Effect of Ferulic Acid on Learning and Memory Impairment by the Repairing of Mitochondrial Fission-Fusion Imbalance in AD Mice
WANG Qian1, QIN Wei-wei2, ZHANG Jie-wen2*
1. Department of Neurology, Zhumadian Central Hospital, Zhumadian 463000, China; 2. Department of Neurology of Henan Province People��s Hospital, Zhengzhou 450000, China
Abstract��OBJECTIVE To discuss the effect of ferulic acid(FA) on learning and memory impairment and neuron protection by repairing the imbalance of mitochondrial fission-fusion dynamics in Alzheimer��s disease (AD) mice. METHODS The KM mice were randomly divided into normal control group (A group, n=10), model group (B group, n=10), positive control group (huperzine A tablets, C group, n=10) and low dose of FA group (D-low group, n=10), high dose of FA group (D-high group, n=10). Mice in B, C, D-low and D-high groups were built as AD model by injecting A��1-42 into the lateral ventricle. The learning and memory ability of mice were detected by Morris water maze test. The mRNA of dynamin-related protein 1 (Drp1) were detected by PCR. The AD related pathological proteins and mitochondrial fission-fusion proteins were detected by Western blot. The content and distribution of A�� was analyzed using immunofluorescence staining. RESULTS ��The escape latency of mice in D-high group was shorter than B group, but a little longer than A group (P<0.05). The swimming time in the 4th quadrant in D-high group was longer than B group (P<0.05), but as the same as A group (P>0.05). ��The mean expressions of Drp1, CaN subunit �� (CnA��), CnA�� mRNA in D-high group were lower than B group, but higher than A group (P<0.05). ��The mean expressions of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (Bace1), Tau46 and pS396 proteins in D-high group were lower than B group, but higher than A group (P<0.05).��The mean expressions of Drp1Ser637, CnA��, protein kinase A catalytic subunit c (PKAc), mitofusin gene 2(Mfn2) proteins in D-high group were basically identical with A group. ��The levels of A�� formation and accumulation in mice cortex and hippocampus of D-high group were less than B group. CONCLUSION It��s suggested that ferulic acid(FA) might repair pathological damage of Alzheimer��s disease by improving the imbalance of mitochondrial fission-fusion dynamics.
��ٻ, ��ΰΰ, �Ž���. ��κ��ͨ�������������-�ں�ʧ����Ƹ���A���յ���ADģ��С��ѧϰ�����ϰ�[J]. �й�ҩѧ��־, 2019, 54(9): 703-710.
WANG Qian, QIN Wei-wei, ZHANG Jie-wen. Effect of Ferulic Acid on Learning and Memory Impairment by the Repairing of Mitochondrial Fission-Fusion Imbalance in AD Mice. Chinese Pharmaceutical Journal, 2019, 54(9): 703-710.
SHEN Y, ZHANG Q, ZHAO S J, et al. Common pathological mechanism of Alzheimer��s disease and Parkinson��s disease. Chin Arch Tradit Chin Med(�л���ҽҩѧ��), 2018, 37(2):319-322.
[2]
WANG Y P, ZHAI J B, ZHU F, et al. Prevalence of Alzheimer��s disease and its influencial factors among elderly people in communities. Chin J Public Health(���������), 2011, 27(7):827-828.
[3]
LONG Y X, TANG Y M, TANG L J, et al. Meta-analysis on major risk factors of Alzheimer��s disease in China. Chin Prev Med(�й�Ԥ��ҽѧ��־),2013, 14(1):59-63.
[4]
JAKKI S L, SENTHIL V, YASAM V R, et al. The blood brain barrier and its role in Alzheimer��s therapy: an overview . Curr Drug Targets, 2018, 19(2):155-169.
[5]
ZHANG G, WU J J, JIANG M, et al. Development of experiment on treating Alzheimer��s disease with traditional Chinese medicine. Chin J Exp Tradit Med Form(�й�ʵ�鷽��ѧ��־), 2014,20(6):217-222.
[6]
WANG Y, WANG X, YU S, et al. Effects of ferulic acid on oxidative stress and apoptosis related proteins in Alzheimer��s disease transgenic mice. Nat Prod Res Dev(��Ȼ�����о��뿪��), 2017, 29(5):762-766.
[7]
SCHMITZ T W, MUR M, AGHOURIAN M, et al. Longitudinal Alzheimer��s degeneration reflects the spatial topography of cholinergic basal forebrain projections. Cell Rep, 2018, 24(1):38-46.
[8]
WU J L, SHEN M M, YANG S X, et al. Inhibition effect of ferulic acid on inflammation of microglia. Chin Pharmacol Bull(�й�ҩ��ѧͨ��), 2015, 31(1):97-102.
[9]
LUO Y, ZHAO H P, ZHANG J, et al. Effect of ferulic acid on learning and memoryimpairments of vasculardementia rats and its mechanism of action. Acta Pharm Sin(ҩѧѧ��), 2012, 47(2):256-260.
[10]
MORI T, KOYAMA N, TAN J, et al. Combination therapy with octyl gallate and ferulic acid improves cognition and neurodegeneration in a transgenic mouse model of Alzheimer��s disease. J Biol Chem, 2017, 292(27):11310-11325.
[11]
AKHTER H, HUANG W T, VAN GROEN T, et al. A small molecule inhibitor of plasminogen activator inhibitor-1 reduces brain amyloid-�� load and improves memory in an animal model of Alzheimer��s disease. J Alzheimers Dis, 2018, 64(2):447-457.
[12]
FURCILA D, DEFELIPE J, ALONSO-NANCLARES L. A study of amyloid-�� and phosphotau in plaques and neurons in the hippocampus of Alzheimer��s disease patients. J Alzheimers Dis, 2018, 64(2):417-435.
[13]
XU L L, SHEN Y, WANG X, et al. Mitochondrial dynamics changes with age in an APPsw/PS1dE9 mouse model of Alzheimer��s disease. Neuroreport, 2017, 28(4):222-228.
[14]
JOSHI A U, SAW N L, SHAMLOO M, et al. Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer��s disease. Oncotarget, 2017, 9(5):6128-6143.
[15]
GUO M Y, SHANG L, HU Y Y, et al. The role of Cdk5-mediated Drp1 phosphorylation in A��1-42 induced mitochondrial fission and neuronal apoptosis. J Cell Biochem, 2018, 119(6):4815-4825.
[16]
LEE S Y, CHO W H, LEE Y S, et al. Impact of chronic stress on the spatial learning and GR-PKAc-NF-��B signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol, 2018, 55(5):3976-3989.
[17]
KURUVA C S, MANCZAK M, YIN X, et al. Aqua-soluble DDQ reduces the levels of Drp1 and A�� and inhibits abnormal interactions between A�� and Drp1 and protects Alzheimer��s disease neurons from A��- and Drp1-induced mitochondrial and synaptic toxicities. Hum Mol Genet, 2017, 26(17):3375-3395.
[18]
JIANG S, NANDY P, WANG W, et al. Mfn2 ablation causes an oxidative stress response and eventual neuronal death in the hippocampus and cortex. Mol Neurodegener, 2018, 13(1):5.
2019, Vol. 54 
