Astrocytic p-connexin 43 regulates neuronal autophagy in the hippocampus following traumatic brain injury in rats.
Gap junctions are conductive channels formed by membrane proteins termed connexins, which permit the intercellular exchange of metabolites, ions and small molecules. Previous data demonstrated that traumatic brain injury (TBI) activates autophagy and increases microtubule‑associated protein 1 light chain 3 (LC3) immunostaining predominantly in neurons. Although previous studies have identified several extracellular factors that modulate LC3 expression, knowledge of the regulatory network controlling LC3 in health and disease remains incomplete. The aim of the present study was to assess whether gap junctions control the in vivo expression of LC3 in TBI. Using a modified weight‑drop device, adult male Sprague‑Dawley rats (weight, 350‑375 g) were subjected to TBI. Phosphorylated gap junction protein levels and LC3‑Ⅱ levels were quantified using western blot analysis. The spatial distribution of immunoreactivity for phosphorylated connexin 43 (p‑CX43) and LC3‑Ⅱ was analyzed by immunofluorescence. The results showed that p‑CX43 expression in the hippocampus reached a maximum level 6 h following injury. In addition, the immunoreactivity of p‑CX43 was localized in the astrocytes surrounding pyramidal neurons. The LC3‑Ⅱ protein content remained at high levels 24 h following injury. Double immunolabeling demonstrated that LC3‑II dots colocalized with the hippocampus pyramidal neurons. Furthermore, inhibition of p‑CX43 reduced TBI‑induced autophagy, according to western blot analysis. As astrocytic gap junction coupling is affected in various forms of brain injury, the results suggest that point gap junctions/connexins are important regulators of autophagy in the hippocampal neurons following TBI.
Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Li-Qian
LQ
Sun
Jun-Ling
JL
Gao
Chang-Men
CM
Cui
Ying
Y
Cui
Xiao-Bin
XB
Jing
Man-Man
MM
Zhao
Yong-Chao
YC
Wang
Yan-Xia
YX
Tian
Kai-Jie
KJ
Wang
Jian-Zhong
JZ
Cui
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001343:Autophagy; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002229:Carbenoxolone / Q000494:pharmacology / Q000627:therapeutic use; D018031:Connexin 43 / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002229:Carbenoxolone; D018031:Connexin 43; D006635:Histamine H2 Antagonists; D008869:Microtubule-Associated Proteins; C526109:Anxa3 protein, rat