Spinosin Attenuates Alzheimer’s Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity

Hippocampal synaptic dysfunction is a hallmark of Alzheimer’s disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

β-Amyrin Ameliorates Alzheimer’s Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus

Alzheimer’s disease (AD) is a progressive and most frequently diagnosed neurodegenerative disorder. However, there is still no drug preventing the progress of this disorder. β-Amyrin, an ingredient of the surface wax of tomato fruit and dandelion coffee, is previously reported to ameliorate memory impairment induced by cholinergic dysfunction. Therefore, we tested whether β-amyrin can prevent AD-like pathology. β-Amyrin blocked amyloid β (Aβ)-induced long-term potentiation (LTP) impairment in the hippocampal slices. Moreover, β-amyrin improved Aβ-induced suppression of phosphatidylinositol-3-kinase (PI3K)/Akt signaling.LY294002, a PI3K inhibitor, blocked the effect of β-amyrin on Aβ-induced LTP impairment. In in vivo experiments, we observed that β-amyrin ameliorated object recognition memory deficit in Aβ-injected AD mice model. Moreover, neurogenesis impairments induced by Aβ was improved by β-amyrin treatment. Taken together, β-amyrin might be a good candidate of treatment or supplement for AD patients.

Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor / 中国天然药物

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.

Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor / 中国天然药物

Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.

Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission

Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 μg/ml) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol.

Secondary Superior Oblique Overaction after Inferior Oblique Muscle Myectomy in a Patient Misdiagnosed with Inferior Oblique Muscle Overaction

PURPOSE: To report a case of superior oblique muscle tenotomy in a patient with suspected bilateral inferior oblique muscle overaction. The patient showed secondary superior oblique muscle overaction and inferior oblique muscle underaction after inferior oblique muscle myectomy. CASE SUMMARY: The patient showed V-pattern exotropia with suspected bilateral inferior oblique muscle overaction. After bilateral lateral rectus muscle recession with bilateral inferior oblique muscle myectomy, the patient showed secondary esotropia and inferior oblique underaction. After the surgery, progressive secondary superior oblique muscle overaction continued and finally, a superior oblique muscle tenotomy was performed. After the superior oblique muscle tenotomy, the superior oblique muscle overaction was corrected but the inferior oblique muscle underaction continued. CONCLUSIONS: After an inferior oblique muscle myectomy, secondary superior oblique muscle overaction can develop. Thus, caution should be taken in diagnosing inferior oblique muscle overaction in patients who show minimally inferior oblique muscle overaction as well as the surgical methods chosen.

Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells

In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the downregulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-kappaB activation in human melanoma cells.

Factors Mediating Effects on the Retinal Nerve Fiber Layer Thickness in Normal Children

PURPOSE: The peripapillary retinal nerve fiber layer thickness (RNFL) was measured in normal children using optical coherence tomography (OCT), and the effect of various factors on the RNFL thickness was examined. METHODS: From April 2006 to January 2007, the RNFL thickness of 74 normal children (148 eyes) between the ages of 4 and 17 years old was measured by OCT, and the effect of factors such as age, gender, refractive error, C/D ratios, cooperation, and laterality on the peripapillary RNFL thickness was analyzed. RESULTS: The mean age of the patients was 10.2 years (4~17 years), and the mean peripapillary RNFL thickness was 106.3+/-12.8 micrometer. As to the thickness of the different peripapillary locations, the superior side was thickest (135.3+/-20.6 micrometer), followed in order by the inferior side (130.9+/-23.0 micrometer), the temporal side (86.3+/-18.9 micrometer), and the nasal side (71.9+/-20.8 micrometer). The refractive error was correlated positively with RNFL thickness (r=0.277, p=0.001), and age correlated negatively with RNFL thickness (r=-0.194, p=0.018). CONCLUSIONS: RNFL thickness in normal children increases as the refractive error becomes hyperopic and decreases with age. The data about RNFL thickness of normal children obtained in this study may provide useful information for an early diagnosis of pediatric neuroophthalmologic disease and for monitoring its progression.

A Case of Vogt-Koyanagi-Harada(VKH)Syndrome Combined with Choroidal Detachment in Diatetic Nephropathy Patient

VKH syndrome is a symptom complex having prodromal systemic manifestations, bilateral uveites and exudative retinal detachment. It has not been known clearly whether it is relelated to DM or not. We experienced a 43-year old man complaining of acutely decreased visual acuity in both eyes with bilateral choroidal detachment. He has been diabetic for 5 years in uncontrolled state. He was diagnosed to have VKH syndrome and was treated with local steroid injection with visual improvement. So we present this case with review of literatures.

Pupillary Capture of Posterior Chamber Lens

Puillary capture in an unusual complication of posterior chamber intraocuIar lens (PCL) implantation and may occur in the early or late postoperative period. An analysis of clinical records was made in 27 pupillary capture cases receiving PCL from Jan 1, 1986 to Mar. 31, 1990. Twenty-two cases (81.5%) were male, and five cases (18.5%) were female. Among the captured PCL, 6.0mm optic and 13.5mm length PCLs were most commonly implanted. All PCLs used in the study had lO degrees angulation of the IOL loops and asymmetric fixation of loop was noted in 5.9% of all pupillary catpure cases. The interval between cataract operation and pupillary capture was variable but most cases (81.5%) of pupillary capture were developed within one year after operation. The subjective symptoms and signs of pupillary capture were decreased vision, glare, double vision, conjunctival injection, tearing and discomfortness while 12 cases (44.4%) had no subjectIve symptoms The reposition of pupillary capture was successfully done by using mydriatics and miotics in 15 of 27 cases (55.6%) and surgical correction was needed in only 2 cases. The recurrence was developed in 53.3% of cases that were corrected with mydriatics Complictions of pupillary capture were iridocapsular or iridolenticular adhesion, atrophy and depigmentation of iris, transient iritis, and pupillary distortion.