Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke.
In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3(+/+), but not in galectin-3(-/-), mice. In vitro we show that serum from galectin-3(+/+), but not from galectin-3(-/-), mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4(-/-) mice were unaffected. Further purified galectin-3 (10(-6) M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3(+/+) pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.
Neurogastroenterology unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Xiaowen
X
Cheng
Neuroinflammation unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Antonio
A
Boza-Serrano
Neurogastroenterology unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Michelle Foldschak
MF
Turesson
Neuroinflammation unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Tomas
T
Deierborg
Neurogastroenterology unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Eva
E
Ekblad
Neurogastroenterology unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Ulrikke
U
Voss
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000294:innervation / Q000503:physiopathology; D004195:Disease Models, Animal; D037502:Galectin 3 / Q000378:metabolism*; D007082:Ileum / Q000294:innervation / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D015398:Signal Transduction; D020521:Stroke / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
D055372:AMP-Activated Protein Kinases; D037502:Galectin 3; D020930:MAP Kinase Kinase Kinases; D051197:Toll-Like Receptor 4; D000099151:MAP Kinase Kinase Kinase 7; C485095:Lgals3 protein, mouse; C493487:Tlr4 protein, mouse