title: [Gly14]-Humanin reduces histopathology and improves functional outcome after traumatic brain injury in mice.
abstract: Humanin (HN) has been identified as an endogenous peptide that inhibited AD-relevant neuronal cell death. HNG, a variant of HN in which the 14th amino acid serine was replaced with glycine, can reduce infarct volume and improve neurological deficits after ischemia/reperfusion injury. In this study, we aimed to examine the neuroprotective effect of HNG on traumatic brain injury (TBI) in mice and explored whether the protective effect was associated with regulating apoptosis and autophagy. Compared to vehicle-treated groups, mice administered HNG intracerebroventricularly (i.c.v.) prior to TBI had decreased cells with plasmalemma permeability in the injured cortex and hippocampus (48 h, P<0.01), reduced brain lesion volume (days 14 and 28, P<0.05), improved motor performance (days 1-4, P<0.05) and ameliorated performance in the Morris water maze test (days 11-13, P<0.05) post TBI. Reduced lesion volume (day 14, P<0.05) was also observed even when HNG was administered intraperitoneally (i.p.) at 1h and 2h post TBI, and minor amelioration in motor and Morris water maze test deficits was also observed. Immunoblotting results showed that HNG pretreatment (i.c.v.) reversed TBI-induced cleavage of cysteinyl aspartate-specific protease-3 and poly ADPribose-polymerase and decline of Bcl-2, suppressed LC3II, Beclin-1 and vacuolar sorting protein 34 activation and maintained p62 levels in the injured cortex and hippocampus post TBI (compared with vehicle). In conclusion, HNG treatment improved morphological and functional outcomes after TBI in mice and the protective effect of HNG against TBI may be associated with down-regulating apoptosis and autophagy.
authors.affiliation: Department of Forensic Science and Laboratory of Brain Injury, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Bao
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Dai
authors.forename: P
authors.initials: P
authors.lastname: Chang
authors.forename: W
authors.initials: W
authors.lastname: Dong
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C427211:humanin