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Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury.
J Cereb Blood Flow Metab. 2007 May; 27(5):939-49.JC

Abstract

In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.

Authors+Show Affiliations

The Neurochemistry Laboratory of Brain Injury, Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16955078

Citation

Chen, Shaoyi, et al. "Alterations in Mammalian Target of Rapamycin Signaling Pathways After Traumatic Brain Injury." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 27, no. 5, 2007, pp. 939-49.
Chen S, Atkins CM, Liu CL, et al. Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury. J Cereb Blood Flow Metab. 2007;27(5):939-49.
Chen, S., Atkins, C. M., Liu, C. L., Alonso, O. F., Dietrich, W. D., & Hu, B. R. (2007). Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 27(5), 939-49.
Chen S, et al. Alterations in Mammalian Target of Rapamycin Signaling Pathways After Traumatic Brain Injury. J Cereb Blood Flow Metab. 2007;27(5):939-49. PubMed PMID: 16955078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury. AU - Chen,Shaoyi, AU - Atkins,Coleen M, AU - Liu,Chunli L, AU - Alonso,Ofelia F, AU - Dietrich,W Dalton, AU - Hu,Bingren R, Y1 - 2006/08/30/ PY - 2006/9/7/pubmed PY - 2007/5/23/medline PY - 2006/9/7/entrez SP - 939 EP - 49 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 27 IS - 5 N2 - In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI. SN - 0271-678X UR - https://www.unboundmedicine.com/medline/citation/16955078/Alterations_in_mammalian_target_of_rapamycin_signaling_pathways_after_traumatic_brain_injury_ L2 - https://journals.sagepub.com/doi/10.1038/sj.jcbfm.9600393?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -