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1.
Brain Nerve ; 73(11): 1193-1199, 2021 Nov.
Article in Japanese | MEDLINE | ID: mdl-34759055

ABSTRACT

In mammals, the intrinsic circadian clock regulates various physiological rhythms, including sleep-wake cycles. These circadian rhythms can be entrained to daily 24-hour light-dark cycles by virtue of photoreception within the retina. The photo-entrainment of circadian rhythms is predominantly mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). In this article, we review the mechanisms of action of ipRGC photoreception, the retinal circuit involving ipRGCs, and the heterogeneity of ipRGCs in mice.


Subject(s)
Circadian Rhythm , Retinal Ganglion Cells , Animals , Mice
2.
Sci Adv ; 7(41): eabi9784, 2021 Oct 08.
Article in English | MEDLINE | ID: mdl-34613771

ABSTRACT

Most vertebrate lineages retain a tetrachromatic visual system, which is supported by a functional combination of spectrally distinct multiple cone photoreceptors, ultraviolet (UV), blue, green, and red cones. The blue cone identity is ensured by selective expression of blue (sws2) opsin, and the mechanism is poorly understood because sws2 gene has been lost in mammalian species such as mouse, whose visual system has been extensively studied. Here, we pursued loss-of-function studies on transcription factors expressed predominantly in zebrafish cone photoreceptors and identified Foxq2 as a blue cone­specific factor driving sws2 gene expression. Foxq2 has dual functions acting as an activator of sws2 transcription and as a suppressor of UV (sws1) opsin transcription in blue cones. A wide range of vertebrate species retain both foxq2 and sws2 genes. We propose that Foxq2-dependent sws2 expression is a prevalent regulatory mechanism that was acquired at the early stage of vertebrate evolution.

3.
Int J Hyperthermia ; 38(1): 1077-1085, 2021.
Article in English | MEDLINE | ID: mdl-34278925

ABSTRACT

OBJECTIVES: To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). SETTING: Observational study with crossover design. METHODS: Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. RESULTS: BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). CONCLUSION: While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.


Subject(s)
Brain-Derived Neurotrophic Factor , Water , Hot Temperature , Humans , Immersion , Male , Temperature
4.
J Phys Ther Sci ; 32(7): 444-448, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32753784

ABSTRACT

[Purpose] Previous studies have demonstrated a link between core body temperature and interleukin-6 production. Recent studies have reported that 20 minutes of head-out immersion in hot water (42°C) increased serum interleukin-6 levels in young males. This study aimed to compare the efficacy of head-out immersion in hot water (42°C) on serum interleukin-6 levels in seven elderly (66-75 years old) and eight young males (21-32 years old). [Participants and Methods] Venous blood samples were drawn at rest, immediately after head-out immersion in hot water (42°C), after 1 hour, and after 2 hours. Levels of serum interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein; blood cell counts; and core temperature were measured. [Results] It was found that 20 minutes of head-out immersion in hot water (42°C) increased the core temperature in both the elderly and young participants; however, the rise in core temperature was more attenuated in elderly participants. Serum interleukin-6 levels were significantly higher in young participants 1 hour after the head-out immersion in hot water (42°C); however, serum interleukin-6 levels did not change in elderly participants. Serum tumor necrosis factor-α and high-sensitivity C-reactive protein levels remained constant throughout the study the elderly and young participants. [Conclusion] The current study demonstrated that head-out immersion in hot water (42°C) more attenuated core temperature and interleukin-6 levels in elderly participants than in young participants. We assert that these differences are likely to be related to age-related changes in core temperature regulation and muscle fibers.

5.
Commun Biol ; 2: 364, 2019.
Article in English | MEDLINE | ID: mdl-31602413

ABSTRACT

The pineal gland functioning as a photoreceptive organ in non-mammalian species is a serial homolog of the retina. Here we found that Brain-specific homeobox (Bsx) is a key regulator conferring individuality on the pineal gland between the two serially homologous photoreceptive organs in zebrafish. Bsx knock-down impaired the pineal development with reduced expression of exorh, the pineal-specific gene responsible for the photoreception, whereas it induced ectopic expression of rho, a retina-specific gene, in the pineal gland. Bsx remarkably transactivated the exorh promoter in combination with Otx5, but not with Crx, through its binding to distinct subtypes of PIRE, a DNA cis-element driving Crx/Otx-dependent pineal-specific gene expression. These results demonstrate that the identity of pineal photoreceptive neurons is determined by the combinatorial code of Bsx and Otx5, the former confers the pineal specificity at the tissue level and the latter determines the photoreceptor specificity at the cellular level.


Subject(s)
Homeodomain Proteins/metabolism , Pineal Gland/metabolism , Zebrafish Proteins/metabolism , Animals , Animals, Genetically Modified , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Otx Transcription Factors/metabolism , PAX6 Transcription Factor/metabolism , Pineal Gland/cytology , Pineal Gland/growth & development , Promoter Regions, Genetic , Rhodopsin/metabolism , Trans-Activators/metabolism , Transcription Factors/metabolism , Zebrafish , Zebrafish Proteins/genetics
6.
Proc Natl Acad Sci U S A ; 116(10): 4651-4660, 2019 03 05.
Article in English | MEDLINE | ID: mdl-30765521

ABSTRACT

Color discrimination in the vertebrate retina is mediated by a combination of spectrally distinct cone photoreceptors, each expressing one of multiple cone opsins. The opsin genes diverged early in vertebrate evolution into four classes maximally sensitive to varying wavelengths of light: UV (SWS1), blue (SWS2), green (RH2), and red (LWS) opsins. Although the tetrachromatic cone system is retained in most nonmammalian vertebrate lineages, the transcriptional mechanism underlying gene expression of the cone opsins remains elusive, particularly for SWS2 and RH2 opsins, both of which have been lost in the mammalian lineage. In zebrafish, which have all four cone subtypes, rh2 opsin gene expression depends on a homeobox transcription factor, sine oculis homeobox 7 (Six7). However, the six7 gene is found only in the ray-finned fish lineage, suggesting the existence of another evolutionarily conserved transcriptional factor(s) controlling rh2 opsin expression in vertebrates. Here, we found that the reduced rh2 expression caused by six7 deficiency was rescued by forced expression of six6b, which is a six7-related transcription factor conserved widely among vertebrates. The compensatory role of six6b was reinforced by ChIP-sequencing analysis, which revealed a similar pattern of Six6b- and Six7-binding sites within and near the cone opsin genes. TAL effector nuclease-induced genetic ablation of six6b and six7 revealed that they coordinately regulate SWS2 opsin gene expression. Mutant larvae deficient for these transcription factors showed severely impaired visually driven foraging behavior. These results demonstrate that in zebrafish, six6b and six7 govern expression of the SWS2 and RH2 opsins responsible for middle-wavelength sensitivity, which would be physiologically important for daylight vision.


Subject(s)
Homeodomain Proteins/metabolism , Opsins/metabolism , Rod Opsins/metabolism , Zebrafish Proteins/metabolism , Zebrafish/metabolism , Animals , Color , Color Vision , Gene Expression Regulation , Homeodomain Proteins/genetics , Opsins/genetics , Rod Opsins/genetics , Zebrafish/genetics , Zebrafish Proteins/genetics
7.
Int J Hyperthermia ; 34(6): 834-839, 2018 09.
Article in English | MEDLINE | ID: mdl-29157042

ABSTRACT

PURPOSE: Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations. METHODS: Eight healthy men performed 20 min head-out water immersion at 42 °C (hot-HOI) and 35 °C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7 days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30 min after the end of the HOI. Serum BDNF and S100ß, plasma cortisol, platelet and monocyte counts, and core body temperature (Tcb) were measured. RESULTS: Tcb was higher at the end of the hot-HOI and 15 min after hot-HOI (p < 0.01), but recovered to pre-HOI level at 30 min after hot-HOI. No change in Tcb was recorded during neutral-HOI. BDNF level was higher (p < 0.05) at the end of the hot-HOI and at 15 min after the end of hot-HOI, and returned to the baseline at 30 min after hot-HOI. S100ß, platelet count and monocyte count remained stable throughout the study. Cortisol level was lower at the end of the hot-HOI and returned to pre-HOI level during the recovery period. BDNF and S100ß, cortisol, and platelet and monocyte counts did not change throughout the neutral-HOI study. CONCLUSIONS: The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood-brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Immersion/physiopathology , Water/chemistry , Adult , Hot Temperature , Humans , Male
8.
PLoS One ; 12(10): e0187099, 2017.
Article in English | MEDLINE | ID: mdl-29073250

ABSTRACT

OBJECTIVE: Clinical evidence suggests that early mobilization of patients with acute stroke improves activity of daily living (ADL). The purpose of this study was to compare the utility of the physiatrist and registered therapist operating acute rehabilitation (PROr) applied early or late after acute stroke. SUBJECTS AND METHODS: This study was prospective cohort study, assessment design. Patients with acute stroke (n = 227) admitted between June 2014 and April 2015 were divided into three groups based on the time of start of PROr: within 24 hours (VEM, n = 47), 24-48 hours (EM, n = 77), and more than 48 hours (OM, n = 103) from stroke onset. All groups were assessed for the number of deaths during hospitalization, and changes in the Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), and Functional Independence Measure (FIM) at hospital discharge. INTERVENTIONS: All patients were assessed by physiatrists, who evaluated the specific needs for rehabilitation, and then referred them to registered physical therapists and occupational therapists to provide early mobilization (longer than one hour per day per patient). RESULTS: The number of deaths encountered during the PROr period was 13 (out of 227, 5.7%), including 2 (4.3%) in the VEM group. GCS improved significantly during the hospital stay in all three groups, but the improvement on discharge was significantly better in the VEM group compared with the EM and OM groups. FIM improved significantly in the three groups, and the gains in total FIM and motor subscale were significantly greater in the VEM than the other groups. CONCLUSIONS: PROr seems safe and beneficial rehabilitation to improve ADL in patients with acute stroke.


Subject(s)
Physiatrists , Physical Therapists , Stroke Rehabilitation , Aged , Female , Humans , Male , Prospective Studies
9.
J Mech Behav Biomed Mater ; 64: 113-24, 2016 12.
Article in English | MEDLINE | ID: mdl-27498422

ABSTRACT

This study aims at developing the prediction model of cyclic delamination lives of plasma-sprayed HAp coating on Ti-6Al-4V substrate by considering wear by interface contacts and dissolution effect by Simulated Body Fluid (SBF). Delamination of HAp coating can lead to loosening of implants stem and final failure in vivo. In the fracture mechanism of interfaces between HAp coating with Ti substrates, only adhesive strength (interracial tensile strength) or fatigue behavior by longitudinal cracking have been observed. Cyclic delamination mechanism by considering various loading modes and corrosion effect has not been revealed yet. The interface delamination rates by cyclic loading were much higher than those by static loading tests. The result clearly demonstrated that the interface demalination behaviors are dominated not by maximum stress, but by stress range. Surface profile measurement and SEM observation also demonstrated damages by interface contact or third body wear at delamination tips of HAp coating only in the cases of compressions. The mechanisms of acceleration on the delaminations are third-body wear or wedge effect by worn particles which increased mean stress level during cyclic loading. Cyclic loading tests under SBF also revealed that cyclic delamination lives were shortened probably due to crevice corrosion at interfaces. Dissolutions at the tips of delaminations were observed by SEM images under tensile loading condition in SBF. Linearly adding the effects of wear and dissolutions into Paris law could successfully predict the delamination lives of HAp coating for various loading ratios in SBF.


Subject(s)
Durapatite/chemistry , Prostheses and Implants , Titanium/chemistry , Alloys , Body Fluids , Solubility , Surface Properties
10.
Photochem Photobiol Sci ; 14(11): 1991-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26411960

ABSTRACT

In the chicken pineal gland, light stimuli trigger signaling pathways mediated by two different subtypes, Gt and G11. These G proteins may be activated by any of the three major pineal opsins, pinopsin, OPN4-1 and OPN4-2, but biochemical evidence for the coupling has been missing except for functional coupling between pinopsin and Gt. Here we investigated the relative expression levels and the functional difference among the three pineal opsins. In the chicken pineal gland, the pinopsin mRNA level was significantly more abundant than the others, of which the OPN4-2 mRNA level was higher than that of OPN4-1. In G protein activation assays, Gt was strongly activated by pinopsin in a light-dependent manner, being consistent with previous studies, and weakly activated by OPN4-2. Unexpectedly, illuminated OPN4-2 more efficiently activated G protein(s) that was endogenously expressed in HEK293T cells in culture. On the other hand, Gq, the closest analogue of G11, was activated only by OPN4-1 although the activity was relatively weak under these conditions. These results suggest that OPN4-1 and OPN4-2 couple with Gq and Gt, respectively. Two melanopsins, OPN4-1 and OPN4-2, appear to have acquired mutually different functions through the evolution.


Subject(s)
GTP-Binding Proteins/metabolism , Light , Rod Opsins/metabolism , Animals , Chickens , Enzyme Activation/radiation effects , Pineal Gland/chemistry , Pineal Gland/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rod Opsins/genetics
11.
Proc Biol Sci ; 282(1812): 20150659, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26180064

ABSTRACT

Colour discrimination in vertebrates requires cone photoreceptor cells in the retina, and high-acuity colour vision is endowed by a set of four cone subtypes expressing UV-, blue-, green- and red-sensitive opsins. Previous studies identified transcription factors governing cone photoreceptor development in mice, although loss of blue and green opsin genes in the evolution of mammals make it difficult to understand how high-acuity colour vision was organized during evolution and development. Zebrafish (Danio rerio) represents a valuable vertebrate model for studying colour vision as it retains all the four ancestral vertebrate cone subtypes. Here, by RT-qPCR and in situ hybridization analysis, we found that sine oculis homeobox homolog 7 (six7), a transcription factor widely conserved in ray-finned fish, is expressed predominantly in the cone photoreceptors in zebrafish at both the larval and the adult stages. TAL effector nuclease-based six7 knock-out revealed its roles in expression of green, red and blue cone opsin genes. Most prominently, the six7 deficiency caused a loss of expression of all the green opsins at both the larval and adult stages. six7 is indispensable for the development and/or maintenance of the green cones.


Subject(s)
Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Retinal Cone Photoreceptor Cells/metabolism , Rod Opsins/genetics , Zebrafish Proteins/genetics , Zebrafish/genetics , Animals , Homeodomain Proteins/metabolism , In Situ Hybridization , Real-Time Polymerase Chain Reaction , Rod Opsins/metabolism , Zebrafish/growth & development , Zebrafish/metabolism , Zebrafish Proteins/metabolism
12.
J Vet Med Sci ; 76(1): 133-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24025433

ABSTRACT

Feline pituitary tumors are rare. An 8-year-old male Japanese domestic cat presented with anorexia and emaciation. The cat died 17 days after admission from progressive neurological symptoms. At necropsy, a pituitary tumor measuring 25 × 18 × 15 mm was found. Microscopically, the tumor was divided into multiple lobules and had grown invasively into the adjacent brain tissue and sphenoid bone. Tumor cells had pleomorphic nuclei with prominent centrally located nucleoli and abundant amphophilic polygonal cytoplasm. Immunohistochemically, the tumor cells stained with anti-adrenocorticotropic hormone (ACTH), α-melanin-stimulating hormone (MSH) and ß-endorphin antibodies. Ultrastructurally, the cytoplasm of the tumor cells contained various sized secretory granules. Based on these pathological findings, this tumor was diagnosed as pituitary carcinoma originated from pars intermedia cells.


Subject(s)
Cat Diseases/pathology , Cushing Syndrome/veterinary , Pituitary Neoplasms/veterinary , Animals , Cats , Cushing Syndrome/pathology , Fatal Outcome , Immunohistochemistry/veterinary , Male , Microscopy, Electron/veterinary , Pituitary Neoplasms/pathology , Pituitary Neoplasms/ultrastructure
13.
J Neurosci ; 33(9): 3834-43, 2013 Feb 27.
Article in English | MEDLINE | ID: mdl-23447595

ABSTRACT

Nonvisual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of nonvisual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light but does not require the eyes, pineal gland, or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical nonvisual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain.


Subject(s)
Movement/physiology , Opsins/metabolism , Photoreceptor Cells, Vertebrate/physiology , Rhombencephalon/cytology , Stereotyped Behavior/physiology , Age Factors , Analysis of Variance , Animals , Biomechanical Phenomena , Biophysics , Calcium/metabolism , Embryo, Nonmammalian , Female , Male , Microscopy, Confocal , Morpholinos/pharmacology , Movement/drug effects , Movement/radiation effects , Muscle Cells/drug effects , Muscle Cells/radiation effects , Neural Pathways/drug effects , Neural Pathways/physiology , Neural Pathways/radiation effects , Opsins/chemistry , Photic Stimulation , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/radiation effects , Rhombencephalon/physiology , Stereotyped Behavior/drug effects , Stereotyped Behavior/radiation effects , Time Factors , Zebrafish
14.
J Vet Med Sci ; 75(5): 639-41, 2013.
Article in English | MEDLINE | ID: mdl-23229541

ABSTRACT

A 13-year-old castrated male Labrador retriever dog presented with a mass caudal to the first molar of his left mandible. Although the tumor was excised, a recurrent tumor was detected one month later and resected. Both tumors displayed invasive growth and were composed of neoplastic proliferation arranged in irregular lobules, nests and cords continuous with mucosal epithelium. The most prominent feature of the tumors was the presence of many proliferating spindle cells admixed with palisading basal-like cells, acanthocytes and stellate cells. In immunohistochemical examinations, the spindle cells were found to be positive for vimentin; cytokeratin AE1/AE3, 5/6, 14 and 19; and p63. The other neoplastic cells were positive for all of these markers shown above except vimentin. Based on these findings, the tumors were diagnosed as spindle cell ameloblastic carcinoma.


Subject(s)
Ameloblastoma/veterinary , Carcinoma/veterinary , Dog Diseases/metabolism , Dog Diseases/pathology , Jaw Neoplasms/veterinary , Neoplasm Recurrence, Local/veterinary , Ameloblastoma/metabolism , Ameloblastoma/pathology , Animals , Carcinoma/metabolism , Carcinoma/pathology , Dogs , Immunohistochemistry/veterinary , Jaw Neoplasms/metabolism , Jaw Neoplasms/pathology , Keratins/metabolism , Male , Vimentin/metabolism
15.
J Vet Med Sci ; 74(8): 1045-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22446404

ABSTRACT

Extraskeletal myxoid chondrosarcoma was found in a five-month-old male Irish setter dog. At necropsy, the largest mass, measuring 15 × 13 × 13 cm, was found in the right caudal lobe of the lung, and metastatic small masses were observed in multiple organs. Microscopically, the tumor comprised mainly atypical mesenchymal cells and myxoid stroma, which stained positively with Alcian blue. Immunohistochemically, the tumor cells stained positively for vimentin, S-100 protein, neuron-specific enolase, calretinin, and chromogranin A. Ultrastructurally, the cytoplasm of the tumor cells was comprised abundant rough endoplasmic reticulum, mitochondria, Golgi complex, free ribosomes and short irregular microvillous processes extending from the cytoplasm. Based on these pathological findings, this tumor was diagnosed as extraskeletal myxoid chondrosarcoma.


Subject(s)
Chondrosarcoma/veterinary , Dog Diseases/pathology , Lung Neoplasms/veterinary , Neoplasms, Connective and Soft Tissue/veterinary , Animals , Chondrosarcoma/pathology , Dogs , Lung Neoplasms/pathology , Male , Neoplasms, Connective and Soft Tissue/pathology
16.
J Vet Med Sci ; 74(6): 787-90, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22214863

ABSTRACT

Traumatic neuroma of the cervical spinal cord was diagnosed in a 14-year-old male mixed-breed dog. A gross view showed two intradural extramedullary masses, measuring 1 and 0.6 cm in length and 0.7 and 0.4 cm in diameter, attached to the left side of the spinal cord at the level of the sixth and seventh cervical vertebrae. Microscopically, the cervical spinal masses comprised interlacing fascicles of axons and Schwann cells surrounded by collagenous stroma. Immunohistochemically, the fascicles were stained positively for neurofilament and S-100 proteins. Ultrastructurally, variably sized myelinated fibers and onion bulb-like structures were observed. To our knowledge, this is the first report of a traumatic neuroma in the cervical spinal cord of a dog.


Subject(s)
Cervical Vertebrae/pathology , Dog Diseases/pathology , Neuroma/veterinary , Spinal Cord Neoplasms/veterinary , Animals , Dogs , Fatal Outcome , Immunohistochemistry/veterinary , Male , Nerve Fibers, Myelinated/ultrastructure , Neuroma/pathology , S100 Proteins/metabolism , Spinal Cord Neoplasms/pathology
17.
Virus Res ; 165(1): 34-45, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22248643

ABSTRACT

Street rabies viruses are field isolates known to be highly neurotropic. However, the viral elements related to their pathogenicity have yet to be identified at the nucleotide or amino acid level. Here, through 30 passages in mouse neuroblastoma NA cells, we have established an attenuated variant of street rabies virus strain 1088, originating from a rabid woodchuck followed by 2 passages in the brains of suckling mice. The variant, 1088-N30, was well adapted to NA cells and highly attenuated in adult mice after intramuscular (i.m.) but not intracerebral (i.c.) inoculations. 1088-N30 had seven nucleotide substitutions, and the R196S mutation of the G protein led to an additional N-glycosylation. Street viruses usually possess one or two N-glycosylation sites on the G protein, 1088 has two, while an additional N-glycosylation site is observed in laboratory-adapted strains. We also established a cloned variant 1088-N4#14 by limiting dilution. Apart from the R196S mutation, 1088-N4#14 possessed only one amino acid substitution in the P protein, which is found in several field isolates. 1088-N4#14 also efficiently replicated in NA cells and was attenuated in adult mice after i.m. inoculations, although it was more pathogenic than 1088-N30. The spread of 1088-N30 in the brain was highly restricted after i.m. inoculations, although the pattern of 1088-N4#14's spread was intermediate between that of the parental 1088 and 1088-N30. Meanwhile, both variants strongly induced humoral immune responses in mice compared to 1088. Our results indicate that the additional N-glycosylation is likely related to the reduced pathogenicity. Taken together, we propose that the number of N-glycosylation sites in the G protein is one of the determinants of the pathogenicity of street rabies viruses.


Subject(s)
Glycoproteins/metabolism , Rabies virus/metabolism , Rabies virus/pathogenicity , Rabies/virology , Viral Proteins/metabolism , Amino Acid Motifs , Amino Acid Sequence , Animals , Base Sequence , Cell Line, Tumor , Down-Regulation , Female , Glycoproteins/chemistry , Glycoproteins/genetics , Glycosylation , Humans , Marmota/virology , Mice , Molecular Sequence Data , Rabies virus/genetics , Serial Passage , Viral Proteins/chemistry , Viral Proteins/genetics , Virulence , Virus Cultivation
18.
PLoS One ; 6(10): e26388, 2011.
Article in English | MEDLINE | ID: mdl-22043319

ABSTRACT

A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (λmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (λmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues.


Subject(s)
Opsins/physiology , Photoreceptor Cells , Ultraviolet Rays , Animals , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Humans , Membrane Proteins , Mice , Photic Stimulation , Retinaldehyde , Tissue Distribution
19.
Jpn J Infect Dis ; 64(6): 463-72, 2011.
Article in English | MEDLINE | ID: mdl-22116324

ABSTRACT

The central nervous system (CNS) tissue of mice infected with the CVS-11 strain of rabies virus (RABV) was subjected to gene expression analysis using microarray and canonical pathway analyses. Genes associated with innate immunity as well as inflammatory responses were significantly up-regulated, corroborating with the previous findings obtained using attenuated viruses that did not induce a fatal outcome in infected mice. Histopathological examination showed that neurons in the cerebellum had undergone apoptosis. Although the extent of Fas ligand up-regulation was not so prominent, perforin and granzyme genes were highly expressed in the CNS of mice infected with CVS-11. The presence of perforin and granzymes both in the Purkinje cells and CD3 T lymphocytes strongly suggested that apoptosis of the former cells was induced by the latter cells.


Subject(s)
Central Nervous System/immunology , Central Nervous System/virology , Gene Expression Regulation , Immunity, Innate , Rabies virus/immunology , Rabies/immunology , Animals , Apoptosis , Cell Line , Cerebellum/pathology , Female , Gene Expression Profiling , Histocytochemistry , Humans , Mice , Mice, Inbred C57BL , Microarray Analysis , Neurons/pathology , Rabies/pathology , Rabies virus/pathogenicity , Reverse Transcriptase Polymerase Chain Reaction
20.
Photochem Photobiol Sci ; 9(11): 1498-504, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20886157

ABSTRACT

In response to ambient light levels, many lower vertebrates darken or lighten their body colors by regulating dispersion or aggregation, respectively, of melanin granules (melanosomes) in the melanophore. This physiological reaction is mediated by photoreception in the eyes, the pineal gland, the deep brain and the melanophores themselves, depending on species and their developmental stages. In this study, we established a method for quantitative measurement of the light-induced body color change in zebrafish larvae. From 2 days post-fertilization (dpf), the dermal melanophores responded to light illumination, but the response patterns and temporal profiles changed across the developmental stages. At 2 dpf, light illumination on larvae induced a relatively fast dispersion of the pigments in the melanophores, whereas continuous illumination additionally caused a delayed pigment aggregation at 3 dpf or later stages. Removal of the eyes abolished the light-dependent pigment aggregation but not the pigment dispersion at 5 dpf, while the pigment dispersion at 2 dpf was retained even in the isolated tail. These results suggest that the pigment dispersion is triggered by photoreception intrinsic to the melanophores and that the pigment aggregation is mediated by photoreception in the eyes. The monitoring system developed in this study will be useful to understand the neural mechanisms underlying the body color change depending on the ocular system. We also discussed the putative role(s) of opsin-type photoreceptive molecules in the light-induced body color change of the larval zebrafish.


Subject(s)
Larva/growth & development , Light , Microscopy/instrumentation , Zebrafish/growth & development , Animals , Color , Equipment Design , Melanophores/metabolism , Melanosomes/metabolism
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