PMID- 26463268 OWN - NLM STAT- MEDLINE DCOM- 20160815 LR - 20220408 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 5 DP - 2015 Oct 14 TI - Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models. PG - 15032 LID - 10.1038/srep15032 [doi] LID - 15032 AB - Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models. FAU - Wu, Yuanyuan AU - Wu Y AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Department of Anesthesiology, Wuhan Children Hospital, Wuhan 430030 China. FAU - Luo, Xiaobin AU - Luo X AD - Shenzhen/Guangzhou Kai-Tuo Biotech, Guangzhou, 510800, China. FAU - Liu, Xinhua AU - Liu X AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Liu, Deyi AU - Liu D AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Xiong AU - Wang X AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Guo, Ziyuan AU - Guo Z AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhu, Lingqiang AU - Zhu L AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Tian, Qing AU - Tian Q AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yang, Xifei AU - Yang X AD - Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China. FAU - Wang, Jian-Zhi AU - Wang JZ AD - Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - Co-innovation Center of Neuroregeneration, Nantong 226001, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151014 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Drug Combinations) RN - 0 (Gene Products, tat) RN - 0 (Nerve Tissue Proteins) RN - 0 (Recombinant Fusion Proteins) RN - DL48G20X8X (Scopolamine) SB - IM MH - Alzheimer Disease/chemically induced/*drug therapy/*physiopathology MH - Amyloid beta-Protein Precursor MH - Animals MH - Blood-Brain Barrier/metabolism MH - Brain-Derived Neurotrophic Factor/*administration & dosage/genetics/pharmacokinetics MH - Cognition/drug effects MH - Cognition Disorders/chemically induced/*physiopathology/*prevention & control MH - Disease Models, Animal MH - Drug Combinations MH - Gene Products, tat/*administration & dosage/genetics/pharmacokinetics MH - Injections, Intraperitoneal MH - Male MH - Mice MH - Mice, Transgenic MH - Nerve Tissue Proteins/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Recombinant Fusion Proteins/administration & dosage/genetics MH - Scopolamine MH - Treatment Outcome PMC - PMC4604491 EDAT- 2015/10/16 06:00 MHDA- 2016/08/16 06:00 PMCR- 2015/10/14 CRDT- 2015/10/15 06:00 PHST- 2015/05/28 00:00 [received] PHST- 2015/09/02 00:00 [accepted] PHST- 2015/10/15 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2016/08/16 06:00 [medline] PHST- 2015/10/14 00:00 [pmc-release] AID - srep15032 [pii] AID - 10.1038/srep15032 [doi] PST - epublish SO - Sci Rep. 2015 Oct 14;5:15032. doi: 10.1038/srep15032.