シシンケイ サイセイ リョウホウ ノ ミライ

The optic nerve is a part of the central nervous system （CNS） and convey visual signals from the retina along their axons to the brain. Axonal damage can be induced by trauma, ischemia or in glaucoma, the most common cause of blindness in Japan. Like other CNS axons, the optic nerve has a very limited regenerative capacity. However, recent advances in research have revealed that combinational treatments, for example, overcoming the inhibitory environment of the glial scar and activating the intrinsic growth program, yield robust optic nerve regeneration. In addition, we revealed that overexpression of dedicator of cytokinesis 3 （Dock3）, one of the atypical Rho-guanine nucleotide exchange factors （Rho-GEFs）, plays important roles in promoting optic nerve regeneration. In response to the brain-derived neurotrophic factor （BDNF）, Dock3 activates multiple pathways that stimulate both actin polymerization and microtubule assembly, which are processes involved in neuroregeneration. Furthermore, Dock3 prevents glaucomatous retinal degeneration by suppressing both glutamate neurotoxicity and oxidative stress, suggesting that Dock3 signaling is a potential therapeutic target for both optic nerve regeneration and retinal neuroprotection. Based on our current knowledge, a combinatory approach including stimulation of Dock3 signalling may be effective for the treatment of complex diseases such as glaucoma, and this type of strategy may be available for future regeneration therapy using induced pluripotent stem （iPS） cells

<ORIGINAL REPORT>IMMUNOHISTOCHEMICAL STUDIES ON LACTATE DEHYDROGENASE SUBUNITS IN LUNG CANCER CELLS

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました。Immunohistochemical distribution of lactate dehydrogenase (LDH) subunits in human lung cancer cells were studied using fluorescent antibody technique. Both in cytological and histological specimen, specific fluorescence of LDH-H and LDH-M were seen in the cytoplasm of cancer cells, and in most cases no remarkable difference could be demonstrated between the distribution of H and M subunit. But in some cases specific fluorescence of M-subunit was stronger than that of H-subunit. The fluorescence of M-subunit was demonstrated as fine granules diffusely in the cytoplasm. On the other hand the fluorescence of H-subunit was rather localized and demonstrated as rather coarse granules. And this observation was discussed

Delayed Onset of Experimental Autoimmune Encephalomyelitis in Olig1 Deficient Mice

BACKGROUND: Olig1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG)-induced EAE in Olig1(-/-) mice is significantly slower than wide-type (WT) mice (19.8 ± 2.2 in Olig1(-/-) mice and 9.5 ± 0.3 days in WT mice). In addition, 10% of Olig1(-/-) mice did not develop EAE by the end of the observation periods (60 days). The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/-) mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/-) mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/-) mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS

A Case Report of Atypical Spindle Cell Lipomatous Tumor of the Tongue

Herein, we report a case of atypical spindle cell lipomatous tumor (ASCLT) on both sides of the tongue in a 74-year-old male patient. The patient was referred to our department for treatment of the masses in the tongue. Several elastic soft indolent masses were detected during the first examination. The masses were well defined, and their consistency was similar to that of adipose tissues. No signs of induration were observed in the surrounding tissues. The patient was not aware of the masses, which were only detected during his visit at the dental clinic that referred him to our institution. Thus, the onset of the masses remains unknown. ASCLT was identified via histopathological examination. Then, tumor excision was performed under general anesthesia. Thirteen months after surgery, the condition of the patient was good, and signs of local recurrence or postoperative metastasis were not observed

2種類の正常眼圧緑内障モデルマウスに対するN-アセチルシステインの網膜変性抑制効果の違い

N-acetylcysteine (NAC) is widely used as a mucolytic agent and as an antidote to paracetamol overdose. NAC serves as a precursor of cysteine and stimulates the synthesis of glutathione in neural cells. Suppressing oxidative stress in the retina may be an effective therapeutic strategy for glaucoma, a chronic neurodegenerative disease of the retinal ganglion cells (RGCs) and optic nerves. Here we examined the therapeutic potential of NAC in two mouse models of normal tension glaucoma, in which excitatory amino-acid carrier 1 (EAAC1) or glutamate/aspartate transporter (GLAST) gene was deleted. EAAC1 is expressed in retinal neurons including RGCs, whereas GLAST is mainly expressed in Müller glial cells. Intraperitoneal administration of NAC prevented RGC degeneration and visual impairment in EAAC1-deficient (knockout; KO) mice, but not in GLAST KO mice. In EAAC1 KO mice, oxidative stress and autophagy were suppressed with increased glutathione levels by NAC treatment. Our findings suggest a possibility that systemic administration of NAC may be available for some types of glaucoma patients

Ripasudil Promotes Neuroprotection

PURPOSE. To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma. METHODS. Topical administration (5 μL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, the measurement of intraocular pressure (IOP), and histopathology analyses were performed at 5, 8, and 12 weeks old. Retrograde labeling of retinal ganglion cells (RGCs), immunoblot, and immunohistochemical analyses of phosphorylated p38 mitogen-activated protein kinase (MAPK) in the retina were performed at 8 weeks old. RESULTS. Topical ripasudil ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old. Ripasudil reduced IOP and strongly suppressed the phosphorylation of p38 MAPK that stimulates RGC death in EAAC1 KO mice. CONCLUSIONS. These results suggest that, in addition to IOP reduction, ripasudil prevents glaucomatous retinal degeneration by neuroprotection, which is achieved by suppressing cell-death signaling pathways