Abstract Title

Alteration of mammalian target of rapamycin signaling pathways in an In Vitro model of repetitive mild traumatic brain injury

Disciplines

Medical Neurobiology | Medicine and Health Sciences | Neurosciences

Abstract

Repetitive mild or concussive traumatic brain injury (rmTBI) can cause substantial neurologic impairment and is a major cause of disability in the US. The regulatory mechanisms that underlie repair and remodeling of neurons at the molecular level after rmTBI are poorly understood. Of particular interest is the involvement of the protein, mammalian target of rapamycin (mTOR). mTOR helps in controlling mRNA translation initiation, cellular and synaptic growth, repair and neuroplasticity. Here we utilized an in vitro model of mild repetitive stretch induced injury to investigate the effect of mechanical insult on both the gene and protein expression of mTOR and its downstream signaling components in cultured human SHSY5Y neuronal cell line. We found that mTOR, and eIF4B phosphorylation levels were significantly increased at 24 hours post injury at both the transcript and protein levels. Additionally, cell death increased significantly post injury as evidenced by increase in levels of LDH. Our findings indicate that changes in mTOR and its downstream proteins may play an integral role after rmTBI and may provide promising new strategies for repair, regrowth and remodeling of neurons.

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Alteration of mammalian target of rapamycin signaling pathways in an In Vitro model of repetitive mild traumatic brain injury

Repetitive mild or concussive traumatic brain injury (rmTBI) can cause substantial neurologic impairment and is a major cause of disability in the US. The regulatory mechanisms that underlie repair and remodeling of neurons at the molecular level after rmTBI are poorly understood. Of particular interest is the involvement of the protein, mammalian target of rapamycin (mTOR). mTOR helps in controlling mRNA translation initiation, cellular and synaptic growth, repair and neuroplasticity. Here we utilized an in vitro model of mild repetitive stretch induced injury to investigate the effect of mechanical insult on both the gene and protein expression of mTOR and its downstream signaling components in cultured human SHSY5Y neuronal cell line. We found that mTOR, and eIF4B phosphorylation levels were significantly increased at 24 hours post injury at both the transcript and protein levels. Additionally, cell death increased significantly post injury as evidenced by increase in levels of LDH. Our findings indicate that changes in mTOR and its downstream proteins may play an integral role after rmTBI and may provide promising new strategies for repair, regrowth and remodeling of neurons.