Language：Japanese   Publisher：Journal of Dental Research  

The relationship between oral health and the development of Alzheimer’s disease (AD) in the elderly is not yet well understood. In this regard, the association between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-β(1–42) (Aβ42) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Aβ42 oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Aβ42 oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and AppNL-G-F knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Aβ42 oligomer processing in the Vmes, which exhibits high amyloid-β (Aβ) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Aβ42 oligomer kinetics. Autophagosome-like membranes, which stained positive for Aβ, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Aβ in AppNL-G-F mice. By contrast, there was strong immunopositivity for extracellular Aβ42 oligomers with the formation of Aβ42 oligomer clusters in AppNL-G-F mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Aβ42 oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Aβ42 oligomers in AppNL-G-F mice. These results suggest that autophagy maintains homeostasis in Vmes neurons and that deterioration of autophagy due to aging or neurodegeneration leads to the diffusion of Aβ42 oligomers into the extracellular space and possibly the development of AD.

DOI： 10.1177/00220345231156095

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(株)ワールドプランニング  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

The rapid aging of the population makes the detection and prevention of frailty increasingly important. Oral frailty has been proposed as a novel frailty phenotype and is defined as a decrease in oral function coexisting with a decline in cognitive and physical functions. Oral frailty has received particular attention in relation to Alzheimer's disease (AD). However, the pathomechanisms of oral frailty related to AD remain unknown. It is assumed that the mesencephalic trigeminal nucleus (Vmes), which controls mastication, is affected by AD pathology, and as a result, masticatory function may be impaired. To investigate this possibility, we included male 3 × Tg-AD mice and their non-transgenic counterpart (NonTg) of 3–4 months of age in the present study. Immunohistochemistry revealed amyloid-β deposition and excessive tau phosphorylation in the Vmes of 3 × Tg-AD mice. Furthermore, vesicular glutamate transporter 1-immunopositive axon varicosities, which are derived from Vmes neurons, were significantly reduced in the trigeminal motor nucleus of 3 × Tg-AD mice. To investigate whether the AD pathology observed in the Vmes affects masticatory function, we analyzed electromyography of the masseter muscle during feeding. The 3 × Tg-AD mice showed a significant delay in masticatory rhythm compared to NonTg mice. Furthermore, we developed a system to simultaneously record bite force and electromyography of masseter, and devised a new method to estimate bite force during food chewing in mice. Since the muscle activity of the masseter showed a high correlation with bite force, it could be accurately estimated from the muscle activity. The estimated bite force of 3 × Tg-AD mice eating sunflower seeds was predominantly smaller than that of NonTg mice. However, there was no difference in masseter weight or muscle fiber cross-sectional area between the two groups, suggesting that the decreased bite force and delayed mastication rhythm observed in 3 × Tg-AD mice were not due to abnormality of the masseter. In conclusion, the decreased masticatory function observed in 3 × Tg-AD mice was most likely caused by AD pathology in the Vmes. Thus, novel quantitative analyses of masticatory function using the mouse model of AD enabled a comprehensive understanding of oral frailty pathogenesis.

DOI： 10.3389/fnagi.2022.935033

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society for Neuroscience  

DOI： 10.1523/eneuro.0567-20.2021

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Language：Japanese   Publisher：Alzheimer's & dementia : the journal of the Alzheimer's Association  

BACKGROUND: Periodontitis, a chronic systemic inflammatory disease, is a common health problem in the elderly. With increasing recognition that inflammation plays a key role in the pathophysiology of Alzheimer's disease (AD), our research team has been studying how systemic inflammation affects the brain immune responses. Aging is a major risk factor for both periodontitis and AD. As aging causes dysregulation of immune responses, we aimed to define the roles of cytokines in the pathogenesis of periodontitis and AD. METHODS: To induce experimental periodontitis, female WT mice were injected with heat-killed P. gingivalis into their buccal mucosa three times per week every other week for a total of 5 weeks. Another group of mice were injected with IL-1b and TNF-a following the same timeline as above. Sickness Behavior and cognitive functions were assessed through open field and puzzle box test. Mandibular jaws were harvested for Micro-CT scan. Different brain regions were harvested for biochemical analysis. RESULTS: Mice injected with heat-killed bacteria had worsened long-term memory functions. It also significantly increased periodontal bone loss, which was accompanied by increased gene expression levels of IL-1b and TNF-a in the gums. Significant elevated levels of pro-inflammatory cytokines in the liver as well as different brain regions were also observed. Immunostaining revealed increased levels of phospho-tau in WT mice injected with heat-killed bacteria, suggesting that elevated systemic cytokine levels caused by the injection of heat-killed bacteria can lead to the appearance of AD pathology. Another group of mice injected with IL-1b and TNF-a displayed hyperactivity and worsened short-term memory functions. Injections of cytokines also induced periodontal bone loss, which was accompanied by elevated levels of inflammatory cytokines in the liver as well as different brain regions. CONCLUSION: Taken together, our study revealed that increased cytokine immune response in the gums led to periodontal bone loss, brain inflammation and modulated the cognitive functions of WT mice. This research demonstrated that cytokines play a crucial role in the pathogenesis of both periodontitis and AD. Acknowledgement: The study is supported by Health and Medical Research Fund (HMRF 04151216) to RCCC. RPHW is awarded by Hong Kong PhD Fellowship.

DOI： 10.1002/alz.058464

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peripheral nerve injury, unlike those in the brain and spinal cord. We analyzed the origin and morphological features of sensory ganglionic macrophages after nerve ligation or transection using wild-type mice and mice with bone-marrow cell transplants. METHODS: After protecting the head of C57BL/6J mice with lead caps, they were irradiated and transplanted with bone-marrow-derived cells from GFP transgenic mice. The infraorbital nerve of a branch of the trigeminal nerve of wild-type mice was ligated or the infraorbital nerve of GFP-positive bone-marrow-cell-transplanted mice was transected. After immunostaining the trigeminal ganglion, the structures of the ganglionic macrophages, neurons, and satellite glial cells were analyzed using two-dimensional or three-dimensional images. RESULTS: The number of damaged neurons in the trigeminal ganglion increased from day 1 after infraorbital nerve ligation. Ganglionic macrophages proliferated from days 3 to 5. Furthermore, the numbers of macrophages increased from days 3 to 15. Bone-marrow-derived macrophages increased on day 7 after the infraorbital nerve was transected in the trigeminal ganglion of GFP-positive bone-marrow-cell-transplanted mice but most of the ganglionic macrophages were composed of tissue-resident cells. On day 7 after infraorbital nerve ligation, ganglionic macrophages increased in volume, extended their processes between the neurons and satellite glial cells, and contacted these neurons. Most of the ganglionic macrophages showed an M2 phenotype when contact was observed, and little neuronal cell death occurred. CONCLUSION: Most of the macrophages that appear after a nerve injury are tissue-resident, and these make direct contact with damaged neurons that act in a tissue-protective manner in the M2 phenotype. These results imply that tissue-resident macrophages signal to neurons directly through physical contact.

DOI： 10.1186/s12974-021-02283-z

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

Background: Epidemiological studies have shown that tooth loss is associated with Alzheimer's disease (AD) and dementia. However, the molecular and cellular mechanisms by which tooth loss causes AD remain unclear.Objective: We investigated the effects of tooth loss on memory impairment and AD pathogenesis in App(NL-G-F) mice.Methods: Maxillary molar teeth on both sides were extracted from 2-month-old App(NL-G-F) mice, and the mice were reared for 2 months. The short- and long-term memory functions were evaluated using a novel object recognition test and a passive avoidance test. Amyloid plaques, amyloid-beta (A beta) levels, glial activity, and neuronal activity were evaluated by immunohistochemistry, A beta ELISA, immunofluorescence staining, and western blotting. The mRNA expression levels of neuroinflammatory cytokines were determined by qRT-PCR analysis.Results: Tooth loss induced memory impairment via an amyloid-cascade-independent pathway, and decreased the neuronal activity, presynaptic and postsynaptic protein levels in both the cortex and hippocampus. Interestingly, we found that tooth loss induced glial activation, which in turn leads to the upregulation of the mRNA expression levels of the neuroinflammation cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta in the hippocampus. We also found that tooth loss activated a stress-activated protein kinase, c-Jun N-terminal kinase (JNK), and increased heat shock protein 90 (HSP90) levels in the hippocampus, which may lead to a glial activation.Conclusion: Our findings suggest that taking care of teeth is very important to preserve a healthy oral environment, which may reduce the risk of cognitive dysfunction.

DOI： 10.3233/JAD-201055

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Publisher：日本組織細胞化学会  

<p>Proprioception from masticatory apparatus and periodontal ligaments comes through the trigeminal mesencephalic nucleus (Vmes). We evaluated the effects of tooth loss on neurodegeneration of the Vmes and trigeminal motor nucleus (Vmo). Bilateral maxillary molars of 2-month-old C57BL/6J mice were extracted under anesthesia. Neural projections of the Vmes to the periodontium were confirmed by injecting Fluoro-Gold (FG) retrogradely into the extraction sockets, and for the anterograde labeling adeno-associated virus encoding green fluorescent protein (AAV-GFP) was applied. For immunohistochemistry, Piezo2, ATF3, Caspase 3, ChAT and TDP-43 antibodies were used. At 1 month after tooth extraction, the number of Piezo2-immunoreactive (IR) Vmes neurons were decreased significantly. ATF3-IR neurons were detected on day 5 after tooth extraction. Dead cleaved caspase-3-IR neurons were found among Vmes neurons on days 7 and 12. In the Vmo, neuronal cytoplasmic inclusions (NCIs) formation type of TDP-43 increased at 1 and 2 months after extraction. These indicate the existence of neural projections from the Vmes to the periodontium in mice and that tooth loss induces the death of Vmes neurons followed by TDP-43 pathology in the Vmo. Therefore, tooth loss induces Vmes neuronal cell death, causing Vmo neuro­degeneration and presumably affecting masticatory function.</p>

DOI： 10.1267/ahc.20-00036

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs. Objective: We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-ß (Aß) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function. Methods: The molars of 3×Tg-AD mice were extracted, and the mice were reared for one week to 4 months. Immunohistochemical analysis, and spatial learning/memory assessment using the Barnes maze were carried out. Results: In 4-month-old 3×Tg-AD mice, aggregated cytotoxic Aß42 was found in granules in Vmes neurons. Neuronal death in the Vmes occurred after tooth extraction, resulting in the release of cytotoxic Aß42 and an increase in CD86 immunoreactive microglia. Released Aß42 damaged the LC, in turn inducing a significant reduction in hippocampal neurons in the CA1 and CA3 regions receiving projections from the LC. Based on spatial learning/memory assessment, after the tooth extraction in the 4-month-old 3×Tg-AD mice, increased latency was observed in 5-month-old 3×Tg-AD mice 1 month after tooth extraction, which is similar increase of latency observed in control 8-month-old 3×Tg-AD mice. Measures of cognitive deficits suggested an earlier shift to dementia-like behavior after tooth extraction. Conclusion: These findings suggest that tooth extraction in the predementia stage can trigger the spread of neurodegeneration from the Vmes, LC, and hippocampus and accelerate the onset of dementia.

DOI： 10.3233/JAD-200257

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Purpose of Review: Alzheimer’s disease (AD) is a major subtype of dementia. Recent cohort studies have demonstrated that loss of masticatory function, periodontitis, and/or tooth loss are risk factors for AD. The present review provides an overview of the existing literature as well as recent evidence regarding the relationship between tooth loss and the onset of AD. Recent Findings: In the dental field, tooth loss is one of the most relevant factors related to the prevalence of AD. This is important in a progressively elderly population because tooth loss is associated with the risk of mild cognitive impairment (MCI) developing into dementia due to a cascade of neurodegeneration caused by damage to periodontal tissues via the trigeminal nerve, locus coeruleus (LC), and hippocampus. Additionally, periodontal disease and/or the loss of masticatory function are likely to exacerbate factors associated with AD. Summary: Tooth loss in the elderly may cause neurodegeneration and act as a trigger for the progression from MCI to dementia. Moreover, neurodegeneration due to tooth loss is thought to exacerbate the accumulation of AD-specific amyloid-β and phosphorylated tau proteins, which worsen the pathological condition of AD. Although further evidence is needed, novel strategies for avoiding the progression to AD due to tooth loss in the elderly are required.

DOI： 10.1007/s40496-019-0219-1

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Publisher：Springer Tokyo  

The anatomical variations of the confluence of sinuses were examined, focusing on the continuity of the superior sagittal sinus (SSS) and the transverse sinuses (TSs). In the 142 specimens studied, there were 72 symmetric cases (50.7%) and 70 asymmetric cases (49.3%). The symmetric group (no dominant type) was categorized into 34 cases of bifurcation (23.9%) and 38 cases of confluence (26.8%). The asymmetric group was categorized into 54 cases of the right-dominant type (38.0%) and 16 cases of the left-dominant type (11.3%). The right-dominant type was further categorized into 38 partially-communicating (26.8%) and 16 non-communicating types (11.3%). The left-dominant type was categorized into 11 partially-communicating (7.7%) and 5 non-communicating types (3.5%). In summary, the SSS asymmetrically drained into one TS in about half of the cases studied. The right-dominant type was about three to four times as common as the left-dominant type. The draining pattern shown by the asymmetric group could provoke intracranial hypertension due to unilateral jugular vein obstruction. In order to avoid this risk in cases of neck dissection, jugular vein catheterization, or hypercoagulopathy, preoperative evaluations of the dural sinus variations via MR venography, three-dimensional CT, or plain X-ray of the skull are recommended.

DOI： 10.1007/s12565-018-0436-z

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Publisher：Anatomical Science International  

DOI： 10.1007/s12565-018-0436-z

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Publisher：(一社)歯科基礎医学会  

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DOI： 10.1007/s12565-018-0436-z

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Publisher：Springer Tokyo  

The clinical anatomy of the recurrent artery of Heubner (RAH) was examined, focusing on its number, origin, and course, in a large number of brain specimens. We studied 724 RAH in total from 357 brain specimens (714 hemispheres). In 98.74 % of 714 cases there were one or more RAHs, while it was absent in 1.26 % of cases. There was a single RAH in 96.22 % of cases, double in 2.38 % of cases, and triple in 0.14 % of cases. In this study, three origin types of the RAH were defined. We defined A1 and A2 segment of the anterior cerebral artery (ACA) as the artery from the origin of the ACA to the junction of the anterior communicating artery (AComA) and the artery from the junction of the AComA to the anterior border of the corpus callosum, respectively. In 76.2 % of 724 arteries, the RAH originated from the junction of the A1 and A2 segment of the ACA. In 16.3 %, the RAH originated from the A2 segment of the ACA. In 7.5 %, the RAH originated from the A1 segment of the ACA. The course of the RAH was superior to the A1 segment of the ACA in 30.1 % of 724 arteries, anterior in 62.2 %, and posterior in 7.7 %. It is of great importance for neurosurgeons to understand the detailed anatomical variations of the RAH before operating to prevent operative complications resulting in neurological deficits.

DOI： 10.1007/s12565-017-0415-9

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Publisher：シュプリンガー・ジャパン(株)  

脳標本357個(半脳714個)に対し、Heubner反回動脈(RAH)(計724)の臨床解剖学的検討を行い、なかでも、RAHの数、起始、走行の変異について調査した。その結果、RAHの数は、半脳の1.26%で0個、96.22%で1個、2.38%で2個、0.14%で3個で、RAH起始部の外径は、0.69±0.25mmで、外径範囲は0.32〜1.11mmであった。なお、RAHの76.2%は前大脳動脈のA1区とA2区間から始まり、16.3%はA2区から、7.5%はA1区から起始し、RAHの走行では、前大脳動脈のA1区に対して30.1%が上方、62.2%が前方、7.7%が後方であった。なお、異常例は3例認められ、1例目はRAHが副中大脳動脈から分枝し、起始部から遠位で2本のRAHに分かれていた。2例目はRAHが眼窩前頭動脈と共通の幹から起始しており、3例目はRAHが眼窩前頭動脈および前頭極動脈と共通の幹から起始していた。

Publisher：SPRINGER  

The anatomical variations of the confluence of sinuses were examined, focusing on the continuity of the superior sagittal sinus (SSS) and the transverse sinuses (TSs). In the 142 specimens studied, there were 72 symmetric cases (50.7%) and 70 asymmetric cases (49.3%). The symmetric group (no dominant type) was categorized into 34 cases of bifurcation (23.9%) and 38 cases of confluence (26.8%). The asymmetric group was categorized into 54 cases of the right-dominant type (38.0%) and 16 cases of the left-dominant type (11.3%). The right-dominant type was further categorized into 38 partially-communicating (26.8%) and 16 non-communicating types (11.3%). The left-dominant type was categorized into 11 partially-communicating (7.7%) and 5 non-communicating types (3.5%). In summary, the SSS asymmetrically drained into one TS in about half of the cases studied. The right-dominant type was about three to four times as common as the left-dominant type. The draining pattern shown by the asymmetric group could provoke intracranial hypertension due to unilateral jugular vein obstruction. In order to avoid this risk in cases of neck dissection, jugular vein catheterization, or hypercoagulopathy,

DOI： 10.1007/s12565-018-0436-z

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Publisher：Bio Integration Society  

Ti implants have been used primarily for current dental implants．However the peri-implant inflammation is a seriousploblem．In order to improve the adhesion between the abutment and the epithelium，Si-containing calciumphosphate thin film containing Si-Ca-P was coated on Ti using sputtering method from a mixture of hydroxyapatiteand SiO2 as a target．Then，cell adhesion on the thin film was evaluated．Mouse embryo derived fibroblasts(NIH-3T3) were seeded on Si-containing calcium phosphate thin films．After 48 hours of cell seeding, fluorescenceimage of cells and the number of attached cells were observed using a microscope．As a result，the number of attached cells on the Si- containing calcium phosphate thin films increased withincreasing Si content，and reached a maximum of 46 (cells/frame) on the film with 30% of SiO2 /SiO2 +HAtarget．Then the number of attached cells decreased to 24 (cells/frame) with the film with 100% of SiO2 target．

DOI： 10.32176/biointeg.8.1_123

Publisher：WILEY  

The rodent orbitofrontal cortex is involved in a variety of cognitive and behavioral functions that require thalamic input to be successfully expressed. Although the thalamic nucleus submedius (Sm) is a major source of afferents to the orbitofrontal cortex, thalamocortical projection from the Sm has not been fully elucidated. In the present study, we first divided the rat Sm into dorsal and ventral parts according to the distribution of vesicular glutamate transporter 2-immunoreactive varicosities, which were somatosensory afferents from the brain stem. Subsequently we investigated dendritic and axonal arborizations of individual dorsal and ventral Sm neurons by visualizing the processes with Sindbis virus vectors expressing membrane-targeted fluorescent proteins. The number of dendritic processes of ventral Sm neurons was greater than that of dorsal Sm neurons. In the cerebral cortex, all the reconstructed Sm neurons sent axons primarily to layers 2–5. Interestingly, dorsal Sm neurons formed a single axon arbor exclusively within the ventrolateral orbital area, whereas ventral Sm neurons made two axon arbors in the lateral orbital and ventral orbital areas simultaneously. The spread of each axon arbor was 500–1000 µm in diameter in the direction tangential to the cortical surface. These results indicate that the dorsal and ventral Sm comprise two distinct thalamocortical pathways. The dorsal Sm pathway relay somatosensory information to the ventrolateral orbital area and may be involved in emotional and aversive aspects of nociceptive information processing, whereas the ventral Sm pathway seems to co-activate distant orbitofrontal cortical areas, and may link their functions under certain circumstances.

DOI： 10.1002/cne.24306

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Publisher：バイオインテグレーション学会  

スパッタリング法によるTi中間層及びハイドロキシアパタイト(HA)薄膜の作製を試みた。審美性評価の観点から、透過性を確認するため、石英基板への成膜試料も作製した。成膜したHA薄膜は、120℃で24時間水熱処理を行い、結晶化させた。成膜後、膜の表面観察により、膜の剥離状態及び透明性を評価した。骨親和性の評価には、ラット頭頂骨由来初代培養系骨芽細胞を用い、骨形成実験を行った。Tiを中間層とすることで、polyetheretherketone(PEEK)基板上へのHA成膜が可能であることが示唆された。水熱処理の有無に関わらず、Ti中間層50nm以上では金属光沢があり、透明性は認めなかったが、Ti中間層10nm以下では、うっすらと灰色を認め、透明性は確保された。特に、Ti中間層5nmでは、石英板単体と比較しても高い透明性が確保されていた。骨形成面積は、Ti 100nm-HAとTi板HAが最も高くTi 100nm-HAについては、HA膜がPEEK板に付与されることで、従来のTi板HAに匹敵する骨親和性を示した。HAが付与されたTi 5nm-HAは、Ti 100nm-HAと比べて、有意に低値となった。

Publisher：Elsevier Ltd  

Peripheral nociceptive stimuli from orofacial structures are largely transmitted by the trigeminal nerve. According to the peripheral noxious stimuli, neurons in the trigeminal ganglion (TG) produce neuropeptides such as substance P, and calcitonin-gene-related peptide, etc. Beside the production of neuropeptides, there exists unique non-synaptic interaction system between maxillary and mandibular neurons in the TG. Neurons in the TG are surrounded by satellite glial cells (SGCs), which initially receive the signal from TG neurons. These activated SGCs secrete a transmitter to activate adjacent SGCs or TG neurons, thereby amplifying the signal, for example, from mandibular neurons to maxillary neurons in the TG. Similar to the dorsal root ganglion, in the TG, microglia/macrophage-like cells (MLCs) are activated by uptake of a transmitter from TG neurons or SGCs. This communication between neurons, SGCs, and MLCs results in responses such as ectopic pain, hyperesthesia, or allodynia. The focus of this review is the cooperative interaction of the maxillary and mandibular nerves in the TG by neuropeptides, and adenosine 3′-phosphate (ATP) signaling from neurons to SGCs and MLCs. Stimulated neurons either secrete ATP by means of vesicular nucleotide transporters, or secrete neuropeptides from the neuronal cell body to mediate signal transmission.

DOI： 10.1016/j.jdsr.2017.01.003

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DOI： 10.1002/cne.12646

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Publisher：WILEY-BLACKWELL  

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166–185, 2017. © 2016 Wiley Periodicals, Inc.

DOI： 10.1002/cne.24054

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Publisher：Bio Integration Society  

Polyetheretherketone (PEEK) is a semi-crystalline polymer with outstanding mechanical properties, bone-likestiffness and suitable biocompatibility that has attracted much interest as a biomaterial for dental implants.However, the bio-inert surface of the PEEK limits its medical applications when direct osteintegration betweenthe implants and the host tissue. In this work, we fabricated hydroxyapatite (HA) thin films on a PEEK substratewith a titanium (Ti) intermediate layer using a sputtering to improve adhesion strength of the HA filmto the PEEK. The HA film was not coated without the Ti intermediate layer, whereas the HA films with the Tiintermediate layer was successfully fabricated on the PEEK regardless of the thickness of the Ti intermediatelayers. The HA films with 5 and 10 nm Ti intermediated layer have transparency. In the cell culture, the boneformation area on the HA film with 100 nm Ti intermediated layer was larger than that on the HA film with 5nm Ti intermediated layer.

DOI： 10.32176/biointeg.7.1_81

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DOI： 10.1007/BF00271276

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Publisher：日本歯科医学会  

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Publisher：(一社)歯科基礎医学会  

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Publisher：(一社)歯科基礎医学会  

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Publisher：全国保険医団体連合会  

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