본 연구는 서로 다른 운동유형이 당뇨처치 그룹의 베타 아밀로이드, BDNF 및 인지기능에 미치는 영향을 알아보기 위하여 24마리의 C57BL/6 쥐를 당뇨처치를 하지 않은 그룹 6마리(통제그룹: 6)와 당뇨처치 그룹 18마리로 무작위 할당하여, 이를 다시 당뇨처치 그룹의 경우 통제그룹 6마리, 유산소 운동그룹 6마리, 저항운동 그룹 6마리로 나누었고 운동그룹은 8주간 주 5회 저강도로 각각 트레드밀 운동과 사다리 운동을 실시하였다. 그 결과 베타아밀로이드는 8주 후 당뇨처치 그룹의 통제그룹 (DM.G.)이 나머지 세 그룹에 비하여 높은 수준을 나타내었으나 통계적으로 유의한 차이는 나타나지 않았다. BDNF의 경우는 당뇨통제그룹이 나머지 세 그룹에 비하여 낮은 수준을 나타냈으며 통계적으로 유의한 차이를 나타냈다(p<.05). 인지기능을 알아보기 위한 Y-미로 검사에서도 당뇨통제 그룹이 나머지 세그룹에 비하여 낮은 수준을 보였으며 통계적으로도 유의한 차이를 나타냈다(p<.05).

본 연구는 알츠하이머(Alzheimer’s disease: AD) 형질전환 생쥐를 대상으로 저항성 운동 (resistance exercise: RE)이 해마의 베타 아밀로이드(β-amyloid: Aβ) 단백질 대사, 신경세포사멸 및 인지기능에 미치는 영향을 확인하는데 목적이 있다. AD 비 형질전환 생쥐(non-transgenic: non-tg, n=14) 와 형질전환 생쥐(transgenic: Tg, n=14)를 무선 배정하여 비 형질전환 생쥐 대조군 (non-tg-control: NTC, n=7), 비 형질전환 생쥐 저항성 운동군(non-tg-RE: NTRE, n=7), 형질전환 대조군(tg-control: TC, n=7) 및 형질전환 저항성 운동군(tg-RE: TRE, n=7)으로 구분하였다. RE는 특수 제작한 사다리 저항성 운동 기구를 사용하여 점진적으로 set 수를 증가시켜 총 8주간 실시하였다. 운동 후 인지기능 능력을 평 가하기 위한 수중미로검사와 Aβ 단백질 대사, 신경세포사멸 지표 및 SIRT1/PGC-1α 단백질 발현 수준 을 확인하였다. 수중미로검사 결과 거리와 시간 모두 TC 집단에서 유의하게 증가 되었지만 RE를 실시한 TRE 집단에서 거리와 시간이 감소 되어 인지능력이 개선된 것으로 확인되었다. 또한, TC 집단에서 증가 된 Aβ 단백질 발현은 RE를 통해 감소하는 것으로 나타났다. 신경세포사멸 관련 단백질인 Bcl-2/Bax ratio는 TC 집단에서 유의하게 감소되어 신경세포사멸이 증가 된 것으로 나타났지만 RE는 Bcl-2/Bax ratio을 증가시켜 신경세포사멸을 감소시킨 것으로 확인되었다. TC 집단에서 증가된 BACE1 및 ROCK1 과 감소된 ADAM10과 RARβ 단백질 발현은 RE를 통해 감소되거나 증가 된 것으로 나타났고, SIRT1/ PGC-1α 단백질 발현은 TC 집단에서 감소 되었지만 RE를 통해 증가 된 것으로 나타났다. 따라서 8주간 의 RE는 AD의 병리학적 특징인 Aβ 단백질 발현을 감소시키고 관련 생성 기전들을 조절하여 (SIRT1/PGC-1α 기전 활성, 아밀로이드 생성기전 억제, 비-아밀로이드 생성기전 활성) 신경세포사멸 억제시키고 결과적으로 인지기능을 개선 시킬 수 있는 효과적인 운동 방법이라고 생각된다.

본 연구는 노루궁뎅이버섯 균사체로 발효시킨 엄나무 추출물의 항산화 및 항아밀로이드 활성을 알아보고자 하였다. 항산화 활성은 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical 소거 측정법을 사용하여 관찰하였다. 엄나무 추출물(KP), 노루궁뎅이버섯 균사체 추출물(HE), 엄나무 발효물(KP-HE)에서 모두 라디칼 소거활성이 관찰되었다. 그러나 KP-HE가 KP와 HE에 비해서 더 높은 소거 활성을 갖는 것으로 관찰되었다. KP-HE는 peroxyl radical에 의한 DNA의 산화적 손상을 억제하였다. 알츠하이머병 (Alzheimer's disease: AD)과 관련 있는 Aβ1-42의 응집에 KP, HE, KP-HE가 어떤 영향을 미치는 지를 알아보았다. KP와 HE는 Aβ1-42의 응집에 거의 영향을 미치지 않았고 KP-HE는 Aβ1-42의 응집을 효과적으로 억제하였다. 또한 Aβ1-42에 의한 신경세포 사멸에 엄나무 발효물을 300 μg/mL 농도로 전 처리한 세포생존율은 20.3% 높게 증가되었다. 또한 엄나무 발효물을 50 μg/mL 농도로 처리했을 경우 세포 내 ROS의 축적이 유의적으로 감소되었다. 결론적으로 본 연구에서 관찰된 결과들을 통해 엄나무 발효물은 항산화 및 항아밀로이드 활성을 가지는 것으로 확인되었다. 따라서 엄나무 발효물은 알츠하이머병과 같은 퇴행성 뇌질환을 예방할 수 있는 식품소재로 이용될 수 있을 것으로 사료된다.

Amyloid-β protein (Aβ) is known to increase free radical production in neuronal cells, leading to cell death by oxidative stress. The purpose of this study was to evaluate the protective effects of PineXol® on Aβ25-35 induced neuronal cell death. Rat pheochromocytoma (PC-12) cells were pre-treated with 100 μg/mL of PineXol® for 2 h. The cells were exposed to single dose of 30 μM Aβ25-35 for 24 h. Cell death was assessed by a cell count kit-8 (CCK-8) assay, lactate and dehydrogenase (LDH) release assay. An Apoptotic process was analyzed by a protein expression of the Bcl-2 family using western blotting. Cell viability increased in PC-12 cells treated with both Aβ25-35 and PineXol®, compared to the control group. PineXol® induced a decrease of the Bcl-2 protein expression (p<0.05), while Bax and Sod1 increased (p<0.05), indicating attenuation of Aβ25-35 induced apoptosis. These results suggest that PineXol® may be a good candidate for the prevention of Alzheimer’s disease(AD).

Alzheimer’s disease (AD), a progressive neurodegenerative disorder that deprives the patient of memory, is associated mainly with extracellular senile plaque induced by the accumulation of amyloid β protein (Aβ). Silybum marianum (Asteraceae; SM) is a medicinal plant that has long been used in traditional medicine as a hepatoprotective remedy owing to its antioxidant and anti-inflammatory activities. The present study examined the methanol extract of the aerial parts of SM for neuroprotection against Aβ (25-35)-induced neuronal death in cultured rat cortical neurons to investigate a possible therapeutic role of SM in AD. The primary cortical neuron cultures were prepared using embryonic day 15 to 16 SD rat fetuses. Cultured cortical neurons exposed to 10 μM Aβ (25-35) for 36 h underwent neuronal cell death. At 10 and 50 μg/mL, SM prevented Aβ (25-35)-induced neuronal cell death and apoptosis in cultured cortical neurons. Furthermore, SM inhibited the Aβ (25-35)-induced decrease in anti-apoptotic protein, Bcl-2, and the increase in the proapoptotic proteins, Bax and active caspase-3. Cultured cortical neurons exposed to 1 mM N-methyl-D-aspartate (NMDA) for 14 h induced neuronal cell death. SM (10 and 50 μg/mL) prevented NMDA-induced neuronal cell death. These results suggest that SM inhibited Aβ (25-35)-induced neuronal apoptotic death via inhibition of NMDA receptor activation and that SM has a possible therapeutic role in preventing the progression of neurodegeneration in AD.

Serum amyloid A (SAA) is an acute phase protein with pro-inflammatory cytokine-like properties. Recent studies have revealed that SAA promotes γδT cell to produce IL-17 and T helper 17 (Th17) cells differentiation and function. In this study, we established the hepatic SAA1 overexpressed transgenic mice (TG). In this mouse, IL-17 was significantly increased in conditional state by γδT cell. We revealed that SAA1 mediated IL-17 producing from γδT cell is dependent on TLR2. Moreover we immunized SAA1 TG mice with Complete Freund’s adjuvant (CFA), which is well-known inducer of Th1 response and IFN-γ. We observed increased IL-17 secretion with increased Th17 cells and decreased IFN-γ, which is contrast to wild type mice (WT). In addition, we showed that locally increased transforming growth factor- β (TGF-β) followed by Th17 cells polarization might involve in Th17 cell maintenance by suppressing the expression of T-bet, a key transcription factor for the differentiation of T helper 1 (Th1) cells. These data demonstrate that SAA1 represent potent endogenous protein that drives IL-17 induced inflammation by γδT cell partially through TLR2 and by Th17 cell. Also these increased IL-17 response maintained by TGF-β Smad2/3 signaling. Therefore we could say that SAA is central player in IL-17 related inflammatory response.

Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.

disease is a characterized by cognitive impairment, progressive neurodegeneration and formation of amyloid-β (Aβ)-containing plaques and neurofibrillary tangles. In progress of disease, inflammation plays major role to lead the neuronal death. Previously Serum amyloid A (SAA1), one of the acute-phase proteins, was examined and found that this liver derived protein pass through the brain blood barrier (BBB). By making double transgenic mice through the crossing over APP c105 mice, produce amyloid beta1-42 in brain as a pathogen, and SAA1 overexpression mice confirm the SAA exacerbate inflammation that triggered by amyloid beta accumulation in brain. Followed behavior test also shows double transgenic mice have more damage in memory than the APP mouse that only designed to express the amyloid beta 1-42.

To investigate the in vivo cognitive effects of syringic acid(SA), Y-maze and passive avoidance tests were performed in amyloid-β(Aβ)-induced cytotoxicity. Learning and memory impairment by Aβ neurotoxicity was partially recovered in Institute of Cancer Research(ICR) mice orally administered SA(10mg/kg of body weight). The SA treated group showed an inhibitory effect on acetylcholinesterase(AChE) that was extracted from mice brain tissue after in vivo tests. Aβ-induced oxidative stress was also examined by malondialdehyde(MDA) and 2',7,-dichlorofluorescein diacetate(DCF-DA) assays, and lipid peroxidation of brain homogenates and cellular oxidative stress were reduced by SA. In cell viability assays using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide(MTT), lactate dehydrogenase(LDH) leakage, and caspase 3/7 activity, the SA treated group showed relatively effective protection against Aβ-induced neurotoxicity compared to the others. Consequently, these results suggest that SA in black soybean seed coat extract might improve cognitive function because of its neuronal cell protective effects against oxidative stress and the inhibitory effect of AChE as a cholinergic enzyme.

The present study was carried out to establish an animal model, displaying long-term learning and memory dysfunction, since single intracerebroventricular (icv) injection of amyloid β peptide (Aβ) causes a short-term memory impairment. Male ICR mice were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 1% corn oil and 0.5% cholic acid, and 1 week later, icv injected with Aβ_1-42 (5 μg/head). Learning/ memory function was assessed via passive avoidance performances 1 day and 2, 4, and 6 weeks after Aβ_1-42 injection, in addition to blood biochemical analyses for lipid profiles and hepatic function. Total cholesterol, lowdensity lipoproteins and hepatic dysfunction parameters markedly increased, while high-density lipoproteins were reduced following HCD feeding. Whereas single injection of Aβ induced temporary memory loss 1 day after administration, exhibiting full recovery after 2 weeks, Aβ treatment in combination with HCD feeding lasted the learning/memory impairment up to 6 weeks. Therefore, it is suggested that hypercholesterolemia augments Aβ-induced memory loss, and that Aβ injection plus HCD feeding could be a long-term memorydeficit model suitable for long-term treatment with drugs or stem cells.

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta (Aβ) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced Aβ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of Aβ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

Background : Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss, cognitive impairment and personality defects accompanied by diffuse structural abnormalities in the brain. The major pathological hallmarks of AD include beta amyloid (Aß) protein deposition, presence of neurofibrillary tangles and neurodegeneration of cholinergic neurons. Aß, a 39-43 amino acid proteolytic fragment of amyloid precursor protein, is the major constituent of the senile plaques. Rice bran, the major byproduct of the rice milling industry, is the source of a high quality vegetable oil. Rice bran oil (RBO) has attracted much medicinal attention for its strong hypocholesterolemic properties because of its balanced fatty acid composition and high levels of antioxidant phytochemicals such as oryzanols, tocopherols and tocotrienols. The present study aims to investigate the protective effect of RBO against Aß (25-35)-induced neurotoxicity in in vitro and in vivo. Methods and Results : Memory impairment was produced by intracerebroventricular (i.c.v) microinjection of 15 nmol Aß (25-35) and measured by passive avoidance test in ICR mice. Glutathione concentration, lipid peroxidation rate and acetylcholine esterase activity were measured in mice brain. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), inflammatory factors, and anti-apoptotic and pro-apoptotic proteins in mice brains were detected by Western blot. Cerebral cortical neuronal cells were cultured from 15-days-old fetus. Cortical neurons were incubated with 10 μM Aß (25-35) for 36 h. Cell viability was measured by MTT assay. Chronic treatments of RBO (0.1-1 ml/kg, 8 days, p.o.) protected against memory impairment induced by Aß (25-35). Depletion of glutathione level, lipid peroxidation and increased acetylcholine esterase activity by the treatment with Aß (25-35) were inhibited by administration of RBO. The increase of phosphorylated MAPKs, inflammatory factors, and proapoptotic proteins and the decrease of antiapoptotic protein in Aß (25-35)-administered mice brain were significantly inhibited by treatment with RBO. RBO (0.1-5ul/ml) inhibited 10μM Aß (25-35)-induced neuronal cell death in cultured cortical neurons. Conclusion : The present study suggests the role of RBO as a promising therapeutic for neurodegenerative diseases like AD and stroke.

The present study investigated an ethanol extract (SSB) of a mixture of three medicinal plants of Vitisamurensis, Aralia cordata, and Glycyrrhizae radix for possible neuroprotective effects on neurotoxicity induced byAmyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cor-tical neurons to 15μM Aβ (25-35) for 36h induced neuronal apoptotic death. At 1-30㎍/㎖, SSB inhibited neuronal death,elevation of intracellular calcium concentration ([Ca²+]i), and generation of reactive oxygen species (ROS) induced by Aβ(25-35) in cultured cortical neurons. Memory impairment and increase of acetylcholinesterase activity induced by intra-cerebroventricular injection of mice with 16nmol Aβ (25-35) was inhibited by chronic treatment with SSB (25, 50 and100㎎/㎏, p.o., for 8 days). From these results, it is suggested that antidementia effect of SSB is due to its neuroprotectiveeffect against Aβ (25-35)-induced neurotoxicity and that SSB may have a therapeutic role in preventing the progression ofAlzheimer’s disease.

본 연구에서는 도라지 추출물에 대한 세포 독성을 확인하였으며, Aβ에 의한 PC12 세포 독성에 대한 보호효과를 관찰하였다. 또한 도라지 추출물과 도라지 추출물 연양갱을 4주간 강제 경구 투여하여 Morris 수중미로시험에서 도달지점까지의 도달시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 모두에서 유의하게 감소하였다. 이와 유사하게 수동회피시험에서도 자극이 있는 어두운 방을 나오는 시간이 도라지 추출물 및 도라지 추출물 연양갱 투여에 의해서 현저하게 감소하였다. 따라서 도라지 추출물 및 도라지 추출물 연양갱은 인지능 개선에 도움을 줄 것으로 생각된다.

The present study investigated an ethanol extract of Chaenomeles sinensis fruit (CSF) for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10μM Aβ (25-35) for 36 h induced neuronal apoptotic death. At 0.1-10μg/ml, CSF inhibited neuronal death, elevation of intracellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) induced by Aβ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of mice with 15 nmol Aβ (25-35) was inhibited by chronic treatment with CSF (10, 25 and 50 mg/kg, p.o. for 7 days) as measured by a passive avoidance test. CSF (50 mg/kg) inhibited the increase of cholinesterase activity in Aβ (25-35)-injected mice brain. From these results, we suggest that the antidementia effect of CSF is due to its neuroprotective effect against Aβ (25-35)-induced neurotoxicity and that CSF may have a therapeutic role for preventing the progression of Alzheimer's disease.

The present study investigated an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcumalongae radix, Phellinus linteus, and Scutellariae radix for possible neuroprotective effects on neurotoxicity induced by amyloid βprotein (Aβ) (25-35) in cultured rat cortical neurons and antidementia activity in mice. Exposure of cultured cortical neurons to10µM Aβ (25-35) for 36h induced neuronal apoptotic death. At 1-50㎍/㎖, HS0608 inhibited neuronal death, elevation of intra-cellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) induced by Aβ (25-35) in primary cul-tures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of ICR mice with 15 nmol Aβ (25-35) wasinhibited by chronic treatment with HS0608 (25, 50 and 100㎎/㎏, p.o. for 7 days) as measured by a passive avoidance test. Fromthese results, we suggest that the antidementia effect of HS0608 is due to its neuroprotective effect against Aβ (25-35)-inducedneurotoxicity and that HS0608 may have a therapeutic role in preventing the progression of Alzheimer’s disease.