S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
A study on the effects of phloroglucinol on the cognitive impairments and neuropathological changes in Alzheimers disease model
플로로글루시놀에 의한 알츠하이머병 모델에서의 인지 기능 개선 및 신경병변학적 변화에 대한 연구
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- Alzheimer’s disease; Cognitive impairment; Oxidative stress; Phloroglucinol; Synaptic plasticity
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의과학과, 2018. 2. 김혜선.
- Amyloid plaques and neurofibrillary tangles are known to be the major neuropathological hallmarks of Alzheimers disease (AD). Among the various causative factors involved in the pathogenesis of AD, oxidative stress has emerged as one of the important factors. Thus, antioxidant therapeutics could be a key treatment for AD. Phloroglucinol is a polyphenol that is a component of phlorotannins, sufficiently included in Ecklonia cava (E. cava). Phloroglucinol has been reported to exert antioxidant activities in various tissues. However, the effects of phloroglucinol in the central nervous system, especially in AD is remains. Here, I identified the therapeutic activity of phloroglucinol in vitro and in vivo AD models. Phloroglucinol inhibited the increase in ROS accumulation and ameliorated the decrease in expression of dendritic spine density/synaptic plasticity-related proteins induced by hydrogen peroxide or amyloid beta peptide (A) in neuronal cells. Furthermore, the stereotaxic injection or oral administration of phloroglucinol attenuated the impairments in cognitive function observed in 5X familial AD (5XFAD) mice. The 5XFAD mice treated with an oral dosage of phloroglucinol for 2 months showed a reduction in the number of amyloid plaques and in the protein level of BACE1, one of the major amyloid precursor protein (APP) that cleave enzymes together with y-secretase. Phloroglucinol also restored the reduction in dendritic spine density and mature form of spines in the hippocampus of the 5XFAD mice. In addition, phloroglucinol-administrated 5XFAD mice displayed lower protein levels of GFAP and Iba-1 and mRNA levels of TNF-αand IL-6 compared with vehicle-administered 5XFAD mice.
These results demonstrated that phlorogucinol alleviated neuropathological features and progression of AD in vitro and in vivo models. Thus, phloroglucinol has a therapeutic potential for AD treatment.