title: Autophagy Modulation by Lanthionine Ketimine Ethyl Ester Improves Long-Term Outcome after Central Fluid Percussion Injury in the Mouse.
abstract: Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. Obstruction of the autophagic process has been noted after brain injury, and rapamycin, a drug used to stimulate autophagy, has demonstrated positive effects in brain injury models. The optimization of drugs to promote beneficial autophagy without negative side effects could be used to attenuate traumatic brain injury and promote improved outcome. Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 × TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation.
authors.affiliation: 1 Department of Pathology, University of Toledo Health Science Campus , Toledo, Ohio.|2 Department of Neurosciences, University of Toledo Health Science Campus , Toledo, Ohio.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hensley
authors.affiliation: 4 Veterans Administration-Greater Los Angeles Healthcare System , Los Angeles, California.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Poteshkina
authors.affiliation: 4 Veterans Administration-Greater Los Angeles Healthcare System , Los Angeles, California.
authors.forename: Ming F
authors.initials: MF
authors.lastname: Johnson
authors.affiliation: 4 Veterans Administration-Greater Los Angeles Healthcare System , Los Angeles, California.
authors.forename: Pirooz
authors.initials: P
authors.lastname: Eslami
authors.affiliation: 3 P2D Bioscience, Inc. , Cincinnati, Ohio.
authors.forename: S Prasad
authors.initials: SP
authors.lastname: Gabbita
authors.affiliation: 1 Department of Pathology, University of Toledo Health Science Campus , Toledo, Ohio.
authors.forename: Alexandar M
authors.initials: AM
authors.lastname: Hristov
authors.affiliation: 1 Department of Pathology, University of Toledo Health Science Campus , Toledo, Ohio.
authors.forename: Kalina M
authors.initials: KM
authors.lastname: Venkova-Hristova
authors.affiliation: 4 Veterans Administration-Greater Los Angeles Healthcare System , Los Angeles, California.|5 Department of Medicine, David Geffen School of Medicine at UCLA , Los Angeles, California.
authors.forename: Marni E
authors.initials: ME
authors.lastname: Harris-White
mesh_terms: D000603:Amino Acids, Sulfur / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D020833:Diffuse Axonal Injury / Q000188:drug therapy*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000603:Amino Acids, Sulfur; C035499:lanthionine ketimine
keywords: autophagy; behavior; diffuse axon injury; pathology