PMID- 36336009
OWN - NLM
STAT- MEDLINE
DCOM- 20221122
LR  - 20221122
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 936
DP  - 2022 Dec 5
TI  - Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced 
      neurotoxicity and cognitive deficits by inhibiting TLR4/NF-small ka, CyrillicB signaling in aged 
      mice.
PG  - 175360
LID - S0014-2999(22)00621-5 [pii]
LID - 10.1016/j.ejphar.2022.175360 [doi]
AB  - Neuroinflammation is thought to contribute to the onset and progression of 
      Alzheimer's disease (AD). Galectin-3 (Gal-3), the only member of the galectin 
      chimeric subfamily, is a key regulator of neuroinflammation and microglial 
      activation. However, the effects of Gal-3 inhibition in AD-related 
      neuroinflammation are unclear. Here, we investigated whether hippocampal Gal-3 
      knockdown alleviated lipopolysaccharide (LPS)-induced neurotoxicity and cognitive 
      deficits, as well as the underlying mechanisms. First, we bilaterally injected 
      aged mice (23 months old) with anti-Gal-3 short hairpin RNA into the hippocampus 
      dentate gyrus, followed by systemic LPS administration. To determine the effects 
      of hippocampal Gal-3 knockdown on neuroinflammatory response and neuronal 
      apoptosis, we assessed the effects of Gal-3 silencing on the levels of 
      pro-inflammatory cytokines, microglial activation, and apoptosis in the 
      hippocampus of LPS-exposed aged mice. Behavioral tests were used to access the 
      cognitive function of the mice. To explore the potential signaling, protein 
      extracts from the brains of mice were subjected to analyze the expression levels 
      of key molecules (including Toll-like receptor 4 (TLR4), myeloid differentiation 
      factor 88, and nuclear transcription factor-kappaB (NF-kappaB) p65) of the TLR4/NF-small ka, CyrillicB 
      pathway, and BV2 cells were pretreated with TLR4 inhibitor or NF-kappaB inhibitor 
      before Gal-3 stimulation. These analyses showed that hippocampal Gal-3 knockdown 
      attenuated neuroinflammation and neuronal apoptosis in the hippocampus of 
      LPS-challenged aged mice, and this was associated with improved cognitive 
      function. Hippocampal Gal-3 knockdown may protect against LPS-induced 
      neurotoxicity by inhibiting the TLR4/NF-small ka, CyrillicB pathway. Our findings highlight Gal-3 
      as a potential therapeutic target against AD-associated neuroinflammation.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Chen, Fang
AU  - Chen F
AD  - Department of Pharmacy, The First Affiliated Hospital of Xiamen University, 
      Xiamen, 361003, China.
FAU - Wu, Xiaofeng
AU  - Wu X
AD  - Department of Pharmacy, The First Affiliated Hospital of Xiamen University, 
      Xiamen, 361003, China.
FAU - Yang, Jiayong
AU  - Yang J
AD  - Department of Pharmacy, The First Affiliated Hospital of Xiamen University, 
      Xiamen, 361003, China.
FAU - Yu, Xuben
AU  - Yu X
AD  - Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, 325000, China.
FAU - Liu, Bili
AU  - Liu B
AD  - Department of Pharmacy, The First Affiliated Hospital of Xiamen University, 
      Xiamen, 361003, China. Electronic address: 3079158007@qq.com.
FAU - Yan, Zhiwen
AU  - Yan Z
AD  - Department of Pharmacy, The First Affiliated Hospital of Xiamen University, 
      Xiamen, 361003, China. Electronic address: yzwfirst@xmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221104
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (NF-kappa B)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Galectin 3)
RN  - 0 (Galectins)
RN  - 0 (Tlr4 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Toll-Like Receptor 4/genetics
MH  - NF-kappa B
MH  - Lipopolysaccharides/toxicity
MH  - Galectin 3/genetics
MH  - Galectins
MH  - Hippocampus
MH  - *Neurotoxicity Syndromes
MH  - Cognition
MH  - *Alzheimer Disease
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Cognitive deficits
OT  - Galectin-3
OT  - Lipopolysaccharide
OT  - Neuroinflammation
COIS- Declaration of competing interest The authors declare that they have no conflict 
      of interest.
EDAT- 2022/11/07 06:00
MHDA- 2022/11/23 06:00
CRDT- 2022/11/06 19:33
PHST- 2022/04/19 00:00 [received]
PHST- 2022/10/31 00:00 [revised]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/11/07 06:00 [pubmed]
PHST- 2022/11/23 06:00 [medline]
PHST- 2022/11/06 19:33 [entrez]
AID - S0014-2999(22)00621-5 [pii]
AID - 10.1016/j.ejphar.2022.175360 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2022 Dec 5;936:175360. doi: 10.1016/j.ejphar.2022.175360. Epub 
      2022 Nov 4.