PMID- 31658360
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20220531
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 177
IP  - 3
DP  - 2020 Feb
TI  - Neurotrophic interactions between neurons and astrocytes following 
      AAV1-Rheb(S16H) transduction in the hippocampus in vivo.
PG  - 668-686
LID - 10.1111/bph.14882 [doi]
AB  - BACKGROUND AND PURPOSE: We recently reported that AAV1-Rheb(S16H) transduction 
      could protect hippocampal neurons through the induction of brain-derived 
      neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear 
      how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces 
      neuroprotective effects in the hippocampus and whether its up-regulation 
      contributes to the enhance of a neuroprotective system in the adult brain. 
      EXPERIMENTAL APPROACH: To determine the presence of a neuroprotective system in 
      the hippocampus of patients with Alzheimer's disease (AD), we examined the levels 
      of glial fibrillary acidic protein, BDNF and ciliary neurotrophic factor (CNTF) 
      and their receptors, tropomyocin receptor kinase B (TrkB) and CNTF 
      receptor alpha(CNTFRalpha), in the hippocampus of AD patients. We also determined whether 
      AAV1-Rheb(S16H) transduction stimulates astroglial activation and whether 
      reactive astrocytes contribute to neuroprotection in models of hippocampal 
      neurotoxicity in vivo and in vitro. KEY RESULTS: AD patients may have a potential 
      neuroprotective system, demonstrated by increased levels of full-length TrkB and 
      CNTFRalpha in the hippocampus. Further AAV1-Rheb(S16H) transduction induced sustained 
      increases in the levels of full-length TrkB and CNTFRalpha in reactive astrocytes and 
      hippocampal neurons. Moreover, neuronal BDNF produced by Rheb(S16H) transduction 
      of hippocampal neurons induced reactive astrocytes, resulting in CNTF production 
      through the activation of astrocytic TrkB and the up-regulation of neuronal BDNF 
      and astrocytic CNTF which had synergistic effects on the survival of hippocampal 
      neurons in vivo. CONCLUSIONS AND IMPLICATIONS: The results demonstrated that 
      Rheb(S16H) transduction of hippocampal neurons could strengthen the 
      neuroprotective system and this intensified system may have a therapeutic value 
      against neurodegeneration in the adult brain.
CI  - (c) 2019 The Authors. British Journal of Pharmacology published by John Wiley & 
      Sons Ltd on behalf of British Pharmacological Society.
FAU - Jeon, Min-Tae
AU  - Jeon MT
AD  - School of Life Sciences, Kyungpook National University, Daegu, Korea.
AD  - BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 
      Korea.
FAU - Moon, Gyeong Joon
AU  - Moon GJ
AUID- ORCID: 0000-0002-2851-9563
AD  - School of Life Sciences, Kyungpook National University, Daegu, Korea.
AD  - BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 
      Korea.
FAU - Kim, Sehwan
AU  - Kim S
AD  - School of Life Sciences, Kyungpook National University, Daegu, Korea.
AD  - BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 
      Korea.
FAU - Choi, Minji
AU  - Choi M
AD  - Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 
      Seoul, Korea.
FAU - Oh, Yong-Seok
AU  - Oh YS
AUID- ORCID: 0000-0002-9039-2014
AD  - Department of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and 
      Technology, Daegu, Korea.
FAU - Kim, Dong Woon
AU  - Kim DW
AUID- ORCID: 0000-0001-7691-1394
AD  - Department of Anatomy, Brain Research Institute, Chungnam National University 
      School of Medicine, Daejeon, Korea.
FAU - Kim, Hyung-Jun
AU  - Kim HJ
AD  - Department of Neural Development and Disease, Department of Structure and 
      Function of Neural Network, Korea Brain Research Institute, Daegu, Korea.
FAU - Lee, Kea Joo
AU  - Lee KJ
AUID- ORCID: 0000-0002-1366-4709
AD  - Department of Neural Development and Disease, Department of Structure and 
      Function of Neural Network, Korea Brain Research Institute, Daegu, Korea.
FAU - Choe, Youngshik
AU  - Choe Y
AD  - Department of Neural Development and Disease, Department of Structure and 
      Function of Neural Network, Korea Brain Research Institute, Daegu, Korea.
FAU - Ha, Chang Man
AU  - Ha CM
AD  - Department of Neural Development and Disease, Department of Structure and 
      Function of Neural Network, Korea Brain Research Institute, Daegu, Korea.
FAU - Jang, Il-Sung
AU  - Jang IS
AD  - Department of Pharmacology, School of Dentistry, Kyungpook National University, 
      Daegu, Korea.
AD  - Brain Science and Engineering Institute, Kyungpook National University, Daegu, 
      Korea.
FAU - Nakamura, Michiko
AU  - Nakamura M
AD  - Brain Science and Engineering Institute, Kyungpook National University, Daegu, 
      Korea.
FAU - McLean, Catriona
AU  - McLean C
AD  - Victorian Brain Bank Network, Florey Institute of Neuroscience and Mental Health, 
      Parkville, Victoria, Australia.
AD  - Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, 
      Australia.
FAU - Chung, Won-Suk
AU  - Chung WS
AD  - Department of Biological Sciences, Korea Advanced Institute of Science and 
      Technology (KAIST), Daejeon, Korea.
FAU - Shin, Won-Ho
AU  - Shin WH
AD  - Predictive Model Research Center, Korea Institute of Toxicology, Daejeon, Korea.
FAU - Lee, Seok-Geun
AU  - Lee SG
AUID- ORCID: 0000-0002-0060-5777
AD  - Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 
      Seoul, Korea.
AD  - KHU-KIST Department of Converging Science and Technology, Kyung Hee University, 
      Seoul, Korea.
FAU - Kim, Sang Ryong
AU  - Kim SR
AUID- ORCID: 0000-0003-0299-1613
AD  - School of Life Sciences, Kyungpook National University, Daegu, Korea.
AD  - BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, 
      Korea.
AD  - Institute of Life Science and Biotechnology, Kyungpook National University, 
      Daegu, Korea.
AD  - Brain Science and Engineering Institute, Kyungpook National University, Daegu, 
      Korea.
LA  - eng
GR  - 18-BR-03-01/KBRI Research Program of the Ministry of Science, ICT & Future 
      Planning/International
GR  - 18-RB-03-03/KBRI Research Program of the Ministry of Science, ICT & Future 
      Planning/International
GR  - 18-BR-02-06/KBRI Research Program of the Ministry of Science, ICT & Future 
      Planning/International
GR  - HI15C1928/Ministry of Health & Welfare/International
GR  - HI14C1135/Ministry of Health & Welfare/International
GR  - NRF-2017R1D1A1B03032218/National Research Foundation of Korea/International
GR  - NRF-2017R1A2B4002675/National Research Foundation of Korea/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191227
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
SB  - IM
MH  - *Astrocytes/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Glial Fibrillary Acidic Protein
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Neurons/metabolism
MH  - *Neuroprotective Agents/pharmacology
MH  - Ras Homolog Enriched in Brain Protein/metabolism
PMC - PMC7012949
COIS- The authors declare no conflicts of interest.
EDAT- 2019/10/29 06:00
MHDA- 2021/06/22 06:00
PMCR- 2019/12/27
CRDT- 2019/10/29 06:00
PHST- 2019/03/11 00:00 [received]
PHST- 2019/09/16 00:00 [revised]
PHST- 2019/09/16 00:00 [accepted]
PHST- 2019/10/29 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/10/29 06:00 [entrez]
PHST- 2019/12/27 00:00 [pmc-release]
AID - BPH14882 [pii]
AID - 10.1111/bph.14882 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2020 Feb;177(3):668-686. doi: 10.1111/bph.14882. Epub 2019 Dec 
      27.