title: Lithium enhances axonal regeneration in peripheral nerve by inhibiting glycogen synthase kinase 3β activation.
abstract: Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN) is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS.
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau.
authors: Huanxing
authors: H
authors: Su
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Qiuju
authors: Q
authors: Yuan
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Dajiang
authors: D
authors: Qin
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Xiaoying
authors: X
authors: Yang
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Wai-Man
authors: 0000-0001-5007-9181
authors: WM
authors: Wong
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong ; GHM Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
authors: Kwok-Fai
authors: KF
authors: So
authors: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong ; GHM Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
authors: Wutian
authors: W
authors: Wu
mesh_terms: D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008094:Lithium / Q000494:pharmacology*; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D010525:Peripheral Nerves / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000201:enzymology / Q000293:injuries
chemical_list: D004791:Enzyme Inhibitors; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3