title: Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats.
abstract: Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.
authors: Department of Orthopaedics, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors: Peifu
authors: P
authors: Tang
authors: Hongping
authors: H
authors: Hou
authors: Licheng
authors: L
authors: Zhang
authors: Xia
authors: X
authors: Lan
authors: Zhi
authors: Z
authors: Mao
authors: Daohong
authors: D
authors: Liu
authors: Chunqing
authors: C
authors: He
authors: Hailong
authors: H
authors: Du
authors: Lihai
authors: L
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000517:prevention & control; D013904:Thoracic Vertebrae
chemical_list: D020123:Sirolimus
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