PMID- 31165005
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2152-5250 (Print)
IS  - 2152-5250 (Electronic)
IS  - 2152-5250 (Linking)
VI  - 10
IP  - 3
DP  - 2019 Jun
TI  - BDNF Alleviates Neuroinflammation in the Hippocampus of Type 1 Diabetic Mice via 
      Blocking the Aberrant HMGB1/RAGE/NF-kappaB Pathway.
PG  - 611-625
LID - 10.14336/AD.2018.0707 [doi]
AB  - Diabetes is a systemic disease that can cause brain damage such as synaptic 
      impairments in the hippocampus, which is partly because of neuroinflammation 
      induced by hyperglycemia. Brain-derived neurotrophic factor (BDNF) is essential 
      in modulating neuroplasticity. Its role in anti-inflammation in diabetes is 
      largely unknown. In the present study, we investigated the effects of BDNF 
      overexpression on reducing neuroinflammation and the underlying mechanism in mice 
      with type 1 diabetes induced by streptozotocin (STZ). Animals were 
      stereotactically microinjected in the hippocampus with recombinant 
      adeno-associated virus (AAV) expressing BDNF or EGFP. After virus infection, four 
      groups of mice, the EGFP+STZ, BDNF+STZ, EGFP Control and BDNF Control groups, 
      received STZ or vehicle treatment as indicated. Three weeks later brain tissues 
      were collected. We found that BDNF overexpression in the hippocampus 
      significantly rescued STZ-induced decreases in mRNA and protein expression of two 
      synaptic plasticity markers, spinophilin and synaptophysin. More interestingly, 
      BDNF inhibited hyperglycemia-induced microglial activation and reduced elevated 
      levels of inflammatory factors (TNF-alpha, IL-6). BDNF blocked the increase in HMGB1 
      levels and specifically, in levels of one of the HMGB1 receptors, RAGE. 
      Downstream of HMGB1/RAGE, the increase in the protein level of phosphorylated 
      NF-kappaB was also reversed by BDNF in STZ-treated mice. These results show that BDNF 
      overexpression reduces neuroinflammation in the hippocampus of type 1 diabetic 
      mice and suggest that the HMGB1/RAGE/NF-kappaB signaling pathway may contribute to 
      alleviation of neuroinflammation by BDNF in diabetic mice.
FAU - Han, Rongrong
AU  - Han R
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Liu, Zeyue
AU  - Liu Z
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Sun, Nannan
AU  - Sun N
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Liu, Shu
AU  - Liu S
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Li, Lanlan
AU  - Li L
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Shen, Yan
AU  - Shen Y
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Xiu, Jianbo
AU  - Xiu J
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Xu, Qi
AU  - Xu Q
AD  - 1State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical 
      Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking 
      Union Medical College, Beijing, China.
AD  - 2Neuroscience center, Chinese Academy of Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20190601
PL  - United States
TA  - Aging Dis
JT  - Aging and disease
JID - 101540533
PMC - PMC6538223
OTO - NOTNLM
OT  - BDNF
OT  - HMGB1
OT  - RAGE
OT  - diabetes
OT  - neuroinflammation
EDAT- 2019/06/06 06:00
MHDA- 2019/06/06 06:01
PMCR- 2019/06/01
CRDT- 2019/06/06 06:00
PHST- 2018/03/28 00:00 [received]
PHST- 2018/06/07 00:00 [accepted]
PHST- 2019/06/06 06:00 [entrez]
PHST- 2019/06/06 06:00 [pubmed]
PHST- 2019/06/06 06:01 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - ad-10-3-611 [pii]
AID - 10.14336/AD.2018.0707 [doi]
PST - epublish
SO  - Aging Dis. 2019 Jun 1;10(3):611-625. doi: 10.14336/AD.2018.0707. eCollection 2019 
      Jun.