Neurotropin reduces memory impairment and neuroinflammation via BDNF/NF-κB in a transgenic mouse model of Alzheimer’s disease

American Journal of Translational Research

Shengnuo Fan¹  Wenli Fang²  Yuqiu Zheng³  Wang Liao⁴  Jianjun Chen⁵  Xingmei Zhang⁶  Xiaoyu Chen⁷  Xueling Weng⁸  Xiaoyun Huang⁹ 

[1] Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Karolinska Sjukhuset, Sweden;Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China;Department of Neurology, The Affiliated Houjie Hospital, Guangdong Medical University, Dongguan 523945, Guangdong, China;Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA;Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510120, Guangdong, China;Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China;Medicine School, Shenzhen University, Shenzhen 518060, Guangdong, China;Peoples Hospital of Zhongshan City, Zhongshan 528403, Guangdong, China;Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China

关键词: Alzheimer’;    s disease;    neurotropin;    neuroinflammation;    brain derived neurotrophic factor;    memory impairment;    NF-κ;    B;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Alzheimer’s disease (AD) is a devastating neurodegenerative disease with limited treatments and no cure. Neurotropin (NTP) is an analgesic drug widely prescribed for neuropathic pain. Increasing evidence suggests that NTP may also protect against neurodegeneration, but NTP’s treatment potential against memory impairments of AD remains to be explored. APP/PS1 mice, which model AD, were given NTP for three months then cognitively tested with the Morris water maze. Their Aβ burden, microglial and astrocytic activation, and BDNF levels were compared to untreated controls using immunofluorescent staining. Expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and NF-κB pathway related proteins (p65 and IκB-α) were examined by ELISA or Western blots in vivo and in vitro in the microglia cell line. Lastly, BV-2 cells were pre-treated with the selective BDNF inhibitor ANA-12 and with NTP to examine mechanistic pathways. Taken together, NTP treatment reduced cognitive impairment, Aβ deposits, and glial activation in cortex and hippocampus APP/PS1 mice. IL-1β, IL-6 and TNF-α also decreased after NTP treatment in vivo and in vitro, and BDNF levels rose. Also, NTP reduced p65 and IκB-α activation and the effect of NTP on pro-inflammatory cytokines and NF-κB pathway related proteins was abolished by BDNF inhibitor. Our results indicate that NTP reduces neuroinflammation and improves the cognitive deficits in APP/PS1 mice possibly via BDNF/NF-κB pathway. NTP may be a new promising drug candidate for patients with AD.

【 授权许可】

CC BY-NC