Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.

Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable Shank3 complexes is regulated by the binding of zinc to the C-terminal sterile-alpha-motif (SAM) domain of Shank3. Mutations in the SAM domain of Shank3 result in altered synaptic function and morphology, and disruption of zinc in synapses that express Shank3 leads to a reduction of postsynaptic proteins important for synaptic structure and function. This suggests that zinc supports the localization of postsynaptic proteins via Shank3. Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice-which lack synaptic zinc-show behavioral deficits associated with autism spectrum disorder and schizophrenia. Here we show that male and female ZnT3 KO mice have smaller dendritic spines and miniature excitatory postsynaptic current amplitudes than wildtype (WT) mice in the auditory cortex. Additionally, spine size deficits in ZnT3 KO mice are restricted to synapses that express Shank3. In WT mice, synapses that express both Shank3 and ZnT3 have larger spines compared to synapses that express Shank3 but not ZnT3. Together these findings suggest a mechanism whereby presynaptic ZnT3-dependent zinc supports postsynaptic structure and function via Shank3 in a synapse-specific manner.

Synaptic zinc potentiates AMPA receptor function in mouse auditory cortex.

Synaptic zinc signaling modulates synaptic activity and is present in specific populations of cortical neurons, suggesting that synaptic zinc contributes to the diversity of intracortical synaptic microcircuits and their functional specificity. To understand the role of zinc signaling in the cortex, we performed whole-cell patch-clamp recordings from intratelencephalic (IT)-type neurons and pyramidal tract (PT)-type neurons in layer 5 of the mouse auditory cortex during optogenetic stimulation of specific classes of presynaptic neurons. Our results show that synaptic zinc potentiates AMPA receptor (AMPAR) function in a synapse-specific manner. We performed in vivo 2-photon calcium imaging of the same classes of neurons in awake mice and found that changes in synaptic zinc can widen or sharpen the sound-frequency tuning bandwidth of IT-type neurons but only widen the tuning bandwidth of PT-type neurons. These results provide evidence for synapse- and cell-type-specific actions of synaptic zinc in the cortex.

Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis-A pilot study.

OBJECTIVES: Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA. DESIGN: Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1ß) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains. RESULTS: PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1ß levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples. CONCLUSION: Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.

Correlation of Three-Dimensional Radiologic Data with Subsequent Treatment Approach in Patients with Peri-implantitis: A Retrospective Analysis.

The purpose of this retrospective radiographic study was to evaluate and correlate the dimensions and morphology of peri-implant bone defects as determined via cone beam computed tomography (CBCT) scans with regard to the selected treatment approach. Vertical and horizontal peri-implant bone defects (mesial, distal, mesio-oral, mesiobuccal, disto-oral, distobuccal, oral, and buccal) in peri-implantitis cases were measured. Three-dimensional data and defect morphology were correlated to the treatment approach chosen (explantation versus implant retention). A total of 19 patients and 28 implants met the inclusion criteria, resulting in a sample size of 224 sites and a total of 896 measurements. The mean percent bone loss did not correlate to the type of treatment chosen (P = .1286). In contrast, when only the maximum vertical values per implant were selected, maximum percent bone loss exhibited a significant correlation to the type of treatment chosen (P = .0021). The effect of the defect morphology on the treatment strategy chosen did not show a statistically significant correlation (P = .4685). Based on the data presented, the maximum bone loss around the implant seems to be a critical factor in deciding whether or not an implant should be explanted. The use of CBCT for treatment planning in cases of peri-implantitis can offer valuable additional information but should be considered only after initial clinical examination and two-dimensional imaging.

In Vitro-Activity of Er:YAG Laser in Comparison with other Treatment Modalities on Biofilm Ablation from Implant and Tooth Surfaces.

BACKGROUND AND AIM: Bacterial biofilms play a major role in the etiology of periodontal and peri-implant diseases. The aim of the study was to evaluate the removal of bacterial biofilms and attachment of epithelial cells (EC), gingival fibroblasts (GF) and osteoblast-like cells (OC) to dentin and titanium surfaces after Er:YAG laser (Er:YAG) in comparison with other treatment methods. MATERIAL AND METHODS: Multi-species bacterial biofilms were grown on standardized dentin and titanium specimens with a sand-blasted and acid etched (SLA) surface for 3.5 d. Thereafter, the specimens were placed into artificially-created pockets. The following methods for biofilm removal were used: 1) Gracey (dentin) or titanium curettes (CUR), 2) Er:YAG, 3) photodynamic therapy (PDT) and 4) CUR with adjunctive PDT (CUR/PDT). Colony forming units (CFUs) of the remaining biofilms and attachment of EC, GF and OC were determined. Statistical analysis was performed by means of ANOVA with post-hoc LSD. RESULTS: All treatment methods decreased statistically significantly (p<0.001) total CFUs in biofilms compared with untreated dentin and titanium surfaces respectively. On dentin, Er:YAG was equally efficient as CUR and PDT but inferior to CUR/PDT (p = 0.005). On titanium, surfaces, the use of Er:YAG resulted in statistically significantly superior biofilm removal compared to the 3 other treatments (each p<0.001). Counts of attached EC, GF and OC were the lowest on untreated contaminated dentin and titanium surfaces each. After CUR/PDT higher EC counts were found on dentin (p = 0.006). On titanium, all decontamination methods statistically significantly increased (p<0.001) the counts of attached EC without differences between groups. Statistically significantly higher counts of GF (p = 0.024) and OC (p<0.001) were observed after Er:YAG decontamination compared with untreated surfaces. CONCLUSION: Ablation of subgingival biofilms and in particular decontamination of titanium implant surfaces with an Er:YAG laser seem to be a promising approach and warrants further investigations.

Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis.

OBJECTIVES: Since the peptidyl arginine deiminase of Porphyromonas gingivalis is able to citrullinate peptides and proteins, various studies have suggested the species as a possible link between periodontal disease (PD) and rheumatoid arthritis (RA). This systematic review including meta-analysis was aimed to evaluate whether differences in terms of antibody titers against P. gingivalis exist between RA patients and systemically healthy individuals with and without PD. MATERIALS AND METHODS: The following focused question was addressed: Are the antibody titers against P. gingivalis of RA patients different from systemically healthy individuals with and without PD? A systematic data search was conducted in MEDLINE and EMBASE. The collected data underwent a meta-analysis to detect statistically significant differences in terms of antibody levels between the groups. RESULTS: From 114 articles found by the search 13 articles met the inclusion criteria and provided data suitable for meta-analysis. After analyzing various levels of confinement the meta-analysis revealed a statistically significant higher antibody titer against P. gingivalis in patients suffering from RA in comparison with systemically and periodontally healthy controls (p < 0.01) and systemically healthy patients with PD (p < 0.01). CONCLUSION: The present findings indicate that RA is often accompanied by the presence of an immune response against P. gingivalis. CLINICAL RELEVANCE: The significantly higher antibody response to P. gingivalis in comparison to systemically healthy individuals supports the link between PD and RA by P. gingivalis. Screening of the regularly taken blood samples of RA patients for P. gingivalis antibodies may help to sensitize rheumatologists and RA patients for improving periodontal health.

In vitro evaluation of surface roughness, adhesion of periodontal ligament fibroblasts, and Streptococcus gordonii following root instrumentation with Gracey curettes and subsequent polishing with diamond-coated curettes.

OBJECTIVES: The objective of the study was to evaluate the efficacy of an additional usage of a diamond-coated curette on surface roughness, adhesion of periodontal ligament (PDL) fibroblasts, and of Streptococcus gordonii in vitro. MATERIALS AND METHODS: Test specimens were prepared from extracted teeth and exposed to instrumentation with conventional Gracey curettes with or without additional use of diamond-coated curettes. Surface roughness (Ra and Rz) was measured before and following treatment. In addition, the adhesion of PDL fibroblasts for 72 h and adhesion of S. gordonii ATCC 10558 for 2 h have been determined. RESULTS: Instrumentation with conventional Gracey curettes reduced surface roughness (median Ra before: 0.36 µm/after: 0.25 µm; p < 0.001; median Rz before: 2.34 µm/after: 1.61 µm; p < 0.001). The subsequent instrumentation with the diamond-coated curettes resulted in a median Ra of 0.31 µm/Rz of 2.06 µm (no significance in comparison to controls). The number of attached PDL fibroblasts did not change following scaling with Gracey curettes. The additional instrumentation with the diamond-coated curettes resulted in a two-fold increase in the number of attached PDL fibroblasts but not in the numbers of adhered bacteria. CONCLUSIONS: Treatment of root surfaces with conventional Gracey curettes followed by subsequent polishing with diamond-coated curettes may result in a root surface which provides favorable conditions for the attachment of PDL fibroblasts without enhancing microbial adhesion. CLINICAL RELEVANCE: The improved attachment of PDL fibroblasts and the limited microbial adhesion on root surfaces treated with scaling with conventional Gracey curettes followed by subsequent polishing with diamond-coated curettes may favor periodontal wound healing.