Hidenori Horie

Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus

We examined the expression of galectin-1, an endogenous lectin with one carbohydrate-binding domain, in the adult mouse hippocampus after systemic kainate administration. We found that the expression of galectin-1 was remarkably increased in activated astrocytes of the CA3 subregion and dentate gyrus of the hippocampus, and in nestin-positive neural progenitors in the dentate gyrus. Quantitative reverse transcription PCR (RT-PCR) analysis revealed that the galectin-1 mRNA level in hippocampus began to increase 1 day after kainate administration and that a 13-fold increase was attained within 3 days. Western blotting analysis confirmed that the level of galectin-1 protein increased to more than three-fold a week after the exposure. We showed that isolated astrocytes express and secrete galectin-1. To clarify the significance of the increased expression of galectin-1 in hippocampus, we compared the levels of hippocampal cell proliferation in galectin-1 knockout and wild-type mice after saline or kainate administration. The number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells detected in the subgranular zone (SGZ) of galectin-1 knockout mice decreased to 62% with saline, and to 52% with kainate, as compared with the number seen in the wild-type mice. Most of the BrdU-positive cells in SGZ expressed doublecortin and neuron-specific nuclear protein, indicating that they are immature neurons. We therefore concluded that galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the hippocampus.

The Galectin-1 level in serum as a novel marker for stress

Galectin-1(Gal-1), a carbohydrate-binding protein with an affinity for β-galactoside, is widely expressed in various normal and pathological tissues and it also plays an important role in regulating immune cell homeostasis and tumorigenesis. This study investigated the effects of restraint stress on serum Gal-1 by Western blot analyses and enzyme-linked immunosorbent assays. The Gal-1 levels of the restraint-stress group were significantly higher than those of the control group. However, this increase by stress was not obvious in adolescent rats. The pattern of these changes was similar to that of corticosterone. Furthermore, this Gal-1 increase in the serum was prevented by pre-treatment with a neurotoxin 6-hydroxydopamine (6-OHDA), which destroys the noradrenergic nerve terminals. However, a bilateral adrenalectomy (ADX) had no effect on the Gal-1 increase. These results suggest that Gal-1 is a candidate stress marker protein and that the stress-induced increase of Gal-1 in serum is regulated by the sympathetic nervous system under stress conditions.

A role for galectin-1 in the immune response to peripheral nerve injury

Galectin-1 (Gal1) is a multi-functional protein that has key roles in organismal growth and survival. In the adult nervous system, Gal1 promotes axonal regeneration following peripheral nerve injury. Although the mechanism by which Gal1 promotes regeneration is unclear, previous reports suggested that Gal1 acts indirectly by activating macrophages. An appropriate response of macrophages is crucial for repair of injured nerves: these immune cells remove obstructive axon and myelin debris in the distal nerve. Here we establish a role for Gal1 in the accumulation of immune cells following peripheral axotomy. We used immunohistochemistry to visualize macrophages (F4/80) in wild-type (Lgals1(+/+)) and knockout (Lgals1(-/-)) mouse sciatic nerves following injury and/or manipulation of Gal1 levels. Density of F4/80 immunoreactivity, which peaks around 3 days post-injury, was decreased in Lgals1(+/+) nerves injected with Gal1 antibody. The typical injury-induced peak of macrophage/microglial density was delayed in the sciatic nerves and fifth lumbar dorsal root ganglia of Lgals1(-/-) mice relative to control mice. Injection of oxidized Gal1 into uninjured sciatic nerve promoted the accumulation of macrophages in Lgals1(+/+) nerves. Finally, we used transplants of sciatic nerve to uncover a compensatory mechanism in Lgals1(-/-) mice that allows for macrophage accumulation (albeit delayed and diminished) following axotomy. We conclude that Gal1 is necessary to direct the typical accumulation of macrophages in the injured peripheral nerve, and that Gal1 is sufficient to promote macrophage accumulation in the uninjured nerve of wild-type mice.

Training regimen involving cyclic induction of pupil constriction during far accommodation improves visual acuity in myopic children.

Purpose Myopia in school-age children has become increasingly prevalent in industrialized countries, especially in Asia. A large population of school-age children still suffers from low visual acuity. We have developed a novel, safe and noninvasive training method to activate a pupillary constriction response during far accommodation that results in improved visual acuity. Methods Myopic children (n = 95) were treated for 3-minute sessions up to twice a week for 12–106 weeks. We stimulated quick cycles of near/far accommodation by displaying a visual object on a LCD screen and moving the screen in cycles from a near (25 cm) to a far (70 cm) point and back, while keeping the retinal projection size and brightness of the object constant. Results Mechanistically, we noted pupillary constriction upon far accommodation in trained myopic children, which was not seen in normal subjects or in untrained myopic children. Eighty five percent (52/61) of trained myopic right eyes with two sessions weekly experienced improved visual acuity (VA) by more than 0.1 logMAR units with an average improvement of 0.30 ± 0.03 standard error of mean (SEM) logMAR units. With maintained training, most eyes’ improved VA stayed almost constant, for more than 50 weeks in the case of 12 long trained subjects. Conclusions This simple, short and safe accommodation training greatly improves the quality of vision in a large population suffering from refractive abnormalities.

Regeneration of optic nerve axons in zebrafish

The CNS of teleost fish is capable of spontaneous axon regeneration after nerve fiber injury. The mechanisms in neurons that allow successful axonal regeneration are not fully understood. Both extrinsic factors from the neuronal environment and intrinsic neuronal factors seem to play a role in successful nerve regeneration. Zebrafish retina is a useful model for the study of axonal promoting factors. In this study, we examined effects of conditioned media from neurons or cells on axonal regeneration from cultured zebrafish retinal explant. Neurite outgrowth from the explant retina was observed in the medium 10% FBS but not in the medium containing 1% FBS. However, conditioned medium from rat macrophages promoted axonal regeneration in 1% FBS up to the same level as in 10% FBS.

A novel device improves myopic visual acuity through pupil constriction during far accommodation

P2-e48 A novel device improves myopic visual acuity through pupil constriction during far accommodation Hidenori Horie1,2,3, Kenji Yuda4, Eiichi Ookawa5, Satoshi Hisahara5, Hiroshi Uozato6, Hiroko Horie2, Satomi Nakajima2, Kenkichi Tanioka7, Yuji Ohkawa7, Tomoki Matubara7, Wolfram Tetzlaff8 1 Brain & Oral Sciences, Kanagawa Dental College, Kanagawa, Japan; 2 TechnoMaster Co Ltd., Yokohama, Japan; 3 Adv. Inst. for Biol. Sci., Waseda University, Tokyo, Japan; 4 Kikuna Yuda Eye Clinic, Yokohama, Japan; 5 Healthcare Business Co., Matsushita Electric Ind. Co. Ltd., Yokohama, Japan; 6 Department of Ophthalmology & Visual Sciences, Kitasato University, Kanagawa, Japan; 7 NHK Sci. and Technical Res. Lab., Tokyo, Japan; 8 ICORD, University of British Columbia, Vancouver, Canada