PMID- 37503724
OWN - NLM
STAT- MEDLINE
DCOM- 20230901
LR  - 20230901
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Linking)
VI  - 37
IP  - 8
DP  - 2023 Aug
TI  - Histone Deacetylase 3 Inhibition Ameliorates Microglia-Mediated 
      Neuro-Inflammation Via the SIRT1/Nrf2 Pathway After Traumatic Spinal Cord Injury.
PG  - 503-518
LID - 10.1177/15459683231183716 [doi]
AB  - BACKGROUND: Microglial-induced inflammation plays a crucial role in the 
      pathophysiological process of nervous system injury, however, still lacks 
      effective therapeutic agents. Previously, we discovered that the inhibition of 
      histone deacetylase 3 (HDAC3) exerts anti-inflammatory effects after traumatic 
      spinal cord injury (SCI), whereas little is known about its underlying mechanism. 
      Therefore, the present study aimed to explore the effects and potential 
      mechanisms of HDAC3 on neuroinflammation and microglial function. METHODS: Rats 
      were randomized into 4 groups: sham group, SCI group, SCI + vehicle group, and 
      SCI + RGF966 group. To examine the effect of HDAC3 on neurological deficit after 
      SCI, we gathered data using the Basso Beattie Bresnahan locomotion scale, the 
      inclined plane test, the blood-spinal cord barrier, junction protein expression, 
      and Nissl staining. We also evaluated microglial activation and inflammatory 
      factor levels. Immunofluorescence analysis, immunohistochemical analysis, western 
      blotting, and quantitative real-time polymerase chain reaction were performed to 
      examine the regulation of the Sirtuin 1 (SIRT1)/nuclear factor-erythroid 
      2-related factor 2 (Nrf2) pathway. RESULTS: The results showed that HDAC3 
      inhibition significantly ameliorated Basso-Beattie-Bresnahan (BBB) permeability, 
      brain edema, and improved neurological functions and junction protein levels. 
      Additionally, HDAC3 inhibition significantly inhibited microglial activation, 
      thereby reducing the levels of SCI-induced pro-inflammatory factors. Moreover, 
      HDAC3 inhibition dramatically enhanced the expression of SIRT1 and increased both 
      Nrf2 nuclear accumulation and transcriptional activity, thereby increasing 
      downstream heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1 expression. 
      CONCLUSIONS: The results of this study suggest that HDAC3 inhibition protects the 
      spinal cord from injury following SCI by inhibiting SCI-induced microglial 
      activation and the subsequent inflammatory response via SIRT1/Nrf2 signaling 
      pathway, highlighting HDAC3 as a potential therapeutic target for the treatment 
      of SCI.
FAU - Chen, Shoubo
AU  - Chen S
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Fujian Medical 
      University, Quanzhou, Fujian Province, China.
FAU - Ye, Jingfang
AU  - Ye J
AD  - Department of Nursing Faculty, Quanzhou Medical College, Quanzhou, Fujian 
      Province, China.
FAU - Wu, Guozhong
AU  - Wu G
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Fujian Medical 
      University, Quanzhou, Fujian Province, China.
FAU - Shi, Jinnan
AU  - Shi J
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Fujian Medical 
      University, Quanzhou, Fujian Province, China.
FAU - Li, Xiang
AU  - Li X
AD  - Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu Province, China.
FAU - Chen, Xiangrong
AU  - Chen X
AUID- ORCID: 0000-0001-6390-3328
AD  - Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical 
      University, Quanzhou, Fujian Province, China.
FAU - Wu, Wenhua
AU  - Wu W
AD  - Department of Orthopaedics, The Second Affiliated Hospital, Fujian Medical 
      University, Quanzhou, Fujian Province, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230728
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
RN  - EC 3.5.1.98 (histone deacetylase 3)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - 0 (Histone Deacetylase Inhibitors)
SB  - IM
MH  - Animals
MH  - Rats
MH  - Inflammation/drug therapy/metabolism
MH  - Microglia/metabolism
MH  - NF-E2-Related Factor 2
MH  - Rats, Sprague-Dawley
MH  - *Sirtuin 1/metabolism
MH  - Spinal Cord
MH  - *Spinal Cord Injuries/complications/drug therapy/metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
OTO - NOTNLM
OT  - HDAC3
OT  - SIRT1/Nrf2
OT  - microglia
OT  - neuroinflammation
OT  - traumatic spinal cord
EDAT- 2023/07/28 06:43
MHDA- 2023/08/28 06:42
CRDT- 2023/07/28 05:53
PHST- 2023/08/28 06:42 [medline]
PHST- 2023/07/28 06:43 [pubmed]
PHST- 2023/07/28 05:53 [entrez]
AID - 10.1177/15459683231183716 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2023 Aug;37(8):503-518. doi: 
      10.1177/15459683231183716. Epub 2023 Jul 28.