Inhibition of Lats1/p-YAP1 pathway mitigates neuronal apoptosis and neurological deficits in a rat model of traumatic brain injury

CNS Neurosci Ther. 2018 Oct;24(10):906-916. doi: 10.1111/cns.12833. Epub 2018 Feb 27.

Abstract

Aims: To investigate the roles of Lats1/p-YAP1 pathway in TBI-induced neuronal apoptosis and neurological deficits in rats.

Results: We found that Lats1 and YAP1 were expressed in cerebral cortex neurons of Sprague-Dawley rats, and the phosphorylation levels of Lats1 and YAP1 in injured regions were significantly increased after TBI. Furthermore, inhibition of Lats1 not only decreased the level of p-YAP1, but also attenuated neuronal apoptosis and neurological impairment.

Conclusions: Our work demonstrates that inhibition of Lats1/p-YAP1 pathway mitigates neuronal apoptosis and neurological deficits in a rat model of TBI.

Keywords: Lats1; YAP1; neurological deficit; neuronal apoptosis; traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Brain Edema / etiology
  • Brain Edema / pathology
  • Brain Injuries, Traumatic / complications*
  • Brain Injuries, Traumatic / pathology*
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Fluoresceins / metabolism
  • In Situ Nick-End Labeling
  • Male
  • Nervous System Diseases / etiology*
  • Neurons / drug effects
  • Neurons / pathology*
  • Neurons / physiology
  • Phosphopyruvate Hydratase / metabolism
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Signal Detection, Psychological / drug effects
  • Signal Detection, Psychological / physiology*
  • Time Factors
  • YAP-Signaling Proteins

Substances

  • Apoptosis Regulatory Proteins
  • Fluoresceins
  • RNA, Small Interfering
  • YAP-Signaling Proteins
  • Yap1 protein, rat
  • fluoro jade
  • Lats1 protein, rat
  • Protein Serine-Threonine Kinases
  • Caspase 3
  • Phosphopyruvate Hydratase