adjacent teeth were not present the foramen was not included in the study. RESULTS: The results indicated that the mental foramen was, on average, between the premolars, therefore not statistically different from previous studies. However, there appears to be a greater range than generally reported, which is of considerable clinical significance. Examples of dissections of unusually positioned mental foramina are given.

Anesthesia, Dental↗

PubMed1998

Nonsurgical root canal therapy treatment with apparent indications for root-end surgery.

The recent introduction of the surgical microscope to the practice of endodontics, especially for surgery, has allowed clearer visualization of the periapex during root-end resection and filling. However, despite this and other technologic advances, it has not been demonstrated that in the absence of thorough canal debridement the success rate of periapical surgery has improved over the 50% to 60% demonstrated in most long-term prognosis studies. Therefore it remains important to fully instrument and obturate the root canal system with conventional therapy before surgery is considered; this considerably improves the long-term prognosis. Each of the case reports in this article involves a situation in which conventional treatment was performed when a surgical approach might have been considered as the treatment of choice. Surgery should not be considered to be the primary treatment when root canal treatment or retreatment may be readily achieved. Indeed, the operating microscope and other technical aids will probably allow more cases to be treated and retreated conventionally that might otherwise have required surgical intervention.

Adolescent↗

PubMed1997

Regulation of gene expression in cultured embryonic mouse mandibular mesenchyme by serotonin antagonists.

During murine embryogenesis, uptake sites for the neurotransmitter serotonin (5-HT) are transiently expressed in craniofacial epithelial structures. Based on malformations produced in cultured mouse embryos exposed to uptake inhibitors or receptor ligands, we have proposed that 5-HT acts as a dose-dependent morphogenetic signal during critical periods of craniofacial development. Several 5-HT receptor subtypes are co-distributed with tenascin and the calcium binding protein S-100 beta in developing craniofacial mesenchyme. Since these molecules are thought to be important for craniofacial development, their regulation by 5-HT could mediate some of its morphogenetic actions. Mandibular mesenchyme cells, from E12 mouse embryos (plug day = E1), grown in micromass cultures were used as an in vitro model to investigate whether 5-HT regulates expression of these molecules. Immunocytochemistry revealed expression of S-100 beta, tenascin, cartilage proteoglycan core protein (a component of the cartilage matrix) and a variety of 5-HT receptors in these cultures. To block the actions of 5-HT (from serum in the culture medium), cultures were exposed to one of these selective 5-HT receptor antagonists and effects on expression were investigated using quantitative immunobinding and in situ hybridization assays. These antagonists differentially regulated expression of cartilage core protein, S-100 beta and tenascin. Antagonism of 5-HT3 receptors by Zofran or 5-HT1A receptors by NAN-190 reduced the amount of core protein, whereas antagonism of 5-HT2A-C receptors by mianserin had no significant effect. All three antagonists stimulated levels of tenascin mRNA and protein. Expression of S-100 beta mRNA and protein was inhibited by Zofran and stimulated by mianserin, whereas NAN-190 had no significant effect. The differential effects of antagonists suggest that in vivo, 5-HT could: (1) promote expression of cartilage core protein by activation of 5-HT3 or 5-HT1A receptors, (2) inhibit production of tenascin by activation of multiple receptors, (3) promote or inhibit synthesis of S-100 beta by activation of 5-HT3 or 5-HT2 receptors, respectively. These actions may be important components of the morphogenetic functions of 5-HT during craniofacial development.

Aggrecans↗

PubMed1996

Stimulation of murine tooth development in organotypic culture by the neurotransmitter serotonin.

Serotonin (5-hydroxytryptamine; 5-HT) uptake sites are transiently expressed in craniofacial epithelia and mesenchyme, including the tooth germ, during mouse embryogenesis. Based on malformations and patterns of cell proliferation and death in cultured mouse embryos exposed to 5-HT uptake inhibitors, it has been hypothesized that 5-HT acts as a dose-dependent morphogenetic signal for craniofacial development. The present study was designed to investigate the effect of 5-HT on tooth-germ formation in serum-free mandibular explant cultures prepared from embryonic day-13 (plug day = embryonic day-1) mouse embryos. In the absence of serum or a 5-HT supplement, tooth germs develop only to the bud stage in these cultures. When explants were cultured for 8 days in a defined medium supplemented with 5-HT, late bell-stage tooth germs were stimulated to develop in a dose-dependent manner. This effect was reversed by addition of the 5-HT uptake inhibitor fluoxetine. Anti-5-HT immunocytochemistry demonstrated specific uptake of 5-HT by developing tooth germ and mandibular epithelium, which could also be blocked by fluoxetine. These results suggest that 5-HT may regulate dental differentiation, and that intracellular uptake is required for this action.

Animals↗

PubMed1995

Serotonin regulates mouse cranial neural crest migration.

Serotonergic agents (uptake inhibitors, receptor ligands) cause significant craniofacial malformations in cultured mouse embryos suggesting that 5-hydroxytryptamine (serotonin) (5-HT) may be an important regulator of craniofacial development. To determine whether serotonergic regulation of cell migration might underly some of these effects, cranial neural crest (NC) explants from embryonic day 9 (E9) (plug day = E1) mouse embryos or dissociated mandibular mesenchyme cells (derived from NC) from E12 embryos were placed in a modified Boyden chamber to measure effects of serotonergic agents on cell migration. A dose-dependent effect of 5-HT on the migration of highly motile cranial NC cells was demonstrated, such that low concentrations of 5-HT stimulated migration, whereas this effect was progressively lost as the dose of 5-HT was increased. In contrast, most concentrations of 5-HT inhibited migration of less motile, mandibular mesenchyme cells. To investigate the possible involvement of specific 5-HT receptors in the stimulation of NC migration, several 5-HT subtype-selective antagonists were used to block the effects of the most stimulatory dose of 5-HT (0.01 microM). Only NAN-190 (a 5-HT1A antagonist) inhibited the effect of 5-HT, suggesting involvement of this receptor. Further evidence was obtained by using immunohistochemistry with 5-HT receptor antibodies, which revealed expression of the 5-HT1A receptor but not other subtypes by migrating NC cells in both embryos and cranial NC explants. These results suggest that by activating appropriate receptors 5-HT may regulate migration of cranial NC cells and their mesenchymal derivatives in the mouse embryo.

Animals↗

PubMed1995

Avoiding the mental foramen during periapical surgery.

Many endodontists avoid surgical procedures in proximity to the mental foramen. Although a healthy respect for regional anatomy is important, this should not be at the expense of failing to offer the most appropriate endodontic care. When correct preoperative diagnostic and surgical techniques are used, serious negative sequelae are rarely encountered. Three simple steps used during presurgical diagnosis, flap design, and surgery are presented to increase the practitioner's confidence and safety while performing mandibular periapical surgery.

Chin↗

PubMed1993

In situ localization of tenascin mRNA in developing mouse teeth.

Tenascin is a large extracellular-matrix glycoprotein found in developing connective tissue. A cDNA probe to mouse tenascin, mTN2, was used to determine the cellular origins of this molecule in the murine tooth germ by in situ hybridization. At embryonic day 19, a hybridization signal significantly greater than background was detected with mTN2 in the subodontoblastic layer of the dental mesenchyme and in the inner enamel epithelium of the enamel organ. At postnatal day 1, a signal was detected over pre-odontoblasts and the strata intermedium and externum. No tenascin mRNA was detected in odontoblasts or the stellate reticulum at either age, and hybridization in ameloblasts was not significantly greater than background at postnatal day 1. Thus, much of the tenascin found throughout developing teeth appears to be synthesized by pre-odontoblasts and the inner enamel epithelium, the two populations of cells destined to generate mineralized matrix.

3T3 Cells↗