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Partial edentulism, characterized by the congenital absence of six or more permanent teeth (oligodontia), excluding the third molars, manifests with variable maxillofacial skeletal morphologies and occlusions, depending on the site and number of missing teeth, complicating treatment planning for occlusion and gain of function. Herein, we describe the case of a patient with seven non-syndromic congenitally missing permanent teeth (four in the maxillary and three in the mandibular dentition, excluding the third molars), who underwent orthodontic treatment, restorative procedures, and long-term follow-up for six years. The patient was an 18-year-old man presenting with a chief complaint of congenital absence of some permanent teeth and dental malalignment on the first visit. The mandibular right central incisor, bilateral mandibular second premolars, bilateral maxillary lateral incisors, and bilateral maxillary canines were congenitally absent, while the deciduous maxillary lateral incisors, maxillary canines, and mandibular second molars were over-retained bilaterally. Since the persisting deciduous teeth were remarkably well preserved, the patient was willing to retain them as far as possible; thus, we chose orthodontic and restorative treatment to preserve the deciduous teeth. Occlusion was established after the initiation of dynamic orthodontic treatment; restorative treatment with resin-based materials was performed for the bilateral maxillary deciduous incisors, bilateral maxillary deciduous canines, and bilateral mandibular second primary molars after bracket removal, and the retention phase of orthodontic treatment was initiated. At present, six years after establishing retention, the patient exhibits a good occlusal relationship. It is difficult to achieve complete space closure using orthodontic treatment alone in cases with six or more congenitally missing permanent teeth. In addition to considerations for age, esthetic issues due to missing permanent teeth, and maxillofacial skeletal morphology, it is necessary to preserve the deciduous teeth as much as possible and ensure multidisciplinary medical cooperation, including the transition to prosthodontic treatment during long-term follow-up.
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Reactive oxygen species (ROS) induce oxidative stress in cells and are associated with various diseases, including autoimmune diseases. Ergothioneine (EGT) is a natural amino acid derivative derived from the ergot fungus and has been reported to exhibit an effective antioxidant function in many models of oxidative stress-related diseases. Recently, mutations in OCTN1, a membrane transporter of EGT, have been reported to be associated with rheumatoid arthritis. Therefore, we investigated the chondrocyte-protective function of EGT using a model of oxidative stress-induced injury of chondrocytes by hydrogen peroxide (H2O2). Human chondrocytes were subjected to oxidative stress induced by H2O2 treatment, and cell viability, the activity of lactate dehydrogenase (LDH) released into the medium, dead cell ratio, intracellular ROS production, and mitochondrial morphology were assessed. EGT improved chondrocyte viability and LDH activity in the medium and strongly suppressed the dead cell ratio. EGT also exerted protective effects on intracellular ROS production and mitochondrial morphology. These results provide evidence to support the protective effects of EGT on chondrocytes induced by oxidative stress.
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PURPOSE: Laser irradiation activates a range of cellular processes in the periodontal components and promotes tissue repair. However, its effect on osteogenic differentiation of human cementoblast lineage cells remains unclear. This study aimed to examine the effects of high-frequency semiconductor laser irradiation on the osteogenic differentiation of human cementoblast lineage (HCEM) cells. METHODS: HCEM cells were cultured to reach 80% confluence and irradiated with a gallium-aluminum-arsenide (Ga-Al-As) semiconductor laser with a pulse width of 200 ns and wavelength of 910 at a dose of 0-2.0 J/cm2. The outcomes were assessed by analyzing the mRNA levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and type I collagen (COLL1) using real-time polymerase chain reaction (PCR) analysis 24 h after laser irradiation. Cell mineralization was evaluated using ALP activity, calcium deposition, and Alizarin Red staining. RESULTS: The laser-irradiated HCEM cells showed significantly enhanced gene expression levels of ALP, RUNX2, and COLL1 as well as ALP activity and calcium concentration in the culture medium compared with the non-irradiated cells. In addition, enhanced calcification deposits were confirmed in the laser-irradiated group compared with the non-irradiated group at 21 and 28 days after the induction of osteogenic differentiation. CONCLUSION: High-frequency semiconductor laser irradiation enhances the osteogenic differentiation potential of cultured HCEM cells, underscoring its potential utility for periodontal tissue regeneration.
Subject(s)
Cell Differentiation , Dental Cementum , Lasers, Semiconductor , Osteogenesis , Humans , Lasers, Semiconductor/therapeutic use , Cell Differentiation/radiation effects , Osteogenesis/radiation effects , Dental Cementum/radiation effects , Dental Cementum/cytology , Alkaline Phosphatase/metabolism , Cells, Cultured , Low-Level Light Therapy/methods , Core Binding Factor Alpha 1 Subunit/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Collagen Type I/genetics , Collagen Type I/metabolismABSTRACT
The thalamic reticular nucleus (TRN) is crucial for the modulation of sleep-related oscillations. The caudal and rostral subpopulations of the TRN exert diverse activities, which arise from their interconnectivity with all thalamic nuclei, as well as other brain regions. Despite the recent characterization of the functional and genetic heterogeneity of the TRN, the implications of this heterogeneity for sleep regulation have not been assessed. Here, using a combination of optogenetics and electrophysiology in C57BL/6 mice, we demonstrate that caudal and rostral TRN modulations are associated with changes in cortical alpha and delta oscillations and have distinct effects on sleep stability. Tonic silencing of the rostral TRN elongates sleep episodes, while tonic silencing of the caudal TRN fragments sleep. Overall, we show evidence of distinct roles exerted by the rostral and caudal TRN in sleep regulation and oscillatory activity.
Subject(s)
Sleep , Thalamic Nuclei , Mice , Animals , Mice, Inbred C57BL , Thalamic Nuclei/physiology , Sleep/physiology , Electrophysiological PhenomenaABSTRACT
OBJECTIVE: Root resorption may occur during orthodontic treatment. Herein, we investigated the effect of a culture supernatant of stem cells derived from human exfoliated deciduous teeth on root resorption. DESIGN: Twelve 8-week-old male Sprague-Dawley rats were used, and their maxillary first molars were pulled with excessive orthodontic force to induce root resorption. On days 1 and 7 after traction initiation, stem cells derived from human exfoliated deciduous teeth and alpha minimum essential medium (control group) were administered. After 14 days, the maxillary bone was evaluated for tooth movement. The expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 was evaluated on the compression side and tension side. RESULTS: No significant difference in tooth movement was observed between the two groups. Root resorption decreased in the group administered the culture supernatant compared with in the control. Immunohistochemical staining revealed increased osteoprotegerin expression and decreased receptor activators for nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6, and interleukin 17 on the compression side and tension side. CONCLUSIONS: Administration of stem cells derived from human exfoliated deciduous teeth affected the expression of osteoprotegerin, receptor activator of nuclear factor κB ligand, tumor necrosis factor α, interleukin 1ß, interleukin 6 and interleukin 17; hence, these stem cells may inhibit root resorption by regulating their expression.
Subject(s)
Root Resorption , Rats , Humans , Male , Animals , Root Resorption/metabolism , Osteoprotegerin/metabolism , Interleukin-17/metabolism , Tumor Necrosis Factor-alpha/metabolism , Osteoclasts , Interleukin-6/metabolism , RANK Ligand/metabolism , Interleukin-1beta/metabolism , Rats, Sprague-Dawley , Stem Cells/metabolism , Tooth, Deciduous , Tooth Movement TechniquesABSTRACT
Fiber photometry is an optical method to monitor fluorescent signals using a fiber optic cannula. Over the past two decades, together with the development of various genetically encoded biosensors, it has been applied to investigate various types of activity in the central nervous system. This includes not only type-specific neuronal population activity, but also non-neuronal activity and neurotransmitter/neuropeptide signals in awake, freely behaving animals. In this perspective, we summarize the recent development of this technique. After describing common technical pitfalls, we discuss future directions of this powerful approach for investigating brain function and dysfunction.
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Accurately and quantitatively describing mouse behavior is an important area. Although advances in machine learning have made it possible to track their behaviors accurately, reliable classification of behavioral sequences or syllables remains a challenge. In this study, we present a novel machine learning approach, called SaLSa (a combination of semi-automatic labeling and long short-term memory-based classification), to classify behavioral syllables of mice exploring an open field. This approach consists of two major steps. First, after tracking multiple body parts, spatial and temporal features of their egocentric coordinates are extracted. A fully automated unsupervised process identifies candidates for behavioral syllables, followed by manual labeling of behavioral syllables using a graphical user interface (GUI). Second, a long short-term memory (LSTM) classifier is trained with the labeled data. We found that the classification performance was marked over 97%. It provides a performance equivalent to a state-of-the-art model while classifying some of the syllables. We applied this approach to examine how hyperactivity in a mouse model of Alzheimer's disease develops with age. When the proportion of each behavioral syllable was compared between genotypes and sexes, we found that the characteristic hyperlocomotion of female Alzheimer's disease mice emerges between four and eight months. In contrast, age-related reduction in rearing is common regardless of genotype and sex. Overall, SaLSa enables detailed characterization of mouse behavior.
Subject(s)
Alzheimer Disease , Mice , Female , Animals , Memory, Short-Term , Memory, Long-TermABSTRACT
Introduction: A variety of laser treatments have been applied in numerous medical fields. In dentistry, laser treatments are used for caries, root canals, and periodontal disease, as well as surgical resection. Numerous reports have recently been published on the use of lasers for bone regeneration. If laser irradiation is found to promote the activation of bone metabolism, it might also be effective for periodontal treatment, peri-implantitis, and bone regeneration. Therefore, the present in vitro study aimed to elucidate the mechanisms underlying the effects of erbium-doped yttrium aluminum garnet (Er: YAG) laser irradiation on the bone using osteoblast-like cells. Methods: Osteoblast-like Saos 2 cells (5.0×104 cells) were seeded in 24-well plates. 24 hours after being seeded, the cells were subjected to 0.3 W, 0.6 W, and 2.0 W Er: YAG laser irradiation and then allowed to recover for 48 hours. The expression levels of bone metabolism-related factors alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteoprotegerin (OPG) were then evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Results: Saos 2 cells subjected to Er: YAG laser irradiation at 0.3 W, 0.6 W, and 2.0 W showed normal growth. When the Er: YAG laser irradiation and control groups were compared after 48 hours, increases were observed in ALP, BSP, and OPG gene and protein expression in the 2.0 W group. Similar results were obtained in the western blot analysis. Conclusion: These findings suggest that the Er: YAG laser irradiation of osteoblast-like cells is effective for activating bone metabolism factors.
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Ponto-geniculo-occipital or pontine (P) waves have long been recognized as an electrophysiological signature of rapid eye movement (REM) sleep. However, P-waves can be observed not just during REM sleep, but also during non-REM (NREM) sleep. Recent studies have uncovered that P-waves are functionally coupled with hippocampal sharp wave ripples (SWRs) during NREM sleep. However, it remains unclear to what extent P-waves during NREM sleep share their characteristics with P-waves during REM sleep and how the functional coupling to P-waves modulates SWRs. Here, we address these issues by performing multiple types of electrophysiological recordings and fiber photometry in both sexes of mice. P-waves during NREM sleep share their waveform shapes and local neural ensemble dynamics at a short (~100 milliseconds) timescale with their REM sleep counterparts. However, the dynamics of mesopontine cholinergic neurons are distinct at a longer (~10 seconds) timescale: although P-waves are accompanied by cholinergic transients, the cholinergic tone gradually reduces before P-wave genesis during NREM sleep. While P-waves are coupled to hippocampal theta rhythms during REM sleep, P-waves during NREM sleep are accompanied by a rapid reduction in hippocampal ripple power. SWRs coupled with P-waves are short-lived and hippocampal neural firing is also reduced after P-waves. These results demonstrate that P-waves are part of coordinated sleep-related activity by functionally coupling with hippocampal ensembles in a state-dependent manner.
Subject(s)
Eye Movements , Occipital Lobe , Male , Female , Animals , Mice , Occipital Lobe/physiology , Geniculate Bodies/physiology , Sleep/physiology , Hippocampus/physiology , Pons/physiologyABSTRACT
High-frequency near-infrared (NIR) semiconductor laser-irradiation has an unclear effect on nociception in the compressed lateral periodontal ligament region, a peripheral nerve region. This study aimed to investigate the effects of NIR semiconductor laser irradiation, with a power of 120 J, on inflammatory pain markers and neuropeptides induced in the compressed lateral periodontal ligament area during ETM. A NIR semiconductor laser [910 nm wavelength, 45 W maximum output power, 300 mW average output power, 30 kHz frequency, and 200 ns pulse width (Lumix 2; Fisioline, Verduno, Italy)] was used. A nickel-titanium closed coil that generated a 50-g force was applied to the maxillary left-side first molars and incisors in 7-week-old Sprague-Dawley (280-300 g) rats to induce experimental tooth movement (ETM) for 24 h. Ten rats were divided into two groups (ETM + laser, n = 5; ETM, n = 5). The right side of the ETM group (i.e., the side without induced ETM) was evaluated as the untreated group. We performed immunofluorescent histochemistry analysis to quantify the interleukin (IL)-1ß, cyclooxygenase-2 (COX2), prostaglandin E2 (PGE2), and neuropeptide [calcitonin gene-related peptide (CGRP)] expression in the compressed region of the periodontal tissue. Post-hoc Tukey-Kramer tests were used to compare the groups. Compared with the ETM group, the ETM + laser group showed significant suppression in IL-1ß (176.2 ± 12.3 vs. 310.8 ± 29.5; P < 0.01), PGE2 (104.4 ± 14.34 vs. 329.6 ± 36.52; P < 0.01), and CGRP (36.8 ± 4.88 vs. 78.0 ± 7.13; P < 0.01) expression. High-frequency NIR semiconductor laser irradiation exerts significant effects on ETM-induced inflammation. High-frequency NIR semiconductor laser irradiation can reduce periodontal inflammation during orthodontic tooth movement.
Subject(s)
Calcitonin Gene-Related Peptide , Periodontal Ligament , Rats , Animals , Rats, Sprague-Dawley , Lasers, Semiconductor/therapeutic use , Tooth Movement Techniques , Dinoprostone , Pain/radiotherapy , Infrared RaysABSTRACT
Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000-10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.
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In this study, we assessed the effects of human deciduous dental pulp-derived mesenchymal stem cell-derived conditioned medium (SHED-CM) on the properties of various cell types. The effects of vascular endothelial growth factor (VEGF) in SHED-CM on the luminal architecture, proliferative ability, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) were determined. We also investigated the effects of SHED-CM on the proliferation of human-bone-marrow mesenchymal stem cells (hBMSCs) and mouse calvarial osteoblastic cells (MC3T3-E1) as well as the expression of ALP, OCN, and RUNX2. The protein levels of ALP were examined using Western blot analysis. VEGF blockade in SHED-CM suppressed the proliferative ability and angiogenic potential of HUVECs, indicating that VEGF in SHED-CM contributes to angiogenesis. The culturing of hBMSCs and MC3T3-E1 cells with SHED-CM accelerated cell growth and enhanced mRNA expression of bone differentiation markers. The addition of SHED-CM enhanced ALP protein expression in hBMSCs and MT3T3-E1 cells compared with that of the 0% FBS group. Furthermore, SHED-CM promoted the metabolism of HUVECs, MC3T3-E1 cells, and hBMSCs. These findings indicate the potential benefits of SHED-CM in bone tissue regeneration.
Subject(s)
Culture Media, Conditioned , Dental Pulp , Human Umbilical Vein Endothelial Cells , Mesenchymal Stem Cells , Osteoblasts , Tooth, Deciduous , Animals , Humans , Mice , Core Binding Factor Alpha 1 Subunit/metabolism , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Dental Pulp/cytology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Mesenchymal Stem Cells/metabolism , Osteoblasts/drug effects , Osteoblasts/metabolism , RNA, Messenger/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tooth, Deciduous/cytologyABSTRACT
The objective of this study was to clarify the efficiency of a combination of stem cells from human deciduous teeth and carbonate apatite in bone regeneration of calvarial defects. Immunodeficient mice (n = 5 for each group/4 groups) with artificial calvarial bone defects (5 mm in diameter) were developed, and stem cells from human deciduous teeth (SHEDs) and carbonate hydroxyapatite (CAP) granules were transplanted with an atelocollagen sponge as a scaffold. A 3D analysis using microcomputed tomography, and 12 weeks after transplantation, histological and immunohistochemical evaluations of markers of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and cluster of differentiation (CD) 31 were performed. In the 3D analysis, regenerated bone formation was observed in SHEDs and CAP, with the combination of SHEDs and CAP showing significantly greater bone regeneration than that in the other groups. Histological and immunohistochemical evaluations showed that combining SHEDs and CAP enhanced the expression of BMP-2, VEGF, and CD31, and promoted bone regeneration. This study demonstrates that the combination of SHEDs and CAP transplantation may be a promising tool for bone regeneration in alveolar defects.
Subject(s)
Durapatite , Vascular Endothelial Growth Factor A , Animals , Bone Morphogenetic Protein 2/metabolism , Bone Regeneration , Carbonates , Durapatite/pharmacology , Humans , Mice , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Stem Cells/metabolism , Tooth, Deciduous , Vascular Endothelial Growth Factor A/metabolism , X-Ray MicrotomographyABSTRACT
Discomfort and dull pain are known side effects of orthodontic treatment. Pain is expected to be reduced by near-infrared (NIR) lasers; however, the mechanism underlying effects of short-pulse NIR lasers in the oral and maxillofacial area remains unclear. This study aimed to examine the effects of high-frequency NIR diode laser irradiation on pain during experimental tooth movement (ETM) on 120 J. NIR laser with 910 nm wavelength, 45 W maximum output power, 300 mW average output power, and 200 ns pulse width (Lumix 2; (Lumix 2; Fisioline, Verduno CN, Italy) was used for the experiment. A nickel-titanium-closed coil was used to apply a 50-gf force between the maxillary left-side first molar and incisor in 7-week-old Sprague-Dawley rats (280-300 g) to induce ETM. We measured facial-grooming frequency and vacuous chewing movement (VCM) period between laser-irradiation and ETM groups. We performed immunofluorescent histochemistry analysis to quantify levels of Iba-1, astrocytes, and c-fos protein-like immunoreactivity (Fos-IR) in the trigeminal spinal nucleus caudalis (Vc). Compared with the ETM group, the laser irradiation group had significantly decreased facial-grooming frequency (P = 0.0036), VCM period (P = 0.043), Fos-IR (P = 0.0028), Iba-1 levels (P = 0.0069), and glial fibrillary acidic protein (GFAP) levels (P = 0.0071). High-frequency NIR diode laser irradiation appears to have significant analgesic effects on ETM-induced pain, which involve inhibiting neuronal activity, microglia, and astrocytes, and it inhibits c-fos, Iba-1, and GFAP expression, reducing ETM-induced pain in rats. High-frequency NIR diode laser application could be applied to reduce pain during orthodontic tooth movement.
Subject(s)
Laser Therapy , Pain Management , Pain, Procedural , Tooth Movement Techniques , Animals , Incisor , Infrared Rays/therapeutic use , Lasers, Semiconductor/therapeutic use , Orthodontics, Corrective/adverse effects , Orthodontics, Corrective/methods , Pain/etiology , Pain/radiotherapy , Pain Management/methods , Pain, Procedural/etiology , Pain, Procedural/radiotherapy , Proto-Oncogene Proteins c-fos , Rats , Rats, Sprague-Dawley , Tooth Movement Techniques/adverse effects , Tooth Movement Techniques/methodsABSTRACT
BACKGROUND/PURPOSE: Baicalin, a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi, mediates bone metabolism, and recent studies have revealed that it has cell signaling properties. However, its biological functions in cementoblasts still remain unclear. This study therefore aimed to investigate the effects of baicalin on bone resorption markers, including osteoprotegerin (OPG) and receptor activator of nuclear factor-κß ligand (RANKL), in human cementoblast-lineage cells, as well as their proliferation ability. MATERIALS AND METHODS: Human cementoblast cell line (HCEM) cells were cultured and treated with 0, 0.01, 0.1, or 1 µM of baicalin. The proliferative capacity of cultured HCEM cells was analyzed using bromodeoxyuridine immunoassay and cell counting. The baicalin effect on OPG and RANKL expression was determined using quantitative polymerase chain reaction (qPCR) and western blotting. Furthermore, OPG expression was measured in 1 µM baicalin-treated HCEM cells in the presence or absence of the Wnt signaling pathway inhibitor, Dickkopf (Dkk)-1, using qPCR and western blotting. RESULTS: The addition of 0.01, 0.1, and 1 µM of baicalin did not significantly change the proliferative capacity of cultured HCEM cells. Compared with the non-supplemented group, baicalin increased and suppressed OPG and RANKL gene and protein expression, respectively, in a concentration-dependent manner. OPG mRNA and protein expression levels were increased by 1 µM baicalin, which was suppressed by Dkk-1 addition. CONCLUSION: Baicalin enhanced OPG expression in HCEM cells through the Wnt/beta-catenin signaling pathway, which could contribute to periodontal tissue regeneration.
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AIMS: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. METHODS: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. RESULTS: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19-1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23-1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48-1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97-1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13-2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17-1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88-1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68-1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85-1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0-1.44) and (OR: 1.22, 95% CI 0.75-2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82-1.58), Z-drugs (OR: 1.29, 95% CI 0.78-2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91-2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23-3.39). CONCLUSIONS: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.
Subject(s)
Dementia , Hypnotics and Sedatives , Antidepressive Agents/therapeutic use , Benzodiazepines/adverse effects , Dementia/chemically induced , Dementia/drug therapy , Dementia/epidemiology , Humans , Hypnotics and Sedatives/adverse effects , Odds RatioABSTRACT
Osteoarthritis (OA) and rheumatoid arthritis (RA) are common inflammation-associated cartilage degenerative diseases. Recent studies have shown that low-level diode laser treatment can reduce inflammatory cytokine expressions in cartilage. We recently reported that high-frequency low-level diode laser irradiation attenuates matrix metalloproteinases (MMPs) expression in human primary chondrocytes. However, the molecular mechanism underlying the effect of high-frequency low-level diode laser on chondrocytes remains unclear. Therefore, we aimed to elucidate the effect of high-frequency low-level diode laser irradiation on inflammatory cytokine expression in human primary chondrocytes. Normal human articular chondrocytes were treated with recombinant interleukin-1 beta (IL-1ß) for 30 min or 24 h and irradiated with a high-frequency NIR diode laser at 8 J/cm2. The expression of IL-1ß, interleukin-6, and tumor necrosis factor-alpha was assessed using western blot analysis. To evaluate the nuclear factor-kappa B (NF-κB) signaling pathway, the phosphorylation, translocation, and DNA-binding activity of NF-κB were detected using western blot analysis, immunofluorescence analysis, electrophoretic mobility shift assay, and enzyme-linked immunosorbent assay analysis. High-frequency low-level diode laser irradiation decreased inflammatory cytokine expression in IL-1ß-treated chondrocytes. Moreover, high-frequency low-level diode laser irradiation decreased the phosphorylation, nuclear translocation, and DNA-binding activity of NF-κB in the IL-1ß-treated state. However, irradiation alone did not affect NF-κB activity. Thus, high-frequency low-level diode laser irradiation at 8 J/cm2 can reduce inflammatory cytokine expressions in normal human articular chondrocytes through NF-κB regulation. These findings indicate that high-frequency low-level diode laser irradiation may reduce the expression of inflammatory cytokines in OA and RA.
Subject(s)
Chondrocytes , NF-kappa B , Cells, Cultured , Chondrocytes/pathology , Cytokines/metabolism , Humans , Interleukin-1beta/metabolism , Interleukin-1beta/pharmacology , Lasers, Semiconductor/therapeutic use , NF-kappa B/metabolism , Signal TransductionABSTRACT
Brain state varies from moment to moment. While brain state can be defined by ongoing neuronal population activity, such as neuronal oscillations, this is tightly coupled with certain behavioural or vigilant states. In recent decades, abnormalities in brain state have been recognised as biomarkers of various brain diseases and disorders. Intriguingly, accumulating evidence also demonstrates mutual interactions between brain states and disease pathologies: while abnormalities in brain state arise during disease progression, manipulations of brain state can modify disease pathology, suggesting a therapeutic potential. In this review, by focusing on Alzheimer's disease (AD), the most common form of dementia, we provide an overview of how brain states change in AD patients and mouse models, and how controlling brain states can modify AD pathology. Specifically, we summarise the relationship between AD and changes in gamma and slow oscillations. As pathological changes in these oscillations correlate with AD pathology, manipulations of either gamma or slow oscillations can modify AD pathology in mouse models. We argue that neuromodulation approaches to target brain states are a promising non-pharmacological intervention for neurodegenerative diseases.
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Neural activity is diverse, and varies depending on brain regions and sleep/wakefulness states. However, whether astrocyte activity differs between sleep/wakefulness states, and whether there are differences in astrocyte activity among brain regions remain poorly understood. Therefore, in this study, we recorded astrocyte intracellular calcium (Ca2+) concentrations of mice during sleep/wakefulness states in the cortex, hippocampus, hypothalamus, cerebellum, and pons using fiber photometry. For this purpose, male transgenic mice expressing the genetically encoded ratiometric Ca2+ sensor YCnano50 specifically in their astrocytes were used. We demonstrated that Ca2+ levels in astrocytes substantially decrease during rapid eye movement (REM) sleep, and increase after the onset of wakefulness. In contrast, differences in Ca2+ levels during non-REM (NREM) sleep were observed among the different brain regions, and no significant decrease was observed in the hypothalamus and pons. Further analyses focusing on the transition between sleep/wakefulness states and correlation analysis with the duration of REM sleep showed that Ca2+ dynamics differs among brain regions, suggesting the existence of several clusters, i.e., the first comprising the cortex and hippocampus, the second comprising the hypothalamus and pons, and the third comprising the cerebellum. Our study thus demonstrated that astrocyte Ca2+ levels change substantially according to sleep/wakefulness states. These changes were consistent in general unlike neural activity. However, we also clarified that Ca2+ dynamics varies depending on the brain region, implying that astrocytes may play various physiological roles in sleep.SIGNIFICANCE STATEMENT Sleep is an instinctive behavior of many organisms. In the previous five decades, the mechanism of the neural circuits controlling sleep/wakefulness states and the neural activities associated with sleep/wakefulness states in various brain regions have been elucidated. However, whether astrocytes, which are a type of glial cell, change their activity during different sleep/wakefulness states was poorly understood. Here, we demonstrated that dynamic changes in astrocyte Ca2+ concentrations occur in the cortex, hippocampus, hypothalamus, cerebellum, and pons of mice during natural sleep. Further analyses demonstrated that Ca2+ dynamics slightly differ among different brain regions, implying that the physiological roles of astrocytes in sleep/wakefulness might vary depending on the brain region.
Subject(s)
Astrocytes/metabolism , Brain/metabolism , Calcium/metabolism , Sleep/physiology , Wakefulness/physiology , Animals , Male , Mice , Mice, TransgenicABSTRACT
The lateral habenula (LHb) is a brain structure which is known to be pathologically hyperactive in depression, whereby it shuts down the brains' reward systems. Interestingly, inhibition of the LHb has been shown to have an antidepressant effect, hence making the LHb a fascinating subject of study for developing novel antidepressant therapies. Despite this however, the exact mechanisms by which inhibitory signalling is processed within the LHb remain incompletely understood. Some studies have proposed the existence of locally targeting inhibitory interneuron populations within the LHb. One such population is believed to be akin to neocortical neurogliaform cells, yet specific molecular markers for studying these neurons are sparse and hence their function remains elusive. Recently, neuron-derived neurotrophic factor (NDNF) has been proposed as one such marker for neocortical neurogliaform cells. Using a combination of histological, physiological and optogenetic tools, we hence sought to first validate if NDNF was selectively expressed by such inhibitory neurons within the neocortex, and then if it was confined to a similar population within the LHb. While we report this to be true for the neocortex, we find no such evidence within the LHb; rather that NDNF is expressed without restriction to a particular neuronal subpopulation. These results hence indicate that molecular markers can represent broadly diverse populations of neurons on a region-to-region basis and that therefore each population as defined by molecular marker expression should be validated in each brain structure.