The effect of immediate controlled forces on periodontal healing of teeth replanted after short dry time in dogs.

BACKGROUND/AIM: The extra-alveolar dry period and storage medium in which a tooth is kept prior to replantation remain critical factors affecting the survival and repair potential of the periodontal ligament in avulsed teeth. When replantation is not immediate, replacement root resorption (RRR) is the most common complication. The aim of this histological study was to evaluate the effect of immediate controlled-orthodontic forces in periodontal healing of replanted teeth in a canine model. MATERIAL AND METHODS: Sixty maxillary and mandibular premolar roots were endodontically treated in vivo and subsequently hemisected and extracted. Roots were replanted after an extraoral dry time of 20 minutes and randomly assigned to two experimental groups: Group 1: root was stabilized with a flexible and passive bracket/stainless steel wire splint for 2 weeks; Group 2: root was stabilized with a flexible bracket/NiTi wire splint activated with orthodontic elastics for 2 weeks. After 4 months, the dogs were euthanized, and all specimens were processed for histology and microscopically evaluated. RESULTS: The mean percentage of RRR for Group 2 was 3.17 compared with 12.13 in Group 1. Eighty-three percent of specimens from Group 2 exhibited similar healing to the negative control group, compared to 60.5% of the specimens from Group 1. No statistical difference was found in periodontal healing between experimental groups. CONCLUSION: Immediate application of mild and controlled orthodontic forces was not detrimental to the periodontal healing of teeth replanted after 20 minutes extraoral dry time, although no significant improvement on periodontal healing was observed.

Restoration of Physiological Expression of 5-HT6 Receptor into the Primary Cilia of Null Mutant Neurons Lengthens Both Primary Cilia and Dendrites.

5-HT6 (serotonin) receptors are promising targets for a variety of neuropsychiatric disorders and have been linked to several cellular signaling cascades. Endogenous 5-HT6 receptors are restricted to the primary neuronal cilium, a small sensory organelle stemming from the cell body that receives numerous extrasynaptic signals. Inhibition of 5-HT6 receptors decreases cilia length in primary neuronal cultures, but the signaling mechanisms involved are still unclear. Intense overexpression of exogenous 5-HT6 receptors increases the probability for receptors to localize outside the primary cilium and have been associated with changes in cilia morphology and dendritic outgrowth. In the present study, we explore the role of 5-HT6R rescue on neuronal morphology in primary neuronal cultures from 5-HT6R-KO mice, at the same time maintaining a more physiologic level of expression, wherein the receptor localizes to cilia in 80%-90% of neurons (similar to endogenous 5-HT6R localization). We found that rescue of 5-HT6R expression is sufficient to increase cilia length and dendritic outgrowth, but primarily in neurons in which the receptor is located exclusively in the primary cilia. Additionally, we found that expression of 5-HT6R mutants deficient in agonist-stimulated cAMP or without the predicted Fyn kinase binding domain maintained constitutive activity for stimulating cAMP and still increased the length of cilia, and that the proposed Fyn kinase domain was required for stimulating dendritic outgrowth. These findings highlight the complexity of 5-HT6R function and localization, particularly with the use of exogenous overexpression, and provide greater understanding and potential mechanisms for 5-HT6R drug therapies.

5-HT6 receptor blockade regulates primary cilia morphology in striatal neurons.

The 5-HT6 receptor has been implicated in a variety of cognitive processes including habitual behaviors, learning, and memory. It is found almost exclusively in the brain, is expressed abundantly in striatum, and localizes to neuronal primary cilia. Primary cilia are antenna-like, sensory organelles found on most neurons that receive both chemical and mechanical signals from other cells and the surrounding environment; however, the effect of 5-HT6 receptor function on cellular morphology has not been examined. We confirmed that 5-HT6 receptors were localized to primary cilia in wild-type (WT) but not 5-HT6 knockout (5-HT6KO) in both native mouse brain tissue and primary cultured striatal neurons then used primary neurons cultured from WT or 5-HT6KO mice to study the function of these receptors. Selective 5-HT6 antagonists reduced cilia length in neurons cultured from wild-type mice in a concentration and time-dependent manner without altering dendrites, but had no effect on cilia length in 5-HT6KO cultured neurons. Varying the expression levels of heterologously expressed 5-HT6 receptors affected the fidelity of ciliary localization in both WT and 5-HT6KO neurons; overexpression lead to increasing amounts of 5-HT6 localization outside of the cilia but did not alter cilia morphology. Introducing discrete mutations into the third cytoplasmic loop of the 5-HT6 receptor greatly reduced, but did not entirely eliminate, trafficking of the 5-HT6 receptor to primary cilia. These data suggest that blocking 5-HT6 receptor activity reduces the length of primary cilia and that mechanisms that regulate trafficking of 5-HT6 receptors to cilia are more complex than previously thought.